Fukuyama Group - Group Meeting Problems

2001/08/22

1
O 1) SOCl2, benzene; CN
hν Et3N, allyl amine
Cl carboxylic acid
H2O C10H12O2 2) PPh3, CCl4
acetone Et3N, CH3CN
O *
*) as acid scavenger

cat. Pd (0)
2 HO
Et3B (2.4 eq)
Et3N (1.2 eq) OH
OHC LiCl (1.0 eq)
+
THF
rt
HO

1) NaNO2 3) liq NH3

3 6 N HCl CH3CN
H2NOC CONH2 –45 °C to rt 45 °C NC CN
2) N 4) 250 °C, neat
H 2N N N H2N
Bn N N
H Bn
POCl3, Et3N
CH3CN

4 CH2CH2OCOPh
O O
hν (pyrex) HO Ph Ph
+ OMe
OMe
MeOH H

major minor

5
COOH
N O 1) CF3COCH3, NaHCO3, Oxone®
CH3CN-H2O, rt, pH7-7.5

2) 5% NaOH aq, MeOH O2N

100 °C, 12 h
O 2N 88%
 Fukuyama Group - Group Meeting Problems
08/29/2001

1
Me 1. TFAA, Py N
Ph N CO2H Ph COCF3
2. H NH2 N
O Me
NH·HCl
K2CO3, DMF
70 °C

2 MeO O PdI2 (0.2 mol%) MeO O CO2Me

KI (2 mol%)
CO/air (3:1, 600 psi )
CO2Me
MeOH
O 110 °C O

Hint: active catalyst = K2PdI4

3 3) BuLi, THF
OH O
1) NBS –78 °C to rt

2) NaH, TsCl 4) TMSCl (3 eq.), NaI (3 eq.)

CH3CN, rt

4
1. CO2Et
Br
NOH
Na2CO3 CN
2. aq. NaOH, 20 °C OH
3. 150 °C

MeO O CO2Me OMe CO Me

toluene O 2
reflux A
N
O A
N 30 h, 74%
OH O
(C6H8O2)

A : transient intermediate
 Fukuyama Group - Group Meeting Problems
09/05/2001

1
1) NaCN, DMSO, 130 °C
OAc
2) 0.5 mol% [Rh(CO)2Cl]2
toluene, 110 °C, 30 min
CO2Me OBn 93% H
BnO

2
OH
Br Br t-BuLi (5.5 eq), Et2O, –78 °C;
TMEDA, –78 °C to rt; Ph
Ph
PhCOCOPh OH
N N
Ph Ph

3
LTA (1.5 eq) O
CO (105 atm)
OH O
benzene, 80 °C
63%

4 O O
O O
Cu powder 1N HCl
+
PhH THF
reflux 65 °C
3.5 h 1h
N2 O O
O
9 : 1

5 n-Bu CO2Et t-BuLi (4 eq)

A
Br Br THF
–78 °C

n-Bu
O 1) A
THF, –78 °C CO2Et
CO2Et
+
2) H (silica gel)
benzene, reflux H
 Fukuyama Group - Group Meeting Problems
09/12/2001

O
1 n-BuLi
THF, –78 °C, 20 min;
HO
O
O then O

· N
O
F3C CF3 F3C

OH OH –78 °C to –30 °C, 1 hr;

then HCl / HFIP-TFE 78% (86%ee)
HFIP TFE
–78 °C to rt

2 CH2N2, Et2O
0 °C, 2 h;
evap; 1) LAH, Et2O, 0 °C H H
H H C13H13ClO
Cl cyclopentadiene (10 eq*) 2) KH (5 eq*), THF H CHO
O Cl Et3N (3 eq*) 0 °C to rt
TFE /Et2O (1 : 1) 74%
–78 °C to rt 76% (2 steps)
(two isomer 10.4 : 1)
TFE = trifluoroethanol * (*$"&')#1%)
3
O
OH CF3CO3H (8eq*) O
+
O
CF3CO2H, CH2Cl2

* (*$"&')#3%) OH

4
CO2Me
1. propargyl alcohol MeO2C
MeO2C OH PhI(OAc)2, CH3CN
Bu
Bu 2. Ph3SnH, Et3B
MeO2C O O
toluene
3. 1 M HCl, Et2O OH
O

5
Bn
R N
CHO
HN
N Bn
H benzoic acid, benzene
CO2Me reflux, 10 hr N R
H
CO2Me
79%
R=
 Fukuyama Group - Group Meeting Problems
09/19/2001

1 1) COCl2, DMAP, DMF

P 25 °C, 1 hr O P

N 2) NH2CH2CH2NH2, DMAP HN NH N
H CH2Cl2, 25 °C, 1 hr H
NO2 3) hν (lamp equipped with pyrex filter) NO2
THF

2 i-PrO O
tert-BuLi; ; i-PrO HO
OCH3
Br i-PrO O
i-PrO
H
Li ; aq NH4Cl O CH3
CH3

3
CO2Me
OH
H
1) SnCl4, toluene, –78 °C;
NaHCO3, toluene, 80 °C H Me
NO2 HO
2) H2, RaneyNi, MeOH
160 psi, rt H
Me NH
O

4
1) acetone, Ac2O 1) DIBAL, CH2Cl2 CHO
O ZnCl2, 48% 72%
C12H18O2
CO2Et 2) 2) (COCl)2, DMSO
PPh3Br Et3N, THF, 68%
n-BuLi, Et2O 3) DBU, CH2Cl2
85% 89%

5 OH
1) PhI(OAc)2 3) MeMgBr, CuI (cat.) O
CF3CH2OH 60% CO2Me
H 2) NaHCO3, MeOH 4) PhI(OAc)2, I2 N H
CO2H 0 °C to rt CH2Cl2, 80 % O
AcO Cbz
54% (2 steps)
NHCbz
 Fukuyama Group - Group Meeting Problems
09/26/2001

1 1) PPh3, THF;
H
O NaBH4, MeOH, rt
CO2Me O
O
N3 2) I2, CH2Cl2, Et2O, rt O N
MeO MeO H O
O
CHO

OAc
OAc
2 AgOTf OTBS
C CCH2OTBS CH3CN, 70 °C;
O NMe
BnMe3NCN N NMe
N rt
O
I
40%

3 1) PMe3 , Toluene , rt; p-Cl-C6H4

NH2 p-Cl-C6H4CHO Ph2C=C=O
N
N3 cat. AcOH 2) Pd/C , Toluene,
EtOH , reflux reflux N Ph

CH3
HO CH
4 1) Eu(fod)3 (10 mol%), toluene, 80 °C, 36 h, 84%
3

H3C
O 2) hν, Corex, 19 h, 79% H
H 3C
3) LiDBB, THF, –78 °C to 10 °C, 35 h, 57% CH3
CH3
LiDBB; lithium di-tert-butylbiphenylide
H 3C

5
1) MCPBA

2) (CF3CO)2O; N
N aq. Na2CO3
OH
 Fukuyama Group - Group Meeting Problems
10/03/2001

1 1) t-BuOCl, CH2Cl2, –70 °C;

O
EtO2C SMe –70 °C;
EtO2C

NH2 Et3N, –70 to 25 °C

N Me
2) Ra-Ni (xs), EtOH, 25 °C H

2
O2N O HC(NMe2)3 (5 eq) HN O

THF, reflux
N 5h N
H CH3 H CH3
80%

3
CHO
O
1,4-cyclohexadiene
PhCl, 150 °C OTBS
OTBS
54%
CO2Me
MeO2C

4
O
PhOH;
CHO HBF4 N
N

5
F
Me Me
N Et Me
N
N F
CHO

POCl3 Me N
Me Et
 Fukuyama Group - Group Meeting Problems
10/10/2001

1
10% KOH
N rt, overnight;

4 M HCl N
rt to 90 °C O
NO2 O

2
1) Bu3SnH, AIBN
benzene, ∆
O 2) MeLi HO
Si
Br Me3Si

3 Me Me
N I 3) 4N HCl H N
1) LDA reflux
+
N
2) HCl, PhH 4) NaBH4 H
SEM O rt, 2h N
CO2Me H
OH

4
OH
H H H
BnO 1) SOCl2, imidazole, CH2Cl2 BnO
–78 °C to rt, 81%
N NH2 N NH OPMB
Me 2) PhMgBr, THF/CH2Cl2, –50 °C; Me
H H
O OPMB (MeO)3P, MeOH, 50 °C O
BnO BnO
83%

1) t-BuOCl N
N SnCl4
N
H H
2) KHMDS N
H H
H CO2Me OTBDPS
MeO2C OTBDPS
 Fukuyama Group - Group Meeting Problems
10/17/2001

1 1)
O O
TIPSO
MeO OEt MeO CO2Et
t-BuOK, DMF, 105 °C
OTIPS
Me N3 2) hν, Vycor, CH3CN Me N
H
OMe OMe

2
O OLi O

TBS –80 to –30 °C

+
TMS THF TBSO
TMS
84%

3
1. Me2NNH2
2. MeI hν, Pyrex N
Ar O
+ ArCHO
O 3. NaH, THF 5% CH2=CHCN
O2 satd. MeCN CN
Ar = p-NO2C6H4

4
TBS SMe
O O
EtAlCl2
SMe
CH2Cl2
rt TBS
90%

O
NO2 HO Cl SmI2 CHCl3 HN

t-BuOK / t-BuOH (4 eq) rt O

 Fukuyama Group - Group Meeting Problems
10/24/2001

1 NC CN

NC CN
O hυ O
OH
O MeCN O

Me
2 Me CO2Et 1)
N
Me CO2Et
Ph H CO2Me
benzene, reflux,1hr
EtO2C CHO EtO2C N
N CO2Me
H 2) DMAD, benzene, rt, 2hr H MeN
Ph

3
O O
AIBN
Ph Ph
N Ph
xylene N
OH reflux, 35 min H

82%

OAc
4 1) LDA; TBDMSCl; 66 °C; H3O+
2) NH4Cl, EDCI, HOBt Cl
3) Cl3COCOCl, TEA
MeO NBoc
4) CHCl3, aq NaOH, cat. TEBAC
5) H2, PtO2; (Boc)2O, TEA i-PrO
MeO
6) AgBF4, 40 °C
O-i-Pr
EDCI; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
TEBAC; triethylbenzylammonium chloride

5 O
CO2Et 1) Ac2O, toluene, 50 °C
O
CO2Et
2) Ar'COCl, pyridine, 60 °C
Ar'
Ar N CO2H Ar N
3) AcOH, 90 °C H
H O
Cl
Ar = , Ar' =
O
 Fukuyama Group - Group Meeting Problems
10/31/2001

1
1) HOCH2SO3Na * R O
H2O, 40 °C
NH2 N SO3Na
BocHN BocHN
2) RCO2H
HOBt, DCC, Et3N
O
R= NH
N O

2 H
1) ArSO2N3 H
OEt i-Pr2NEt
O
N
N O O 2) Rh2(OAc)4 O
O OBn CH2Cl2 CO2Et

O O
3 Me
N Me S
N
N
O N N
NH2
0 °C , in SOCl2
A warmed to r.t. N
O N
H H H

TMSOTf
4 Ph

O benzene, CH2Cl2
reflux, 7 hr
Ph
98%

O OMe
5 Cp2ZrCl2, 2 eq n-BuLi
BnO OH
BnO OBn BF3•Et2O, THF
OBn BnO OBn
65%
 Fukuyama Group - Group Meeting Problems
11/07/2001

1
3) KOH
1) SCl2, pyridine MeOH, rt Me Me
2 Cl2NCO2Me
2) H3CHC CHCH2CH3 4) LAH NHMe
CHCl3 ether, reflux

2
3) t-BuOOH
1) I2, PhH Ti(O-i-Pr)4
HO
HO 2) m-CPBA CH2Cl2, 0 °C;
3) BF3•OEt2 OH Me2S, reflux H O

3
1) LDA, THF
–78 °C to rt; 1) NaBH4, Cu(acac)2
N Me o-NO2PhCOCl, Et3N; EtOH, rt
+ A
TMS 2) TFA, CH2Cl2 2) NaNO2, HCl, CuCl MeO H
I MeOH, 0 °C to rt NHBz
54%
74% (2 steps)

4
1.

O COCl
OMEM O
toluene, reflux, 64% O
SnBu3
2. BF3·OEt2, CH2Cl2
SO2Ph –78°C to rt, 62% O

5
Et
Et
HCO2H Me
N
N NMe rt
H Me OH N
OAc H
 Fukuyama Group - Group Meeting Problems
11/21/2001

I
1
1) TiCl4 1)
TMS OH
MeNO2 K2CO3 MeO2C
O CH2Cl2, acetone MeO2C
O O + H
A
2) LHMDS; 2) 1,2,4-trichlorobenzene
C14H18O4 H H
CO(OMe)2 reflux
TMS
98% 3) MeOH, reflux

2
PPh3, DEAD O
OH O
HO2C CO2Me H2, 20% Pd(OH)2/C H

N OH
MeOH, 59% N
THF, 70%
O
O

3
>300 °C, 10 s
+
10% 12%

∆, 83%
4 Br

Me O
NaOH, K2CO3
Cl
NaN3 NBu4+HSO4-
Me
O
t-BuOH toluene toluene
O
reflux 80 °C 160 °C N
81% 91% 75% Boc

5
KH (2 eq)
18-crown-6 (2 eq)

THF, rt
OH OH 84%
O

1) CDCl3, 65 °C, 80%

OH
2) KH (2 eq)
OH 18-crown-6 (2 eq)
THF, rt, 90%
 Fukuyama Group - Group Meeting Problems
11/28/2001

1 1) S CO2Me
Cl
OTs CO2Me
79%

N CO2t-Bu 2) m-CPBA (3.0 eq), 92% N CO2t-Bu

Boc 3) MeOK, 75% Boc
4) SmI2 (3.3 eq), MeOH, 80%

2 Cl
N
O
AgBF4, 1,2-dichloroethane, 0 °C;
RCONH2 RCOOH
0.01 N HCl, dioxane, H2O, rt;
Me2NH, i-PrOH, rt
RCONH2 = cobyrinic acid abcdeg hexamethylester f amide

3
O cat. Rh2(OAc)4 Me
S S Me
Me S O
Me (1.5 eq)
N2
CH2Cl2 Me Me
Me rt, 20 min O

4 R1 = H
OTBS

R2 = Ph or t-Bu R2
OTBS heat;
SiO2 OH
xs SeO2
R2
CDCl3
A OTBS
OH

R1 R1 = Ph or t-Bu
R2 = H OH

R1
OH

5
OEt MeO2C
1) LDA, THF H2C PPh3 dil. HCl
O
2) Cl
CH2Cl2, rt
O
CO2Me
 Fukuyama Group - Group Meeting Problems
12/05/2001

1
Dess-Martin Periodinane; NaOH

CH2Cl2, rt
R1 R1
N OH O
R2 R2
IBX

DMSO - THF, rt

2 PPh3
OH O
DMAD CO2Me

O O dioxane O CO2Me
10 °C to reflux

84%

3 Ph
iodobenzene
Pd(OAc)2 (5 mol%)

NaOAc, LiCl
DMF, 100 °C
60%

4
Ph H TMSCH=C=O (2.2 eq) N O
N
O Ph toluene Ph O
80 °C TMS
4 hr O

79%

5
1) BrCH2COCl, CH2Cl2, rt; O
S Et3N, CH2Cl2, reflux S
N
N NH N
2) NaIO4
MeOH/dioxane/H2O, rt
3) Ac2O, p-TsOH H
toluene, reflux
 Fukuyama Group - Group Meeting Problems
12/12/2001

1
1) NaH, benzene
O
OAc 80 °C, 30h
CO2Me O O O O
+ Ph 2) KOH, MeOH
rt, 3h
(1.0 eq) (2.5 eq) 3) TFAA, CH2Cl2
rt, 1.5h Ph Ph

2
t
Bu cat. NaH, Et2O, rt Xylene, reflux Ph
Ph + N CN
But N O
OH
63%

3
O O OH
Til4 (3.0 eq)
H + OHC Ar
EtO EtO Ar
EtCN
NTs NHTs
–78 to –20 °C
Ar = PMP 87%

4 N 1) NBS, CH2Cl2, TFA N

2) AgBF4
H H
N 3) H2O/THF N
H R COOMe H R COOMe
N

R= OH
MeO N OAc
Me COOMe

5
N OBn sunlamp
(Me3Si)3SiH N
BnO
hexane
H H
2 hr, 70%
 Fukuyama Group - Group Meeting Problems
12/19/2001

1
Cl 1) CH2Cl2 CO2Me
rt, 50h
CO2Me N
N
O 2) DMSO
O
100 °C, 2h

52% (2 steps)

2
1) 2.5 mol% Ti(OiPr)4
BzO 5 mol% BINOL O
O Et2O, 0°C, 1 h OBz
2) 10mol% p-TsOH
CH2Cl2, rt, 20 min
racemic 93%ee
78%

3 O
MeO2C MeO2C
Me CO Me NH CO2Me
2 1) PhN2BF4
NO2
aq. pyridine

2) NaBH4, MeOH
MeO N CO2Me 3) H2, Pd-C, HCl MeO N CO2Me
OMe OMe

4
O
O Bn
N
O
CH2OH O 1. MnO2, 96%

NH2 toluene, 65 °C 2. BnNHCH2CO2H N

56% toluene, reflux
68% O

5
Me
Me 1) phenylalanine NHtBu
t-BuNC, MeOH
CO2Me N O
O
2) toluene, reflux
TMSO
MeO2C
Ph
 Fukuyama Group - Group Meeting Problems
01/09/2002

1 Li H
Me 0.1 eq PhSH
O 0.1 eq PhSNa Me
MeO
TMSO C16H20O2
THF THF O O
H –78 °C; reflux
TMSCl (1.5 eq); 12 hr H
25 °C; HCl aq

2 MeN
O
O 1) MeAlCl2, CHCl3
O lutidine 2) NaBH4, MeOH, 63% (2 steps) NMe
MeO
MeO Cl 3) MsCl, Et3N, 94%
toluene
68% 4) t-BuOK, THF, reflux, 86% O

3 CrCl2 (8 eq)
TMSCl (6 eq)
O H2O (1 eq) O
R1 R2
R1CHO +
R2 THF
25 °C, 24 h

4
Ph OEt
OEt
N benzene
N Ph
reflux
H
67%

5
O 1) Me3SiOK
1) Boc2O, DMAP toluene, 70 °C;
NHBoc
HN Et3N, CH2Cl2 aq NH4Cl
Ar
Ar-C7H8NO
Ar
2) TBAF, THF-H2O 2) Pb(OAc)4
TESO O
3) DMSO, H2O, 130 °C t-BuOH, 50 °C
CO2Me
Cl
Ar = N
 Fukuyama Group - Group Meeting Problems
01/16/2002

1
PhSH 1) Li/NH3
O O aq HCHO THF, t-BuOH; O O
Et3N TMSCl, Et3N Me4NBH(OAc)3
Me MeCN-AcOH H Me
EtOH 2) Sc(OTf)3
O aq HCHO –40 °C HO
THF Me
OH

2
SmI2 (0.1 eq)
Ph OH H Ph OH
Ph (4.0 eq)
Ph O
Ph
O PhMe, 80 °C, 4 hr O
95%
Ph
O

3
DNs
NH2 O 1) cyclopentadiene, NaIO4, MeOH, H2O N
2) DNsCl, pyridine, CH2Cl2
NHOH
3) Pd(PPh3)4, THF, ∆ N
OH
O

4
MeOTf
OHC 1) MS 4Å 2,6-di-t-Bu-pyridine
CH2Cl2 CH2Cl2, 0 °C; OHC
+ n-Bu A O
2) Oxone®, NaHCO3 aq NaHCO3 n-Bu
MeCN-H2O 55%, >98% ee
Ph NH2 54%

Cr(CO)5 Ph
benzene
N
reflux O N
Ph
 Fukuyama Group - Group Meeting Problems
01/23/2002

O
1 CO2Me O CO Me
2
Rh2(OAc)4 (1 mol%) O
N2
O CH2Cl2
O reflux, 54% O

2
NO2 hν NO
ROH +
OR
CHO

OAc
OAc
3
Hg(OTf)2 1.2 eq H
tetramethylurea O

HO CH3CN
ArCO2 r.t., 5.5 h;
NaCl HgCl
Ar = p-nitrophenyl
22%

4
TMS DMAD (2.0 eq)
Ph N A
TMS Et2O
–78 °C to rt
16 hr C26H35NO8Si2
79%
TMS
TMS O OMe
n-Bu N (1.0 eq) N
TMS TMS
CO2Me
n-Bu Ph
Et2O
–78 °C to rt MeO2C
TMS
24 hr MeO N
33% O
TMS
5
Ph
1) benzene, 80 °C
Ph CO2Me
N O
2) PhCHO, DABCO (1.5 eq)
N3
Ph CO2Me
 Fukuyama Group - Group Meeting Problems
01/30/2002

1 SiMe3
AlCl3 (2.0 eq)
N
CH2Cl2 OH
NO2 –10 to 0 °C
O 84% O

OH
2
POCl3, 50 °C MeO
NMe N
MeO CHO 86% Me
OMe Cl
O

3
O O
Pd(dba)2, dppp
CO (6 atm)
DMF
N
NO2 H

74%

4 CN
CN
NC
i-PrNH2, hυ

MeO NH3, CH3CN-H2O NHi-Pr

MeO

5 O
OTIPS Me 1) ClTi(Oi-Pr)3, c-C5H9MgCl
THF, rt, 90% H OH
N
PMP H
2) SiO2, CF3CH2OH, rt; stereoisomers
O
P(OEt)3, rt, 68% H
TIPSO
PMP = p-C6H4OMe
 Fukuyama Group - Group Meeting Problems
02/13/2002

1 O
Me PhSH PhSCl, Et3N; Me SPh
C11H12O2S
O2 H2O, 75%
O
major product

2 NO2
(EtO)2P NO2
Ot-Bu Ot-Bu H
1) mCPBA O

2) Al2O3 NaOMe, DMF, 0 °C

74%

3
Me MgBr
O OH
–70 °C;
Cl LAH, 10 °C

THF

4
OEt 1) Me2NH
ether
(OC)5W
Ph OEt
2) pyridine
PhC CCO2Et EtO2C NMe2
toluene
60 °C, 2 h

5 OH
OPiv 1) hv
acetone, rt

2) aq NaOH, EtOH O
O OPiv 3) Li, NH3
H
 Fukuyama Group - Group Meeting Problems
02/20/2002

1
PPh3CH3+I– (2 eq) H
t-BuOK (2 eq) (CH2O)n
HO
Cl
O sulfolane
H toluene
reflux 100 °C
84% 82%

2
1) n-BuLi (2.0 eq), TMEDA;
TMSCl, THF, 73% Ph
Ph SH Ph
2) O benzene, 180 °C OSiMe
93%
Ph Cl , Et3N
Et2O, 95%

3
Me Me
EtO EtO
1) MeOTf 3) MeOTf, CH2Cl2
CHO 4) TBAF, THF N N
N 2) TMSCH2NH2
45 °C H
CH2Cl2, 0 °C Me Me
Me
77% (2 steps) 70% (2 steps)

4
1) CH3C(OEt)3
O OH
O OH cat. prpionic acid
reflux OBn
OBn N
N Ph
Ph 2) NBS, DME-H2O CO2Et
Boc
3) EtONa, EtOH CO2Et
4) LiHMDS, THF, –50 °C

5
O 1) n-BuLi (2 eq), THF O
–78 °C to 25 °C
R n-Bu
O 2) Me(MeO)C=CH2, TsOH
MgSO4, CH2Cl2 O R
3) SnCl4, CH2Cl2
–78 °C to 25 °C
 Fukuyama Group - Group Meeting Problems
02/27/2002

1 1) HOBr
2) LTA, I2, CaCO3 HO
HO
hυ, cyclohexane Tl(NO3)3•3H2O

3) Zn, AcOH-H2O dioxane

AcO rt AcO
AcO

R
HO
2
H
HO Swern oxidn
–78 to 0 °C;
NH3 (gas)
0 °C to rt; HN R

NH4OAc
AcOH;
rt to 70 °C
R = CH2CH2CH2OBn 82-95% overall yield

3
CO2Me MeO2C
PPh2Cl, Et3N
CH2Cl2, –78 to 0 °C;

xs.1,4-cyclohexadiene Me
PhH, 40 °C, 2 hr
PPh2
OH O
68%

4
1. Me3MgLi (1.0 eq) 1. n-BuLi, THF, 0 °C;
PhMe2Si SiMe2Ph THF, –78 °C n-C8H17I, rt C5H11 C8H17
A
Br Br 2. DBU 2. HBF4•OEt2, CHCl3, reflux; O
DMF, 90 °C TBAF, KHCO3, H2O2 aq 68% from A
THF-MeOH

5
Ph3P Ph xs. NO2, CH2Cl2 O2N NO2

O Ph rt
NC
 Fukuyama Group - Group Meeting Problems
03/06/2002

1
O TBSOTf (2.1 eq) O
collidine (4.2 eq)
CH3 CH3
CH3(CH2)14 N CH3(CH2)14 N
CH2Cl2
OCH3 rt, 3 hr OTBS
61%

2 HCOOH
O paraformaldehyde
CN
NH2
CH3CN
reflux, 12 hr
85%

3 Me [(COD)RhCl]2
O
OEt N
(OC)5W O Ph H
Tungsten-carbene N Ph
complex Ph
pentane, 20 °C THF-EtOH (5:1) Me
Ph 93% 20 °C, 69%
OEt

4
MeO 1) m-CPBA (1.1 eq)
CH2Cl2, rt, 3 hr CHO
N
H 82% CO2Me
N
H
2) NaOH, MeOH HO
N
N rt, 5 min, 71%
MeO2C Cl 3) TFA, CH2Cl2
rt, 15 hr, 52%

1) Li Cl
O
S
2) HgCl2, H2O
 Fukuyama Group - Group Meeting Problems
03/20/2002

1 Cp2TiCl2; OTIPS
MeMgBr, 1) BnNH2, Pd2(dba)3, P(o-tolyl) 3
OTIPS ; NaOt-Bu

MgBr Br2 (2 eq) 2) Pd-C, HCO2NH4, MeOH N

reflux H
Me Me

t-Bu
N 1) NaBH4, MeOH
O
0 °C
2 O
Cu
N 2) NaH, BnBr, DMF
Me t-Bu
Pentacyclic 0-23 °C Me
compound
COCN2CO2t-Bu toluene 3) DIBAL, CH2Cl2
O reflux –10 °C OBn
O
4) Tf2O, 2,6-lutidine
( racemic ) CH2Cl2, –78 °C

3 O
NBS, TMSN3 heat in toluene O Ph
COPh N
MeO2C
PPh3 MeO2C Br

O
4 CO2Et Ti(Oi-Pr)4 1) FeCl3
2 i-PrMgCl 2) AcONa
C12H24O2Si
TBSO Et2O TBSO

1) 30% aq HCl
5 N Cl cat. Cu(bpy)Cl reflux, 18 h
"Olefin" N
CO2Me ClCH2CH2Cl 2) pH 13
reflux, 48 h

66%
 Fukuyama Group - Group Meeting Problems
04/03/2002

1 O Cl O O N

O O N O
TFA
+
O
AcO H OAc H
OH AcO OAc
AcO H
AcO

2 1) A, Et3N
dioxane, 25 °C
MeO2C N Ph
HN NH2 2 days, 84%
NH
Ph 2) dimethyl fumarate MeO2C
170 °C, 8 h, 84% O
1) KOH, MeOH
Cl ethylene, Na2CO3
Cl 85 °C
A
Cl CCl4, 170 °C +
Cl 2) H3O , CH2Cl2

3 O OH
Br O

O 1) DBU 3) NBS, H2O O

O O
2) O 4) KOt-Bu (3 eq) O OH
O

4 H SPh
1) NaH MeO CO2H
2) m-CPBA
O
O 3) KOMe, MeOH
OH

OMs
(racemic)

5
SiMe3 O
O
1) 300 °C, neat

2) Pd(OAc)2, CH3CN
 Fukuyama Group - Group Meeting Problems
04/10/2002

1 MeO
O
MeO

SEt 1) CSA, benzene, reflux N O

MeO N 2) NaI, acetone MeO
H
CO2Me
3) NaH, THF, reflux SEt
H
MsO O

2 O Me OAc
OAc Me
1) NaBH4, MeOH
OAc
Me 2) p-TsOH, benzene
OAc

3
HO CO2Me O O
O O NaHMDS;
CO2Me P(OEt)2
DMAD O
P(OEt)2 +
toluene P(OEt)2 CO2Me
O

37% 29%

4
S S
AlEt2Cl SH
PhO S
CH2Cl2, rt N
NPMP 67% PMP

5 O
*Ti/graphite, DME Ph
Cl Cl
Ph
reflux, 1 h COOEt
NMe N
O 94% Me
O
OEt * Ti/graphite was prepared from
K + 8C(graphite) + TiCl3
 Fukuyama Group - Group Meeting Problems
04/17/2002

1 H
N NH2
N Bu3SnH
SeO2 AIBN
O A
AcOH benzene
∆ 80 °C
A contains Se atom

1) t-BuOK
2 O EtCOCl CO2CH3
CO2CH3
–78 °C (xs) H2SiF6
HOOC
2) NaHMDS ∆
TBSCl
–110 °C

3 H
N
H
N
NCS, CCl4;
+ A
MeOH MeO
rt, 40 min.

AgNO3
A
MeOH N
5 °C, 20 min. OMe

4 15 eq CO2t-Bu
0.67 eq PhSSPh
cat. AIBN CO2t-Bu
CO2t-Bu
benzene t-BuO2C
reflux

53%

5 1) 10% KOH
O Ph MeOH-H2O, reflux
O
2) (MeO)3P, EtOH, reflux
S
Ph Ph
H N 3) MeSLi, DMF, 0 °C
4) (HCHO)n, CSA, Na2SO4 N
CO2Me MeCN, reflux
 Fukuyama Group - Group Meeting Problems
05/01/2002

1 1) LHMDS (2.2 eq), THF; I2 OH

NHBoc 2) Cu(OTf)2, CH2Cl2
CO2H
CO2Me Ph
Ph 3) LiOH, H2O NH2

O
2 Ph O
Ar Ph Ph
Ph
(2.0 eq) Ph
Ar
N N N N
xylene
140 °C, 20 min Ph
H
Ar = p-MeOC6H4- 57 %

3
O
H O SO2Me
t-BuOK, t-BuOH; H+

30 %
O
O O O
SO2Me Me

4
1) i-amyl nitrite*, HCl
3) hν, Pyrex CH(OMe)2
Et2O, 5-15 °C, 1 hr
O C9H4N4O
2) NH3*, NaOCl*, NaOH MeOH, 3 hr CH2CO2Me
H2O, 10-20 °C, 1.5 hr 69%
47% (2 steps)
*: 理論上2 eq.
Me
5 N
N OH
N
H n-BuLi, –78 °C;
Me CHO
TsOH, PhH, reflux O
Me CHO
N
–78 °C to rt
Me
 Fukuyama Group - Group Meeting Problems
05/08/2002

1
H
1) HCHO, Me2CHNO2 cat. BTAC , cat. NaCN , acetone (2 eq) N
NH2
2) Raney-Ni, H2 CHCl3 (1.5 eq), CH2Cl2 , 50% NaOH
Ph N O
0-5 °C
Ph
BTAC: benzyltriethylammonium chloride

2
(Me3Si)3SiH
AIBN, PhH
(Me3Si)3Si
O ∆, 4 h O
CH2 89%

3
1) EtOH, reflux, 66% EtOOC H
OH 2) PhCOCl, Pyr, 81%
PhNH2 Ph
Ph CN N Ph
3) HBF4, AcOH, 70% H
O
4) CH2=CHCOOEt, DMF, 65 °C
75%

4
I C3H7
Ph
SmI2 C3H7
O Ph + C3H7
benzene-HMPA OH
OH
68% 2:1

5
O O

HN O 2eq Pb(OAc)4 N
+
HN CH2Cl2 N
CHO
O HO2C O
64%
 Fukuyama Group - Group Meeting Problems
05/15/2002

1 MeO OMe 1) OAc 3) PDC, CH2Cl2 CO2Me

Br Br toluene, reflux 4) heat, neat

2) K2CO3, MeOH 5) Bu3SnH, AIBN

Br Br benzene-THF OH

1) TfOH, benzene, 0 °C;

N3
2 NaOH aq (work up)
82 %
N
2) Pd/C, H2
Ar 94 % Ar

Ar = 3,4-(methylenedioxy)phenyl

3
MeO2C
CN piperidine, H2O CN

S CO2Me rt, overnight H2N S CO2Me

69%

4 1) LDA, THF, –78 °C 1) LDA, THF, –78 °C

2) HCl/Et2O; 2) HCl/Et2O;
Piv t-Bu
Boc ClCO2i-Bu, NMM ClCO2i-Bu, NMM Ph
N O
Ph O N-Bz-Gly N-Cbz-Gly Ph O
N O
N 3) TsOH, PhMe, ∆ 3) TsOH, PhMe, ∆ N N
NHCbz
4) Boc2O, DMAP

NMM = N-methylmorpholine

5
O
TMSCHN2, n-BuLi
DME, hexane;
O O
silica gel HO O

64%
 Fukuyama Group - Group Meeting Problems
05/22/2002

1
1) PhH, rt
overnight, 73% Me
N3 R H
2) n-PrOH, reflux R
2 h, 70% O
H N
3) N-methylpiperazine N N N
Me O O
O reflux, 4 h, 65% O N
Me
R=2,4-chlorophenyl-

2
1) –80 °C to rt MeO2C
O OLi 2) NaHMDS;
Davis' oxaziridine TBSO
SiMe2t-Bu +
3) LTA
t-Bu MeOH-PhH
t-Bu CHO

3
O H H H
O 1) MeMgBr O
O H H p-TsOH 2) POCl3, Pyr

∆ O
O hν 3) Pd(PPh3)4
O PPh3 O O
OMe

4
SiMe3 I I
I(OAc)2
Me Me BF3·Et2O Me Me Me Me
+

30% 47%

5
1) OEt , hν, 0 °C, 55%
EtO2C O 2) DBU, benzene, reflux, 70% EtO CO2Et

Ph N O 3) DDQ, benzene, reflux, 65% Ph N CO2Me

H 4) NaOAc, MeOH, reflux, 80%
 Fukuyama Group - Group Meeting Problems
06/05/2002

1
CO (2 atm) O
H
O O [Rh(CO)2Cl]2 (5 mol %) O

dioxane
60 °C, 24 h; OH
O
workup H3O+
97%

2
Br 1) n-BuLi, H O
Br THF, –100 °C; 2) H2O2, NaOH

H O 3) Co2(CO)8
Ph B DME H
H Ph
O rt to reflux
–100 °C to reflux

3 N
hν
NH
NH3, MeOH; N
NH2 CO2
CO2H N
H 78%

4
3) Al(Oi-Pr)3
Me OTBS 1) H2NOH•HCl, Py N-methyl-4-piperidone Me OH
O reflux toluene, reflux, Dean-Stark
Me

2) LiAlH4, THF 4) aq. HF, MeCN

reflux 5) NaNO2, H2O, AcOH
HO O

5
1) LDA (2 eq);
3) MeLi
I
CO2H
2) (COCl)2; 4) Mn(OAc)3•H2O
Et3N, toluene Cu(OAc)2
reflux O
EtOH, rt
 Fukuyama Group - Group Meeting Problems
06/12/2002

1
O H3CO2C
Rh2(OAc)4, CO2CH3
COCH2OH
CH3
N CH2Cl2, rt, 1.5 h;
COCHN2 N CH3
silica gel
84%

2 O O
NaHMDS, THF;
+ NEt2
OMe NC NEt2
aq. NaOCl
N N O

71%

3 LiCHBr2, THF;
O n-BuLi (2 eq),–78 to 25 °C;
A
O OH
quenched with i-Pr3SiCl
hυ (vycor) OSii-Pr3
A N2
O ClCH2CH2Cl O OSii-Pr3
O rt 3.5 h ; 2 h

4
CO2Me
N2 Cu(II), PhH, reflux MeOH, 60 °C
OMe O
N 95% N
86%
O O

Cu(II) ; Copper trifluoroacetylacetonate

MeO
HS Ts NaI, NaOH CsF, MeCN
N Me3Si Cl
MeS EtOH, reflux 4-Methoxybenzaldehyde
71% 85% S
 Fukuyama Group - Group Meeting Problems
06/19/2002

O
1 4) NBS
1) PhNCO, Et3N 2) HCl aq DMF O
MeO2C NO2 hexane, 50 °C; THF, rt 0°C;
O
O 3) NH2OH·HCl Et3N;
A N
Py, rt A, rt
O O
MeO2C N
96 % (2 steps) 70-90 %

2
Cp2ZrCl2(1.05 eq), PhHN
n-BuLi(2.1 eq), THF, –778 °C;
H
added SM, –78 to –20 °C; Me
PhNC, 70 °C; MeOH H
21% overall racemic

3
1) DBU, 80%
2) TsOH, MeOH
refux, quant. CO2Me
O + CN CO2Me O NH
3) triphosgene, Et3N
O O
THF, –50 °C, 87%
O

4
1) O N
O
Et3N; H3O+, 82%
2) AcCl, py, 0°C, 80%
COCl
3) hν (Pyrex), 78%
4) 4% KOH in dioxane-H2O (1:1) OH
100 °C, 72%

5
1) O O , 120-130 °C MeO O
88%
O
N
O 2) hν, MeOH, 59%
OH
 Fukuyama Group - Group Meeting Problems
07/03/2002

1 OTBS
1) NH4OH, 62% CHO
2) PhCOCH2Br, 2,6-lutidine
toluene, ∆, 26%
O O O
3) OHC CH2OTBS O O
CO2Me tetralin, 205-208 °C, 52%

2
1) Br2, MeOH-ether
–35 °C, 30 min, 73%
CO2Bu CO2Bu
O
OH 2) 2% H2SO4
O
rt, 90 min, 30%

3
1) LDA (1.1 eq), THF, 0 °C;
O TBSCl (1.5 eq), –78 °C, 73% TMS
N
N N 2) LDA (3.3 eq), THF, 0 °C;
H N TMS
TMSCl (3.5 eq), 65%
3) 200 °C, 82%

4
LDA; MeI
O Me NEt2
Et2NH THF MeMgI, Et2O
OH
Cl Me
rt –78 °C to rt reflux
Ph 85% 68% 95% Ph

5
PPh3 (2 eq)
CCl4 (2 eq) 1) RCOCl
H Et3N (2 eq) CH2Cl2 O
N N2
H2N CHO R
CH2Cl2 2) TsCl (20 mol%)
reflux Et3N, CH2Cl2
 Fukuyama Group - Group Meeting Problems
07/17/2002

1) NaOEt, MeI
O O 2) conc. HCl; NaOH
1
O Br
3) MeLi
4) conc. HBr

Et3N
O
2 HS SH Me

N3 MeOH
N

3 Mo(CO)5
2)
OH Me O- Me N+
4
1) Tf2O, pyridine CH2Cl2, 0 °C H

CH2Cl2, 0 °C 3) benzene, 65 °C O
Me
CO2Et CO2Et

4
Br O
1) t-BuOK
O THF, 0 °C 3) P(OMe)3 N
O
O N 2) Lawesson's rgt reflux Et S
O OH O THF, rt
Et O

5
O O
1)

Li+ S
N CH2- 2) Lawesson's rgt N
3) BrCH2COPh Ph
Et3N
 Fukuyama Group - Group Meeting Problems
07/31/2002

1
O O
1) mCPBA (1 eq), CH2Cl2, rt, 86%
NH2 NH2
2) AcCl, CH2Cl2, 40 °C, 71%
PhS SnBu3 AcO SPh

2 O
OH TFAA, Py
CF3
Ph
Ph CO2H PhH, 80 °C
OH

3 O N2 OH
O 1) Rh2(OAc)4, solvent O
CO2Et HO
HO COOH
OAc 2) TFA, EtOH
O quant. (2 steps) OH
O

4
1) BSA (3.0 eq) 3) LHMDS, AcCl
ethyl vinyl ether CO2Me
THF, –78 °C
MeO2C
NO2
2) MeOH/CH2Cl2 4) butyl vinyl ether BuO N
toluene, reflux Ac

BSA = N,O-Bis(trimethylsilyl)acetamide

5
O3, NaHCO3
O t-BuOK MeOH-CH2Cl2 O
t-BuOH-THF –770 °C;
CO2Me

Br 70% Ac2O, Et3N, DMAP

benzene, reflux
 Fukuyama Group - Group Meeting Problems
08/21/2002

S
1 O
S
Sn(tpp)(ClO4)2 (3 mol%) O
S +
CDCl3, 20 °C, 2 hr S S
Ar Ar S 46%
Ar Ar
=
Ar Ar

2 O
Cr(CO)5

MeO H
+
dioxane H
CHO
100 °C
OH

3 OMEM OH
hν
OMEM H2SO4 OMEM
O +
CH3CN

O hν
H2SO4

CH3CN

4
Me
1) CHBr3 (>2 eq), t-BuOK

2) MeLi (2 eq), –78 °C Me

3) H2, Pd/C Me

1)
n-Bu
5 EtO2C NH
CO2Et
OMe CSA, CH2Cl2, 0 °C, 15 h H

N 2) CH3CHO, Al2O3, CH2Cl2

Bn N
rt, 15 h; Bn
NaBH4, MeOH, rt, 1 h;
aq. HCl 38%
 Fukuyama Group - Group Meeting Problems
09/04/2002

1 1) CH2N2 (gas), Et2O, –78 °C, 87% HO Ph COPh

S
2) PhOC COPh , CH2Cl2, reflux, 63%

O 3) TFA, CH2Cl2, 70% O S

2 Me + BF4
- 1) EtSO2Cl, Et3N (2 eq)
NH THF, 0 °C, 70%

2) n-BuLi (1 eq), THF, –78 °C; N Me

MoO5·HMPA-LDA in THF (1.1 eq), –78 °C;
Me
rt ; water, 45 °C, 81%

3 O O
2 eq PhP(SiMe3)2 MeOH
Cl OMe
C26H38O2P2Si2
Cl CH3CN, –15 °C reflux, 24 h OMe

O O

4
CN O O
[Rh(OAc)2]2 NC N O
CO2Et
+ H3C CH3
S N 70 °C, 1 h
N2 140 °C, 1 hr
S CO2Et
O

5 1) NaNO2, aq AcOH, 10 °C
2) PPh3, Et2O
BocNHNH2 Reagent A
3) Cl3CCHO, toluene, reflux
4) Oxone, K2CO3, H2O-CHCl3, 0 °C

OH

MeO 1) A, CH2Cl2 MeO

OH
2) TFA OH
N O
3) NIS (2.5 eq)
HN N I
 Fukuyama Group - Group Meeting Problems
09/18/2002

1
H 1) NaIO4
SiMe2Ph 2) heat, PhH
Si H H
SiMe2Ph
3) H2O2, KF HO H
PhS KHCO3

2
O P(OEt)3 (1 eq.)
A
Cl Cl
40 to 100 °C, 1 hr 99%

LDA, THF, –78 to 0 °C;

A, Pd(PPh3)4, rt, 3 hr;
O
O NaOH, EtOH-H2O
reflux, 24 hr
79%
3

3) Lawesson's
H3N CO2 1) LAH reagent
A
2) HCO2Et

HCl (g)
OBn hν MeOH; BnO Me
(OC)5Cr
Me A I2 MeO2C CHO
76% acetone/H2O

4
1) Ca(OCl)2, CO2, H2O
CH2Cl2, 65%
CHO
O
2) cat. Pd(OAc)2, Ph3P, AcONa
150 °C, 66% (E:Z=59:41)

5
MeO Ph
N PhMgBr (2.2 eq)
Br N N
Ph THF
Br –42 °C to rt Ph Ph
 Fukuyama Group - Group Meeting Problems
09/25/2002

1
NC H
1) CH2N2 (ex.), CH2Cl2
NC
Ts Se 2) mCPBA, CH2Cl2, – 10 °C Ts OH
Cl

2
Ph aq. glutaradehyde (2.5eq) O
OH pH3.5 , TolSO2Na ; ZnBr2 Ph N
NH2 R
O

R : TolSO2

3 1) N2CHCO2Et, CuSO4, PhH, 65% O

OTMS 2) PPh3 BF4 , KF, 18-crown-6, MeCN, 82 °C, 95%

SPh
3) NaOH / H2O, MeOH, THF, 60 °C
t-BuO2C 4) ClCO2Et, Et3N, THF; NaBH4, THF / H2O
5) TFA, CHCl3, 43% (3 steps) O
O

4
t-BuOOH OHC O
OH H
cat. VO(acac)2
O MEMO
OMEM OH
CH2Cl2 toluene
0 °C 110 °C H
48 h
56% (2 steps)

5
Ph 1) BF3•OEt2 (3 eq), PhSH (5 eq)
OCOi-Bu CH2Cl2, rt, 1.5 h, 57% i-BuCOO n-Bu
N
Ph OCH2OCH3
O 2) W-lump, O2, rose bengal H3C O
CH2Cl2, 3h, 35% O
n-Bu CH3
 Fukuyama Group - Group Meeting Problems
11/06/2002

1
DMF (~2.0 eq) OH
Br Bu2Mg (0.52 eq) n-BuLi (1.1 eq) –20 °C;
O
COOH THF –20 °C; 2N HCl
–20 °C; O

2 1) hν
CHCl3, rt, 8 h
2) PPh3 CO2Me
CHO toluene, reflux, 3 h
+ CO2Me
N
3) methyl propiolate
N3 toluene N
140 °C, 12 h

3
N N
1) HCl, MeOH 3) NaBH4, CeCl3
reflux, 44% MeOH, 88%
C23H26N2O5
N O 2) ClCO2Me, Na2CO3 4) MsCl, Et3N, DMAP N
H CH2Cl2, rt, 84% CH2Cl2, 91% MeO2C
CO2Me CO2Me
5) Et3N, EtOH, H2O
60 °C, 83%

1) MOMCl, i-Pr2NEt
4 OH A
2) cat. t-BuOK
3) n-BuLi
HO
Li-morpholineamide (2 eq) O
Br Br –78 °C, 1 h; A, –78 °C, 2.5 h;
Br
Br isobutyraldehyde HCl/EtOH, 0 °C
reflux, 1 h THF, 75%
THF, 71%
5

1) I2 (1.5 eq)
OMe collidine (1.5 eq)
CH2Cl2, rt 1) I2, EtOH-H2O
84% (95:5) 78% NHBoc
Amino acid
N derivative CO2Me
2) NaN3, DMF 2) Zn, THF
3) SnCl2, H2O; 3) CH2N2
O OMe Boc2O, Na2CO3 87% (2 steps)
83% (2 steps)
 Fukuyama Group - Group Meeting Problems
11/13/2002

1
Ph

N Rh2(OAc)4 (1 mol%) O
N
O Ph dichloroethane H Ph
130 °C

note: stereoselective

2
DMF, MeTi(Oi-Pr)3 H NMe2
c-HexMgBr
C11H19N
THF, rt, 14 h decaline, 220 °C, 1 h
63% 90%

3
1) NaNHNH2 3) triisopropylbenzene
ether-THF, 0 °C, 2 h reflux, 5 h, 80%
N N
N
2) HO O O OH
CN
HO O O OH
MgSO4, EtOH, rt, 12 h
(68% in 2 steps)

4 NO2
O
O O2N S NH2
O
CN
Cl
Et3N, THF MeO
MeO reflux, 24 hr
76%

5
MeO O MeLi (1 eq)
THF, –100 °C;
A
MeO O TFAA, –78 °C;
PhNH2, –15 °C
Me
Me 1) n-BuLi, THF, –78 °C;
O O
O A, –78 °C; R
R oxalic acid, H2O, rt Me
Br Me
Me
2) toluene, 110 °C; MeO OTIPS
OTIPS air, rt
O
R= OTBS
Me
 Fukuyama Group - Group Meeting Problems
11/20/2002

1
OMe
OMe
Hg(OTf)2, THF
rt, 30 min; H
N
N3 NaBH4, MeOH H
0 °C to rt, 14 h

47% (α:β = 2:1)

1) , hν 3) NOClgas 4) TsOH
O
quant. pyridine, –20 °C; benzene

2) n-BuLi hν, pentane reflux O

O 71% 85% in 2 steps

3
3) MCPBA, CH2Cl2 CO2Me
O 1) aq. NaOH –78 °C, 30 min H
PhH, reflux, 3 hr; 66% (2 steps)
H
O N
H CH2N2, Et2O 4) hν
65-70% MeCN, quartz tube H
O
2) tryptamine, MS4A 6 hr, 60% N
Et2O, reflux, 24 hr H

4
O

O O
N3 N3
BF3•OEt2 SbCl5
CO2Me "tetrahydrofuran"
HO CO2Me
CH2Cl2 CH2Cl2
SiMe2Ph Me
–50 °C –50 °C

5
Bu
1) NH2OH•HCl
Py-EtOH toluene, reflux N
Bu
O
O 2) NaBH3CN
MeOH, pH 3-4
 Fukuyama Group - Group Meeting Problems
11/27/2002

1 NaH; cat. CuCl

acryloyl chloride
HN A
toluene, rt, 23 h
S 56%
O2
1) A, PhNCO 3) LAH, ether
Et3N, benzene rt, 20 h, 97%
rt, 48 h, 70% 4) NH2OSO3H (2 eq) O
O O
H NO2 2) xs MeMgBr, THF aq NaOH, CH2Cl2 O
–78 °C, 45 min; 0 °C, 75 min, 54%
rt, 90 min, 72% 5) cat. TsOH, benzene
60 °C, 48 h, 61%
2
Ph
NO2 N (4 eq) ,PhH; CH3COCl
H NC CN
Py H N
O PhCHO (1 eq) hexane O N
O
(2 eq) 90% 90%

3
Me
OH
OMe 48% HBF4
O
MeNO2 OMe
O N2 91%

4
Hept
H Sit-BuMe2 NOBF4, CH3CN, –30 °C; N
· Br
Hept Me Br2, CCl4 O
Me
72%

5 OMe
1) cat. Ti(Oi-Pr)4
EtMgBr (2 eq) MeO Br
n-Bu3SnH H
O
CO2Me 95% TiCl4 cat. AIBN

2) TMSOTf CH2Cl2 benzene H

2,6-lutidine –40 °C reflux OMe
CH2Cl2, 88%
71% 95%
 Fukuyama Group - Group Meeting Problems
12/04/2002

1
OAc
SMe
OH
Me2S SMe
OMe BF4 reflux
N O bycyclic N
compound toluene
O
O

2 O
O Ph Ph2S2, AIBN
Ph
O Ph PhCl, hν, reflux
52%
Ph

3
CpW(CO)3
O O O
TfOH Tungsten-contained 1) (CO2H)2, 75%
ethyl ester O
OEt EtOH-CH2Cl2 2) NOBF4, LiCl
CH3CN, 47% H
OEt 65%

4
O O
HgCl2 LiPdCl3, CH3CN, 0 ºC to rt;
COOH A
K2CO3, reflux CHCl
23% 59%

5
Cl
R (CH2O)n, AlCl3 (0.5 eq)
R
R' CH2Cl2, rt, 2 h; H2O R'
O
62%
 Fukuyama Group - Group Meeting Problems
12/18/2002

1
1) TIPSOTf, i-Pr2NEt
O Et2O-Hex TMSCHN2 Sii-Pr3
N2 0 °C to rt CH2Cl2-Hex, rt;
A
2) hυ SiO2, rt O
benzene

1) MeO OMe
2 1) TFA OMe
Cr(CO)5 MeO OMe THF-H2O O
98% 85% NHt-Bu
MeO Tricyclic compound O
2) t-BuNC 2) MeOH
THF 100 °C MeO
85% 92%

NaCH2S(O)CH3 CHO
S
O2
NO2 THF-DMSO
rt

Bu
4 Cl
Pd(PPh3)4
N
(1 mol%)
N
Bu
THF, rt Cl

85%

5
1) NCS, Et2O
O O
2) cat CuCl, CuCl2 Me N
MeHN aq AcOH-THF

3) aq HCl, MeOH O
4) toluene, reflux
 Fukuyama Group - Group Meeting Problems
12/25/2002

1
MeO 1) Bu3SnTMS, CsF 2) PPA, 60 ºC MeO
N DMF, rt 40 h, 66%
H N
MeO MeO
OHC 8 h, 85%
I PPA=polyphosphic acid

2
O
NaN3 (ca. 5 eq) O
O
N
MeCN/H2O (3:1) O
Cl
rt, 5 min
97%

3
2) MeOTf
1) BuLi benzene, 0 °C Me
N ether, –20 °C; 96% Me
S
S SiMe3 Me
3) CsF
DMSO, rt; MeO CH2SMe
MeO CH2Br
aqNaOH, 68%
58%

4
N3 H H
H Bn2NH, AcOH Pd(OH)2/C, H2 N
HO O OH HO NH2
EtOH, 40 °C MeOH
HO OH HO OH

5
O O
(TMS)3SiH
Me
AIBN
H
N3 NH
 Fukuyama Group - Group Meeting Problems
01/08/2003

1
O O O
SOCl2 (ex.)
Ph NO2 Ph Ph
N N N
H rt, 52% H H
N N
O O

2
O O
O NHMe 80~110 °C, 5 h EtO2C
O NMe
Ph OEt 74% Ph
O O O

3
H H
N BrCN, Et2O, 0 °C; N
NH2 NHAc
AcCl, Et3N diphenyl ether
190 °C, 2.5 h N
55%
76%

4 SMe 1) I2, THF, 69%

2) Na2CO3
O NEt THF/dioxane/H2O, reflux, 71%

3) 0.5 N NaOH NHEt

EtOH/H2O, reflux, 64% OH
(racemic)

5 O

1) KOt-Bu, O2, P(OEt)3 H

HOt-Bu, DME, 79% O
N N
2) NaBH4, THF, 76%
H
N 3) NaIO4, 53%
N
PhO2S PhO2S
 Fukuyama Group - Group Meeting Problems
01/15/2003

1
OH
O 1) LDA, THF, –78 °C
O 2) CF3SO3Me, CH2Cl2, 0 °C to rt

3) t-BuOK, THF
O

2
OH (NH4)2SO3·H2O NH2
OH OH
NH3·H2O
200 °C, 5 d
91%

3 1) n-Bu3P, DMF, 0 °C
H
H
N
N O O
S S then O O

47% Br Br
N N 2) 1,2,2,6,6-pentamethyl-
H H N N
piperidine (cat) H H
toluene, reflux, 72%

Me O MeCO2Me
O t-BuNC, DMAD CO2Me
O O
CH2Cl2, rt, 24 h
O 94% O NHt-Bu

5
O CO2Et

SnCl2 (5 eq)
S
S S EtOH S
reflux, 2 h N
NO2 H
98%
 Fukuyama Group - Group Meeting Problems
01/22/2003

1
n-BuLi (1 eq), THF;
B(n-Bu)3 (1.1 eq); Ph
Ph BCl3 (1.1 eq);
OH
OMOM MeOH;
n-Bu
30% aq. H2O2-NaOH
89%

2
CO (2-3 bar), Pd(PPh3)4
K2CO3, n-Bu4NBr O
I
O

NHTs
CH3CN N
Ts
70-80 °C
61%

O
NH4Cl
3 CO2Me toluene
MeO2C N
rt, 1 hr;
+ OHC C6H13
O O
NH2 CN
N
O N C6H13
Ph
reflux, 1.5 hr

4
SO2Ph O
1) t-BuOLi, –60 °C
2) DDQ O
O + O
3) toluene, reflux
O O
O

O
5 OTIPS

1) PhI(CN)OTf 2) KF on Al2O3
SnBu3 CH2Cl2, –40 °C; (under air)
MeO MeO
LHMDS N
DME, –40 °C
MeO NHTs MeO
 Fukuyama Group - Group Meeting Problems
02/12/2003

1
18O
MeO2C hn MeO HO
H

O dioxane/H218O O

S 1) mCPBA, CHCl3 S
OPh 2) CHCl3, reflux
OPh
3) 20% aq. KOH O
N O N O
Me Me

3 OMe
Mo(CO)5
O THF, 67 ºC MeO2C
OMe + CO2Me O
2 hr, 71%
O
O

4 NO2
Cl

O
NaOH, O2N NO2 NO2
N
acetone, ~60% PhH, reflux
N 6 hr, 74%
OH
O2N NO2

5
O H
DBU, NIS Bu3SnH, AIBN O O
"tricyclic compound"
CH2Cl2, rt t-BuOH, reflux
OH 73% 50% H
 Fukuyama Group - Group Meeting Problems
02/19/2003

1
O Lawesson's rgt (1.1 eq) O
NO2 NH2
N toluene, 100 °C, 15 min N
H H
68% S

2
1) NH2, H2O, 81%
O
2) Tf2O (2 eq.), py Me
CH2Cl2, 83%
O
3) toluene, reflux N
SO2CF3
Me

3
DPPA Cy2BH, THF
DBU 0 ° C to rt, 12 h;
OH N
toluene MeOH H
N rt N
85%
90%

4
H Ph
H Ph
O r.t, CH2Cl2, 3 days
+ PPh3CHCO2Bn BnO2C H
O 95%
H COPh
H Ph

Me
5 N,N-diethylaniline
MeO
O O MeO
225 °C, 12 h O OH
MeO
MeO
MeO 40%

1) PIDA, MeOH Me
O
MeO
2) p-TsOH, MeOH
O PIDA = phenyliodonium diacetate
reflux, 1.5 h
MeO 49% (2 steps)
 Fukuyama Group - Group Meeting Problems
03/05/2003

1 1) n-BuLi (2 eq), TMEDA; HO

RCHO, THF, 62%
2) PPTS, toluene, 85%
OH O O
O 3) Pd/C, H2, EtOH, 90%
4) BF3•Et2O, THF, 85% O
O
R=
O

2
1) Rh(II) H
benzene, rt O
N2 10 min, 94%
O N O
Ph 2) xylene, 145 °C
O O 13 hr, 68% N
O Ph
[Rh(II) = Rh2(pfb)4]

3
Mo(CO)5

Bu OMe W
W
W W benzene
40 °C Bu
W = CO2Me
54%

4
Me OMe
(0.5 eq :
theoretical amount) O2N O O
N N
NO2 +
CHCl3 - MeNO2 O2N
rt, 10 min
2 : 3 mixture

5
1) n-BuLi, –78 °C
OH

Cl O
Cl 2) n-BuLi, 0 °C
 Fukuyama Group - Group Meeting Problems
03/12/2003

1
1) Lawessons' reagent
2) COCl2 (2 M in tol.), cat. DMF Ph
O O
0 °C,to rt, 1 h; evaporation; Cbz-L-Phe H
Cbz N
N CO2Me N N CO2Me
DABCO, THF, rt, 20 min; CH3CN H
Me filtration; rt, 19 h O Me
NaN3, 46%
83%

2
O
O 1) PhNMe2 O
180 °C, 6 h, 87%
Me
2) cat. Zr(acac)4, TBHP (2 eq)
CH2Cl2 Me
20 °C, 6 h, 71%

3
1) BrCH2CO2Ph
OH i-Pr2NEt, MeCN
OH TIPSO
2) TIPSOTf, Et3N OH
NHBn N
benzene Bn
3) LiAlH4

4
O
Me3Si
1) Br2, MeOH
CO2Me 2) AgNO3, MeOH CO2Me

3) TFAA, DMSO
CO2Me CO2Me

5
CO2Me
1) CH2Cl2, rt
CO2Me 5 days, 70%
+ N N
Cl 2) DMSO, 100 °C
O 3 hr, 73% O
 Fukuyama Group - Group Meeting Problems
04/09/2003

1 O O
1) LDA (3 eq), THF O
O –78 °C to reflux
2) toluene, 80 °C

3) EtAlCl2, CH2Cl2
0 °C to rt

2 NaH (2.4 eq),

O Me H
Me I
S (2.4 eq)
Me O

DMF, rt O
O O H
OH O
54%

R R
3
HO OAc OH OH R=

[CF3CO2ReO3·2MeCN]
TFAA PCC R R
O O
H OAc OH H
CH2Cl2-MeCN (9:1 v/v) CH2Cl2 HO OH
–40 °C, 1.5 hr, 84% 30 min, 47%

4 1) TsNCO, Et3N
O THF, rt, 94%
O
2) Br
OH N
Ts
Pd(OAc)2 (5 mol%)
P(o-tol)3 (11 mol%)
Na2CO3, n-Bu4NCl
CH3CN, 90 °C, 77%

5
1) benzene, rt
overnight, 93%
COCl H O
2) CH2N2, overnight
+ 34%
ClOC 3) benzene, 170 ºC
85% H
 Fukuyama Group - Group Meeting Problems
04/16/2003

1
O H CO2Et
O CO2Et FVP*
C13H19NO4 O
O N3 PhH, reflux 15 min N
overnight

44% FVP*: 520 °C, ca. 10-4 Torr

2 i-Pr
1) i-PrNH2
CCl4 xs. KCN N
C8H15Cl2N H2N CN
n-BuCHO
2) NCS (2 eq) DMSO
CCl4 120 °C Et
85% (2 steps)
71%

ONa
3
O Me NH2 O
OH NCS
OH N cat. pyridine Raney Ni, H2
O OEt , EtONa
H CHCl3 EtOH EtOH O Me

O OEt

4
O OR Me
H 1) H2O, dioxane, reflux;
Me N O
N recrystalization, 67% O
N O
O
N 2) HCl, EtOH, 98% N N NH2
O N
Me H H
Me
R = (–)-menthyl

5
1) Mg; 2) SOCl2

Cl O 3) Mg;
O2 OH
 Fukuyama Group - Group Meeting Problems
04/23/2003

1 NH
O
1) Me CCl3 4) n-BuLi
Me CO2Et cat. TfOH, 85% –78 °C, 75% Me

OH 2) DIBAL, 82% 5) H2, Raney-Ni, 95% Me

O
3) n-PrPPh3Br 6) KH, 18-crown-6
n-BuLi, 98% rt, 75%
(S)-ethyl lactate > 96% ee

2
a (exclusive)
H
O N3 PPh3, MS4A; O N
AcO AcO Ph
O O
AcO OAc Ph
AcO OAc
OAc S N OAc
CuCl2•2H2O;
H2O

3 1)
SeCN

NO2
n-Bu3P;
30% H2O2 aq. 84%
+
OH H H
2) hn, vycor filter,
C6H12, 72% H
1 : 2

4
1) LAH MeO
KOH 2) NaH; Me2SO4
substituted
(–)-CSA
cyclopentene
3) O2, photosensitizer, hn
Ac2O, Py, DMAP O

O
5 OMe

SnCl4, O
OH
CH2Cl2
–78 °C MeO
MeO
O OMe
73%
 Fukuyama Group - Group Meeting Problems
05/07/2003

1
O 1) 2,6-lutidine*, CH3CN, D, 88%
S p-Tol 2) n-BuLi; TMSCl, quant.
O
H S SO2p-Tol
3) MeLi (2 eq.); SO2, 75%

(*used as buffer)

2
1) dimethyl D-(–)-tartrate, Ti(Oi-Pr)4
t-BuOOH, CH2Cl2, –25 to –15 °C
n-Pent OH n-Pent
2) PPh3, NaHCO3, CCl4, reflux
OH
3) LDA (5 eq.), THF, –30 °C to rt

3 1) Rh2(OAc)4, CH2Cl2
AcO
O reflux, 93%
2) Et3N, CH2Cl2, 89% O
N2
3) Me3S(O)I, NaH, DMSO, 76%
4) Pb(OAc)4, AcOH, benzene OAc
reflux, 45%

4
1) BH3·NEt3 (1 eq : theoretical)
diglyme, D H OH H

2) CO (70 atm), HO OH
THF, 150 °C
3) aq. H2O2-NaOH H

5
CO2i-Pr OH
1) LDA, THF
–78 °C to 25 °C CO2i-Pr
O
2) decane, D
180 °C
Racemic
 Fukuyama Group - Group Meeting Problems
05/28/2003

1
O O
Me
cyclopentadiene H
OMe
PhI(OAc)2 hn

OH MeOH, rt acetone, rt O
H H
MeO OMe
79%
92%

2
1) O3, –78 °C
H 94% 3) Ba(OH)2·8H2O CHO
EtO2C
2) BF3·OEt2; MeOH, 0 °C
O CO2Me O O
H allyltrimethylsilane 64% (2 steps)
–78 °C

3 H3O+ O
72%
Mg (activated) AcOEt to –10 °C

THF –78 °C H3O+

rt 91%
to reflux OH

Li+
MgCl2 + Mg (activated)
THF
rt, 10 h

4 OH 1) NaBH4 (2 eq) 3) NaOMe

MeOH, rt MeO2C NHCOAr
MeOH, rt
O Ph
Ph
O N 2) MsCl (1 eq), Et3N 4) ArCOCl, Et3N
H CO2Me
CH2Cl2, –15 °C CH2Cl2, rt
CF3

Ar =
CF3

5 O

O 1) Li , Et2O, –78 °C, 1h CsF (3-4 eq.),

TBS TfO
(not isolated) PhNTf2 (2-3 eq.),

2) 0.5 eq. I2, THF, DME, 23 °C, 4 h OTf

O
–78 °C, 2 h, 74% 72%
(Sealed reactor)
O
 Fukuyama Group - Group Meeting Problems
06/04/2003

1 OMe
1) decalin, 215 °C, 1h TsNH-NH2
A O
2) HCl, EtOH, rt AcOH, CH2Cl2
CO2t-Bu 3) NaOH, H2O2, H2O/MeOH 72% CO2t-Bu
68% (3 steps)

O O
P(OMe)2
2 OTBS 1) N2 , K2CO3, MeOH, 88%
A
CHO 2) TBAF, THF
3) Swern oxdn., 76% (in 2 steps)

H O
t-BuLi,THF, –78 °C; cat. MeLi

CeCl3 (anhydrous); Ph2O, 185 °C H

Br A
76%
82%
3
Ts
Ph N
Ts
Ar
20 mol% PBu3 Ph N Ar
• CO2Et CH2Cl2, rt
CO2Et
Ar = 4-CN-C6H4
99% (dr 98:2)

4
2) Ph S
2
1) t-BuO2C CO2t-Bu
O Br t-BuOK
t-BuOK DMSO, rt; 3) NaOMe MeO2C
CO2Me
t-BuOH, rt LiBF4 MeOH MeO2C
benzene, rt reflux
82% 74%

5
n-BuLi (2 eq), THF, –40 °C;
O
Ph
Ph N cat. Hg(OCOCF3)2
MOMO
t-Bu Me O TFA
Me t-Bu
OTBS –78 to –40 °C; CH2Cl2 O
aq. KH2PO4 rt, 36 h O

74% 71%
 Fukuyama Group - Group Meeting Problems
06/11/2003

1 OH O NH2NHCOOEt;
SOCl2 K2CO3, BzCl
C8H6N2OS SBz
–78 °C to reflux acetone, reflux O

92% 91%

2 H
N
CO2Et
N O t-BuOK, DMF; N
MeHN CO2H (EtO)2P(O)Cl;
O
F F NMe
DMSO CN CO2Et
O 100 °C t-BuOK O

3 1) N2CHCO2Et
BF3•OEt2
O 2) NH2OH•HCl
AcONa, MeOH
OPiv OPiv
3) NaNO2, FeSO4
AcOH-H2O

MeO O 1) toluene
TMS 110 ºC, 70% 3) TFA O
•
MeO
2) Ag2O CH2Cl2
MeO OH OMe K2CO3 90% (2 steps)
benzene MeO OMe
OH

5
Pd (PPh3)4 O
H
• CO
OAc O
AcOH, 75 °C
22% H

racemic
 Fukuyama Group - Group Meeting Problems
06/18/2003

1
O
Pb(OAc)4

OH N NH2 THF
N
74%
NHCOPh Ph

2
MeO2C CO2Me
1) NBS, CCl4 (hn) DMAD
BnSiMe3 A N
2) MeNH2, MeOH toluene, reflux Ph N
83% Me
3) NaNO2, H+

3
OH
N
cat. p-nitrobenzonitrile, KOH CN
H
DMSO, rt, 5 hr, 79%
O2N HO

4
1) (PhMe2Si)2CuLi2I; Ac2O
2) O OH OH
CHO
CO2Et , SnCl
4
PhMe2Si Me Me
3) LAH; I2, PPh3, 78%
4) Zn, AcOH, 82%

5
1) SeO2, TBHP, CH2Cl2 O
OH 2) AllylBr, NaH, THF O
3) DBU (2 eq), toluene, 220 °C
4) TPAP, NMO, MS4A, CH2Cl2
dr > 98%
 Fukuyama Group - Group Meeting Problems
07/02/2003

1) n-BuLi (1 eq); ClCH2SCl

1 OH
Et2O, –78 °C to 25 °C
A
2) mCPBA (1 eq), CH2Cl2
25 °C, 47% (2 steps)

1) A, 60 °C 1) A, 60 °C

2) t-BuOK 2) t-BuOK
THF, 0 °C THF, 0 °C
57% (2 steps) 85% (2 steps)

2 OMOM
LiN O (2 eq)
Li O
HO
Br –78 °C, THF; –78 °C, THF;
Br A
Br isobutylaldehyde, reflux aq. HCl, ethanol, 0 °C Br

73% 75%

3 OH
O
MeO Me
TsOH O
O
acetone, reflux
HO
n-Bu 82% n-Bu

4
1) PhCH2N3
MeO OTES BF3·OEt2 O
47%
N
2) Rh2(OAc)4 Ph
90%

5 SiEt3
SiEt3
H O H
HO
a) t-BuLi, Et2O-pentane c) Li O I O
I –78 °C, 30 min; 0 °C, 1 h
–78 °C

b) Pr-C CCu, –78 °C to rt d) I2

 Fukuyama Group - Group Meeting Problems
07/16/2003

1 t-Bu
1) lithium dispersion HO
Si
TIPSO Me t-Bu2SiCl2, THF t-Bu
0 °C to rt OHC

TIPSO Me
2) O2N

NC
CH2Cl2, rt;
aq. HCl/THF 56% (2steps)

2 1) NaH; BuLi;
I 3) hv (Pyrex) H
O acetone/MeCN CO2Me
CO2t-Bu 87% 0 °C
O
2) TFAA (2 eq) 4) p-TsOH (0.1 eq)
TFA (25 eq) MeOH, reflux H
acetone, 25 °C 80% in 2steps
59%

3
N C N S Ph
HO O PhH, reflux;
O

Ph S Ph Ph

4 NaH, THF; 1) BnNH2

toluene, reflux*;
EtSCH2COCl Bn Me
TMS OMs
O NaI, : 73% TsOH N
CO2Me O Me
rt to reflux 2) NaIO4 benzene
MeOH-H2O, rt reflux CO2Me
87% EtS
90%
61%
*Dean-Stark trap
5
LDA; t-Bu CHO m-CPBA
A
TMS THF, 61% CHCl3, 77%
N

380 °C
A N
N
10 sec, 60% t-Bu
O t-Bu
O
1.7 : 1
 Fukuyama Group - Group Meeting Problems
07/30/2003

1 1) TiCl4;
OSiMe3

SiMe3 OPh Me3Si OH

O Me 2) TsOH Me
BnO
OSiPh3 CH2Cl2, –78 °C benzene, 40 °C BnO
80% (2 steps) O O

2 1) PhOPh
Cbz reflux, 60 min
N CO2Me 90% MeO2C

2) SeO2 (2 eq) N
HCO2H (2 eq) Cbz OH
dioxane, 90 ºC
4 hr, 68%

3
MsCl
, BF3•Et2O Et3N DBU
OH H O O
CH2Cl2 CH2Cl2 benzene
N –78 ºC, 2 h rt, 2 h 80 ºC, 70 h O
O PMP NHPMP
85% 74% 61 %
racemic

4
O O
1) acetylene, hn

2) p-TsOH, benzene
reflux

N 1) Rh2(OAc)4 (1 mol%) Me
N Ph
130 °C
O Me Ph
Ph
2) Me2AlCl HO Me
Me Me
 Fukuyama Group - Group Meeting Problems
08/06/2003

1) N2CHCO2Et, Pd(OAc)2
Et2O, 60% SOCl2
Cl
2) CH3ONa, CH3OH, 92% CHCl3
(single isomer) 74%
3) LAH, Et2O, 96%

2
CHO 2.5 mol% Rh2(OAc)4
S O H
ClCH2CH2Cl, reflux
3 days, 92%
Bz Bz S
The intermediate is the Rh-carbenoid complex.

3
1) HCl·H2NOH, Na2CO3, EtOH
reflux, 21 hr Zn, AcOH
CN reflux, 8 hr, 83% NHBn
2) TsCl, Et3N, CH2Cl2
H H 0 °C to rt, 1 hr; H H
BnBr, aq. NaOH, cat. BnEt3NCl isolated as HCl salt
reflux, 1 hr, 75%

4 Me
O N O O
O hν N N N N
N A N Me
O H benzene CH2Cl2 Ph N
Ph 25 °C, 10 min O
88% O OH
78%

5
PhO2S Me3Si
AlMe3
Me3Si
CH2Cl2, rt;
O work up
O
71%
 Fukuyama Group - Group Meeting Problems
08/20/2003

1 NH2
Me CN NaOMe (1 eq)
A NC CN
Me CN MeOH xylene
5 °C, 24 h (C13H16N4O) reflux, 3 h
Me N OMe
(2 eq) 86%* 99%

* Yield is based on NaOMe.

2
O 2) OTBS
1) N
Cl O
Ph sunlump (pyrex)
SH Et3N PhH, 91% CHO

THF 3) TBAF, THF, 94%

3
O 1) PhSeCH(CO2Me)2
hν 1) mCPBA CO2Me
C11H14O6
(bicyclic compound)
2) Bu3SnH, AIBN 2) Bu4NI, BBr3 MeO2C O
hν, 10 °C 3) CH2N2 O
O

4 TMSO n-Bu3SnH, AIBN

PhH, 80 °C;
OH
SiO2;
OTMS 1 N HCl, MeOH OH
49%

5
n C8H17 (s-Bu)3B n C8H17 n C8H17
+ + PhI
I Ph THF I
82% 14% 17%
BF4
 Fukuyama Group - Group Meeting Problems
09/03/2003

1
O
S S
POCl3, Δ ;
HN
N H2O N
H H
O

2
1) acrylonitrile OMe
Triton B 3) OMe 4) methylacrylate
CO2Me
THF, 96% LiClO4
SH
*R
2) mCPBA xylene, reflux , 45% CH2Cl2, rt S
CH2Cl2, 0 °C (diastereoisomer 24%) 88%
O
(= R*SH) 91 %

3
PhI(OCOCF3)2 O
Ph
Ph CO2H CH2Cl2 CO2H

86%

4
O O

hν
N CO2Me
benzene NH
O CO2Me O
50%

5
O Li
C6H13 SiMe3

Et2O, –100 °C
2 h; C6H13
ZrCp2 SiMe3
I2
–100 °C to –30 °C I
1h 60%
 Fukuyama Group - Group Meeting Problems
09/17/2003

1) n-BuLi 2) n-BuLi, I2
1 PhS SPh C10H12OS
77% 3) Na2CO3
MeOH LDMAN =
A
83% (2 steps) NMe2 Li

O 3) TMSCN Sn-Bu
1) A, LDMAN cat. ZnI2; O
Sn-Bu
2) aq HBF4 TBAF
64% (2 steps) 59%

2
Ph O
Ph 1) Ph2Cu(CN)Li2
H
THF, –40 °C to rt N
+N OTf– Ph
2) toluene, Δ H
O Ph

3 Ph
H Ph
toluene H
Ph O
O N 110 ºC
O N H
68%
OH

4 O O
OHC OMOM
O
pyrrolidine I
O O O
+
MeCN toluene O O
O reflux
80 °C
O O
2 : 1

5 OMe O OMe
1) O3, CH2Cl2
H –78 °C
MeO
MeO 2) FeSO4 O
Cu(OAc)2 O
OH
 Fukuyama Group - Group Meeting Problems
09/24/2003

1 O O

O 1) N2CHCO2Et
S Et2O, 77% CO2H
1) O2 , CH2Cl2; O , 73% 2) HCl, Et2O, 30%
S+ O- C8H10O3
2) O3, CH2Cl2, 64% 3) 20% aq. H2SO4
dioxane, Δ, 38% O

O
2 CO2Me
1) TMSN3, NBS, CH2Cl2
Ph A
2) heptane, reflux
PPh3

H Ph N CO2Et
N A
H H N
toluene Ph
Ph CO2Et reflux
CO2Me

3
1) Ph3P, DEAD
NsNHNH2, THF
Ph OH –10 °C to rt, 2.5 hr
84%
PMP
2) CAN, NaHCO3, MS4A
On-C8H17 TMS Cl(CH2)2Cl-MeCN (3:1 v/v) On-C8H17
40 °C, 10 min; TBAF
91%

4
BnMeN
NMeBn O
Ph CHO S O
N Ph
S +
MeO PhH, reflux * N
O 10 h, 74%
Ph PMP Ph
(* β:α = 7:3)

5 1)
OTMS
O OTMS
mesitylene, 190 °C 3) Collins oxidation O
(in a sealed tube), 63% 92% (in 2 steps)
MeO2C
2) NaBH4(2 eq), MeOH 4) FVT (470 °C, 1.5 torr) O
O rt 75% O
H
 Fukuyama Group - Group Meeting Problems
10/01/2003

1
1) n-BuLi (theoretically 1 eq)
OMEM THF, –78 °C; Bu3SnCl O
–78 °C to rt, 59% A BF3·OEt2
Ph
SO2Ph 2) benzoyl chloride, toluene Dihydrofuran CH2Cl2
O
reflux, 83% –78 °C to rt
racemic 45%

2
1) LDA (1 eq), THF; MeI
–78 °C to 0 °C, 95%
2) toluene, reflux
S N
3) LDA (1 eq), THF; Br
S (all trans)
–78 to 0 °C, 90%
4) MeI, LiF, Li2CO3
DMF, rt (in the dark), 80%

MeO O O 1) TsOH•H2O
MeOH-H2O 3) K2CO3, MeOH MeO2C
reflux, 70% reflux, 88% N
C13H19NO3 H
2) toluene, reflux 4) SmI2, THF HO H
N 64% rt, 64%
O HO
O O

4
O Et
S Ac2O, DMAD OH
cat. TsOH CO2Me

O xylene, reflux
CO2Me
NEt2 NEt2

5
R
R
I cat. Pd(0)
+ R R + PhB(OH)2
Ph
 Fukuyama Group - Group Meeting Problems
10/08/2003

1 F F Zn, TMSCl F F
O MeCN, 100 °C, 20 h OH
Cl
; wet SiO2
O O
78%

2
O
N3 BF3•OEt2 N O
CH2Cl2
rt, 2 min
92%

MgX KHMDS KHMDS

O
THF toluene, 50 °C diglyme, 100 °C
Ph
O Ph
79% 67%

1) pyridine, benzene 2) PhMgBr, THF NHTs

rt, 1 h; –60 °C, 1.5 h
Ts-N=S=O
3) (MeO)3P, MeOH
reflux, 30 min NHTs
rt, 15 h 83% (2 steps)
43%

OMe OMe O
1) OMe MeO
O2 N Me 2) hν OMe
Li

80% MeOH Me N
OHC OMe
45% OMe
OMe HO
 Fukuyama Group - Group Meeting Problems
10/15/2003

1
1) PPh3;
N
O Ph
Me O Ph
Me 2) NaBH4
Me
Ph N
benzene glyme H
Ph Ph 85% 70% Ph Me

2 S 1) NaBH4, EtOH;
MeI, Na2CO3 S
S hυ, Pyrex rt, 69%
O A S
S benzene 2) MeI, Na2CO3
76% EtOH, reflux S
S 72%

3
Bn N Ph
n-BuLi; PhCN
N N
N THF toluene
N –78 °C to rt reflux Ph

4
MeS O
N + n-BuLi
O n-BuSH S
TsOH
OH
benzene THF
reflux –70 °C;
Dean-Stark Silica gel, 4 N HCl

5
MeO O
1) PhLi 2) TsOH, H2O OH
O (workup H3O+)
Me Me
 Fukuyama Group - Group Meeting Problems
10/29/2003

1
O
3) NaOH, H2O2
1) TMSCN, ZnI2 (cat.) n-Bu4NHSO4 O

2) POCl3, pyridine 4) 3N HCl

reflux

2
1) hυ (350nm) Me CO2Me
N PhCOCH3/acetone H

2) Me2CuLi O
O N
MeO2C

3
Ph Ph
1) xs. TFAA, xs. Py
CH2Cl2, 0 °C, 85% CN
2) Me3Al, NH4Cl
N PhH, rt; t-BuOK, 94% N
O Me Me

4
O H
N
O Ph
N
benzene, 406 °C Ph +
Ph
N O
14% 13%

5
S
1) S2Cl2, Et3N, Et2O (98%)
OH S O
2) CHCl3, reflux (69%)
O
 Fukuyama Group - Group Meeting Problems
11/05/2003

1
1) NaH;
O O n-BuLi; NaNO2
PhCHO FeSO4 Ph
EtO Me A Ph
2) NH2OH·HCl AcOH-H2O OH
Ph AcONa
87%
48% (2 steps)

2
H H
30% H2O2
PhSe
O
O EtOH
H H
reflux O

3
O
1) cat. CuCl, Cl
CH3CN, 115 °C, 76% cat. Et3N aq. NaOH Cl CO2H
CCl4 C8H10OCl4 C8H10OCl4
2) , Et3N toluene rt to 100 °C Cl
cyclohexane, 65 °C reflux 73%
67% 90%

SnCl4
O
CH2Cl2, –20 °C
OH
O O
94 %

5
H Ph 1) POCl3
N H iPr2NH N

O Pd(PPh3)2Cl2 2) tBuOK
I
CuI, Et3N tBuOH
99%
 Fukuyama Group - Group Meeting Problems
11/12/2003

1
3) MgX
Ph Ph 1) I(coll)2ClO4
medium toluene, rt OH
OMe
HO membered 86%
O O
CH2Cl2 ring
compound 4) Ca, NH3
–78 °C to rt, 77 % OH
–78 °C, 92%
2) LAH, THF
72%

2
CO2Et NH•HCl CO2Et

N N NH2 N N
DMF, 90 °C, 24 h
EtO2C N CO2Et H2N CO2Et
85%

3
1) KH(ex), THF, rt;
OH ClCO2CH3, Py, –78 °C to rt; O
KOH, MeOH-H2O, rt, 70-90%
NHCH2CN
2) HCO2H, reflux, 65% N
MeO2C

4
Me Me
TFAA (5 eq)
Py (10 eq) Ar =
N N
COAr COAr Me
benzene
CO2H 12 h, rt COCF3

55%

5
O TsNH2, NCS aq. 6 N HCl O NHCOCHCl2
heterocyclic
Ph Ph CH3CN, 50 °C; compound THF Ph Ph
NCS (2 eq) 70 °C NHTs
 Fukuyama Group - Group Meeting Problems
11/19/2003

1 Me
Me 2) (PhCO2)2 3) K
1) hν (Vycor filter) CH3CN 18-crown-6 Me
Me
Me H
O O cyclohexane reflux toluene O
15% 67% 90% O Me

2
O
N2C(CO2Me)2,
Rh2(OAc)4 , BuSSBu 1) m-CPBA, CH2Cl2

TMS 100 °C hν 2) H2SO4, MeOH MeO2C

64% MeO2C
79% 79% (2 steps)

3 1) Piv2O, TMSOTf O
O
O CH2Cl2, –45 ºC 3) TBSOTf, 2,6-lutidine
O 54% C26H38O8 CH2Cl2, 0 ºC, 72%
β-hydroxy ketone
2) hν, Et3N 4) Et3N, MeOH
O HH HH
MeCN, 78% 60 ºC,70%
O O OTBS

4
NH2
MeO Me
1) NaNO2, aq HCl, 0 °C; 2) HCl, EtOH, heat

KOH, O N CO2Et
CO2Et H
Me
OMe
Et

5
CO2Me Ph
TfOH
C10H9NO3
NO2 toluene
CHCl3 O Ph
90 °C
50 °C
(C10H11NO4)
 Fukuyama Group - Group Meeting Problems
12/03/2003

1
O 1) HCO2Et, NaOMe, 84% CO2Me
H H 2) TsN3, Et3N H H
rt, 80%

3) hν, MeOH, 71%

H H
OH OH

2 O
1) 1) AgBF4, Al2O3, CCl4
Cl , Et3N 2) TsOH, benzene, 80 °C

2) SeMe 3) hυ
Li
ether-pentane

3 1) P(OEt)3 (3.0 eq.), PhMe

reflux, 7 hr
TBSO 2) TMSBr, PhMe TBSO
H H H H
10 °C, 2 hr, 87% (2 steps)
COSEt
N CO2Et 3) Pd/C, Et3SiH, CH2Cl2 N
O 10 °C, 1 hr, 57% O
O 4) DIPEA, LiCl, MeCN CO2Et
25 °C, 17 hr, 88%

4
PhHN NO2
PhHN NO2
1) DEAD, DMF, 97%
PhN NHPh
PhHN NHPh
2) PPh3, CH2Cl2, 0 °C; Ph O
S PhCO2H, 67% O

5 Br Br
KCN (> 1 eq) HO2C HO2C
+
O2N H2O, EtOH, 150 °C Br
sealed tube
40% trace
 Fukuyama Group - Group Meeting Problems
12/17/2003

1 O– O
Et2NH (2 eq)
O
AcOH (0.5 eq)
S+ + R CHO R
Ph propanenitrile*
(2 eq) OH
rt, 6 h
R = n-Bu
* Used as a solvent 82%

1) Al(Oi-Pr)3, i-PrOH
2 1) hν (pyrex) reflux, 91%
O 2) TsCl (1.3 eq) H
acetone HO
5 °C, 88% pyridine, rt, 89%
Tricyclo Me
Compound 3) i-PrLi (5 eq)
2) 4% aq. KOH
AcO Me rt, 100% pentane, rt, 55% Me

3 TESO Pd(PPh3)4 O
CO (800 psi) O
OTf OTES
R i-Pr2NEt
R O
PhCN
HO O 65 to 110 °C

56%
R=

4
SiMe3 Ti(Oi-Pr)4 SiMe3
i-PrMgCl (2 eq) Et
O Et2O, –78 to 0 °C OH
H OH
O

5
O
Bu3SnH, AIBN O
COOMe
I PhMe, COOMe
MeO
74%
MeO MeO
OMe
 Fukuyama Group - Group Meeting Problems
01/07/2004

1
Pd(dba)3•CHCl3 (2.5 mol%) O
O diphenylphosphinoethane silica gel
O OMe
methyl acetoacetate
THF, rt

75%

2
HO Cl O
NO2 t-BuOK (in t-BuOH) SmI2 (4 eq), t-BuOH HN
THF THF CHCl3
0 °C to rt, 0.5 - 1 h 0 °C, 10 min –20 °C, 48 h O

78% 60% 92%

3
1) O2, Rose Bengal; Me2S
CH2Cl2-MeOH, –78 °C, 5 h
O
2) CF3CO2H O
CH2Cl2, rt, 14 h
OH O
62% in 2 steps

4 Li–SiMe2Ph
O
O
THF, –78 °C; Me2N
NMe2
Li
O

NEt2 71%

–78 to –20 °C

5 Bn
OH
AcO NsHN COOt-Bu 1) TFA, rt, 96% O OH
O Ph3P, DEAD 2) KOt-Bu, MeOH, 93% HO
AcO Bn
AcO OH OH
OAc THF, –80 °C 3) PhSH, DIPEA N COOH
DMF, rt, quant. H
98%
 Fukuyama Group - Group Meeting Problems
01/14/2004

1) BzOCH2CHO
1 OH BF3•OEt2, CH2Cl2 3) LHMDS; PhSeCl H
–23 °C, 71% THF, –78 °C, 88% 5) NaOMe MeO2C O

2) mCPBA 4) O3; Py, CH2Cl2 MeOH, rt O OH

OH CH2Cl2, rt, 87% 83% H
–78 °C, 80%
dr=12:1

2 Br O
1) Br
Cl 3) Zn 5) BF3•OEt2
AlCl3, CH2Cl2 THF-phosphate buffer CH2Cl2
rt, 80% S S
rt, 87% rt, 93%
MeO2C
O2S O
2) HS SH 4) xylene 6) DMAD O
reflux, 74% toluene MeO2C H
p-TsOH, benzene
reflux, 87% reflux, 83%

3
(Me2Al)2Se O
OMe
O anthracene
CO2Me
Ph
Ph H toluene toluene
100 °C 160 °C

1) Me2NCH(OMe)2
4 O
O dichloroethane; O
O
HO evaporation;
Ac2O, 100 ºC, 68% O
HO
O O
2) LHMDS, t-BuOOH,
OH THF, 0 ºC, 77% OH
O O

5
Me O Me OH
N
NOCl hν
Me H OH Me H O
pyridine EtOH
H H H H

H H
 Fukuyama Group - Group Meeting Problems
01/21/2004

1
MeO2C Me
1) MeN3, toluene, rt, 73%
2) hν, pyrex, dioxane, 89% N
O N O
3) methyl acrylate
Bn hν, quarts, dioxane, 59% O N O
Bn

2
O 1) BF3·OEt2, THF, 70%
LDA, DPPCl*, THF; (isolated as salt)
N O
NaN3, DMF 2) 30% aq. NaOH, 68%
Ph N
3) H2O, THF, reflux, 82%
83%

(*DPPCl = diphenyl phosphorochloride)

3
1) i-AmONO, t-BuOK 3) hν
O t-BuOH, rt dioxane-Et2O-H2O CO2Me
o.n., 79% 48 hr
H H
2) aq. NH3, NaClO 4) CH2N2
H H MeOH-H2O MeOH-Et2O (3:1 v/v) H H
0 °C to rt rt, 1 hr
HO 39-41% (2 steps) HO
6 hr, 55-64%

4
H
THPO OH TsOH, MeOH; 1) MeNO2, TritonB O O
CO2tBu Me O
Me TsOH, benzene 2) TiCl3, Et3N
Me reflux H
Me

5
O O3, vinyl acetate (7 eq), –78 °C, CH2Cl2; O O

CH2Cl2, reflux, 12 h, a (56%), b (26%)

Hexane, reflux, 12 h, a (15%), b (63%)
CHO OCHO
a b
 Fukuyama Group - Group Meeting Problems
02/18/2004

1
TpRu(PPh3)(MeCN)2PF6 (10 mol%)
LiOTf (20 mol%)

toluene
OH reflux, 5 h

88%
Tp: tris(1-pyrazolyl)borate

2
O 1) PhNHNH2, EtOH
2) 10% H2SO4aq, reflux hν
70% (2 steps) (mercury lamp) NH
O
3) DPPA, Et3N ether N
HO2C CO2H PhH, reflux; BnOH, reflux H
4) H2, Pd-C 89% (3 steps)
AcOH-MeOH-H2O

3 1) n-BuLi; p-CH3C6H4CO2Me
THF, –78 °C to rt n-BuLi (xs)
BtCH2SPh p-CH3C6H4
2) TsNHNH2, cat. Amberlyst-15 Et2O, –78 °C to rt
benzene, reflux
(Bt = benzotriazol-1-yl)
as above
BtCH2OPh p-CH3C6H4 n-Bu

4
O
O 1) Zn-Hg, conc. HCl 3) mCPBA, TFAA N
N reflux, 76% CH2Cl2, 70% O
O C17H21NO3
2) PdCl2, CuCl2, O2 4) FeSO4, O2
O 0.2 N HCl-DMF AcOH
65 °C, 74% 100 °C, 57% O

5
S
i-Pr
S N i-Pr
O– TiCl4
+ NaN S
S+
Ph Ph CH2Cl2 S N
S rt
i-Pr
 Fukuyama Group - Group Meeting Problems
03/03/2004

1 1) mCPBA 1) TBSCl, Imid.

O
O CN
CH2Cl2, 91% DMF, 99% O
Br C16H12BrNO2 Br
2) KOt-Bu 2) LHMDS, O2;
DMF, –57 °C; SnCl2, 94% TBSO
aq. HCl, 54%

2 1) SOCl2, Et3N (2.1 eq.)

xs. 1,3-butadiene I
Et2O NIS, AcOH
MeO2C CO2Me C9H12O4S CO2Me
2) Tf2O, NaI (2.4 eq) CHCl3, 5 h S CO2Me
acetone, 0 °C AcO
70% (2 steps) 90%

3 OPh SO2Ph
OPh BuLi, THF, –78 °C; TsOH

PhCOIm, –78 °C to rt CH2Cl2 PhO Ph

SO2Ph 14 h O
82%
90%

1) PhNHOH
4 COCl K2CO3 3) aq.KOH HO2C
ether, 74% EtOH;
HO NH2
Cl aq.HCl
2) KOH
NO2 EtOH, rt 76% O2N
90%

5 Oi-Pr O O O
Oi-Pr
i-PrO
O O O
POCl3;
NMe O NMe NMe
O NaBH4, MeOH O
CHO
O O
22% 44%
 Fukuyama Group - Group Meeting Problems
03/10/2004

1 1) Mn(OAc)3
3) NaN3, Tf2O
Cu(OAc)2
KOAc, AcOH 2 N NaOH, Bu4NBr O Ph
O 70 °C CH3CN-hexane, 0 °C
H H
2) BnOH 4) Rh2(OAc)4, CH2Cl2
Ph O O Ph O
Mg(ClO4) O
120 °C

2
O O
N O N
DMAD HCl aq. Δ
N CHO
N toluene DMF N N
95 °C
O N N 95 °C reflux H
O
56%
56% quant.

3
PhI (10 eq) i-Pr Ph
Ag2CO3 (2 eq)
PhO2S
Pd(OAc)2 (10 mol%)
PhO2S
i-Pr
DMF, 120 ºC
69%

4
NC
O
NaN3

MsOH, 0 °C

60% OMs

5 CO2Me
N 1) PPh3, toluene, reflux CO2Me

Ph CHO 2) DMAD, toluene, 140 °C

N Ph
Y. Kaburagi
 Fukuyama Group - Group Meeting Problems
03/24/2004

1
O O
CO2Et KH, SeO2Ph

THF, rt CO2Et

2
1) benzaldehyde
2) SO2Ph
PhO2S
O
NHOH CH2SO2Ph
benzene, 80 °C

3) DBU, benzene N
H Ph

3 1) CHBr3, CH2Cl2
aq NaOH (MeCO)2, hν CO2H
phase-transfer cat., 45% 58%
Cl Cl C5H6
2) MeLi (2 eq), –78 to 0 °C 3) Br2, aq NaOH HO2C
Et2O-pentane; 1,4-dioxane, 90%

4
S
S Ph-N=O O O
O CH2Cl2, 3 days N
Ph
quant.

5 1) KOH
O THF-H2O (1:1 v/v)
LTA, PhH reflux, 14 hr
O
PhS O reflux, 1 hr 2) LTA, NaOAc O
H 91% AcOH, 2 hr H
O 50% (2 steps) O
 Fukuyama Group - Group Meeting Problems
04/07/2004

1 O
N3
O O LDA (2.0 eq) then, PPh3 H
N OEt
Me OEt THF THF THF O O
0 °C, 1 h –78 °C to rt,12 h 45 °C, 24 h
57% 60%

2
O
Tf2O, Pyr; N
N
H2NCH2CH2SH S
H

3
CN CH2CO2Et
NO2
DBU

N THF N N CO2Et
H
PhO2S PhO2S
85%

4
Br NaH
CO2Me THF-DMSO
t-BuOK rt, 30 min;
C18H16O3S
CO2Me THF-t-BuOH MeI O
rt, 3 h 35 °C, 3 h
SO2Ph
51% 90%

5 1) NaH
allyl bromide, THF

N 2) 9-BBN, THF, rt; N

H NaOMe (1.2 eq);
t-BuLi, TMEDA, –30 °C to rt;
allyl bromide; 58%
30% H2O2 aq. NaOH
 Fukuyama Group - Group Meeting Problems
04/13/2004

1
H
KHMDS
O
THF
OH 20 °C
4 days
OMe H
S. L. Schreiber et al., J. Am. Chem. Soc., 101, 2331 (1989)
2
OMs 1) TMSI (1.1 eq) Me
Me H
Me HMDS (1.2 eq) 2) MeMgI (5.0 eq) Me
Me
Me pentane toluene HO Me
O –20 °C to rt, 8 h rt, 30 min
H Me Me H
60% (2 steps)
A. Groot et al., J. Org. Chem., 66, 2350 (2001)

3 1) (HO)2B OH
Pd(PPh3)4, TlOEt
THF-H2O, rt, 63% RhamO H
RhamO H
COMe 2) Dess-Martin periodinane, Py H
CH2Cl2, 0 °C to rt TBSO
TBSO
3) (CF3CH2O)2P(O)CH2CO2Me Br
COMe
Br Br KHMDS, 18-crown-6 H
THF, –78 °C, 57% (2steps) CO2Me
Me 4) t-AmOH, 40 °C;
Rham = O PMe3, rt, 89%*
O OMe
*desired : undesired = 96 : 4
MeO OMe W. R. Roush et al., Org. Lett., 4, 3157 (2002)
4

CO2Et
1) PPh3 , THF, rt
CO2Et
2) Br2, CHCl3, –20 °C
3) DBN, benzene, reflux
W. Dauben et al., Tetrahedron Lett., 38, 3711 (1973)

5 Boc 1) LDA, ether

N 0 °C, 52%
NBoc
O 2) KH; CS2; MeI
THF, 0 °C
3) Bu3SnH, AIBN
toluene, 100 °C
60% (2 steps)
D. M. Hodgson et al., J. Chem. Soc. Perkin Trans. 1, 3150 (2001)
 Fukuyama Group - Group Meeting Problems
04/21/2004

1
O-
NH2 1) n-pentyl nitrite, 3-hydroxypyridine Ph N+
diglyme, reflux OH

CO2H 2) mCPBA, CH2Cl2

A. R. Katrizky et al., J. C. S. Perkin I, 2334 (1976)

2
L. E. Overman et al., J. Org. Chem., 50, 2403 (1985)
Ph3SnH
Me2ClSiCH2Br AIBN KHCO3
n-BuLi DMAP, Et3N acrylonitrile H2O2 CN
n-C5H11 n-C5H11
THF CH2Cl2 benzene MeOH / THF HO
O –78 °C rt reflux reflux
HO
90% 51% (2 steps)
M. Malacria et al., J. Org. Chem., 57, 3085 (1992)

3 O
O
neat
O
SMe2 170 °C
5 min
O
33%
Y. Kita et al., Tetrahedron Lett., 26, 2351 (1973)
4
H
1) NaNO2, HCl, CuCl, MeOH, 0 °C to rt, 81% H
2) H2C=CHCH2Si(Me2)CH2MgBr, BF3·OEt2
N CuBr2-Me2S, Et2O, –78 °C to rt, 87% HO
N
O 3) BF3-HOAc, CH2Cl2, rt;
35% H2O2, NaHCO3, MeOH, THF, 95% Ph O
NH2

S. M. Weinreb et al., Org. Lett., 3, 3507 (2001)

5 1) MeO2CN S NCO2Me
toluene, rt 3) NaBH4
O
88% MeOH, 91%
HN NH
2) toluene, reflux 4) NaH, THF;
SBn 98% aq.NaOH BnS
89%

S. M. Weinreb et al., J. Org. Chem., 53, 1116 (1988)

 Fukuyama Group - Group Meeting Problems
05/11/2004

1
BF3·OEt2
SiMePh2
CHO CH2Cl2
+ TBDPSO CHO + TBDPSO
BnO -78 ˚C -r.t (2 h)
SiMe2Ph O OBn
then r.t. 5h
48%

T. K. Sarkar et al., Angew. Chem., Int. Ed., 43, 1417 (2004)

2 1) PPh3
80 °C, 3 days
80-90%
S 2 2) Mg F 2
THF
reflux Br
3 h, 90%
3) Na, liq. NH3*, 95%
(Condition for Desulfurization)
W. D. Oilis et al., Chem. Commun., 99 (1969)
3 O
NaOH
30% H2O2
then
BH2Cl (1 eq) Cl2CHOMe (1.1 eq) EtOH-H2O
THF, 0 °C; LiOCEt3 (1 eq) 50 °C
85%
MeOH (1 eq) THF
(2 eq) 0 °C 0 °C to rt AgNO3

EtOH-H2O
83%
H. C. Brown et al., J. Org. Chem., 40, 813 (1975)
4
1) Tf2O (2 eq) 3) O3; Me2S CO2H
i-Bu3N CH2Cl2
40 ºC, 82% –78 ºC, quant.
Cl
Cl 2) TfOH (1 eq) 4) 10% NaOH aq.
O CH2Cl2 rt, 92%
–78 ºC, 98%

A. G. Martinez et. al., Tetrahedron Lett., 42, 7795 (2001)

5
TBSO Me TBSO
Me n-Bu3SnH Me
AIBN(cat) Me
O O O
Br benzene, 80°C O
(75%)

J. L. Mascarenas et al., Org. Lett., 3, 1181 (2001)

 Fukuyama Group - Group Meeting Problems
05/19/2004

1 O
CO2H SOCl2, Py i-Pr
1) DBU, toluene, reflux N
benzene, reflux, 1 h; 0.5 h
O

i-PrHN CO2Et 2) xs. BF3•OEt2

toluene, reflux F
Et3N, CH2Cl2 CO2Et
rt, 16 h
F
公開特許公報（A）平3-279362, US Patent 5189043 A

2
Bn NC
CONHBn
CO2H
N
N Bn N Bn
Ns MeOH toluene
rt, 36 hr reflux, 18 hr NsHN
O
85% 65%

K. Paulvannan et al., J. Org. Chem., 69, 1207 (2001)

3 1) NH2OH·HCl
O NaOAc, MeOH Me H
H 2) NaBH3CN, MeOH N
Me
3) (HCHO)n, MS4A HO
Me tol, reflux
H
4) MeOSO2F, ether, 0 °C
5) LAH, THF
W. Oppolzer et al., J. Am. Chem. Soc., 98, 6722 (1976)

4
OH OH
DMSO, DCC
Me H3PO4 Me
SMe
65%

R. A. Olofson et al., Tetrahedron, 27, 4181 (1971)

5 MeO
MeO O
N2 hv O
THF

80%

B. M. Stoltz et al., J. Am. Chem. Soc., 125, 13624 (2003)

 Fukuyama Group - Group Meeting Problems
06/01/2004

1
OMe MeO2C CO2Me
N N DMAD (1 eq)
O
O MeO2C
benzene, reflux
MeO MeO
60%

J. Warkentin et al. Tetrahedron Lett. 40, 1483 (1999)

2
R
PhI(OAc)2
OMe allyl alcohol R
KH, 18-crown-6 H2, Pd/C
Cl2Ce

OH CH2Cl2 THF, –78 °C THF, reflux MeOH O

H
O OMe
77% 76% 97% 95%

O O
R=
C. -C. Liao et. al., Org. Lett., 5, 4741 (2003)
3 MeO2C
O CO2Me
DMAD (2 eq)
PPh3 (1 eq)
N OH
N CO2Me
CH2Cl2, rt, 24 h
O
95% O
I. Yavari et al., J. Chem. Res. (S), 166 (1998)

4
1) 1M HCl, THF
(10 eq) rt, 3 h CO2H
O cat. hydroquinone 43% (2 steps) t-BuOK
EtO C8H10O
OMe 80 °C, 24 h 2) 5% NaOH t-BuOH
reflux, 6 h 185 °C Ph
74% 60%

J. B. Stothers et al., Can. J. Chem., 55, 4184 (1977)

5 O
O
1) acrolein, PPh3, MeOH, rt, 30 min;
NO2 O
NaBH4, 0 °C, 30 min; 2) Zn, HCl

NaOH, 0 °C, 30 min; toluene

3 M HCl, 0 °C, 20 min 0 °C

72% 84%

S. Stanchev et al., Tetrahedron Lett., 34, 6107 (1993)

 Fukuyama Group - Group Meeting Problems
06/09/2004
1 O
2) EtSH (3 eq*)
1) P Cl
O NaH (3 eq*)
OH Et3N, ether; DMF, reflux; NHBn

benzylazide aq.HCl
xylene, reflux MeOH, rt
70% 90% *theoretical amount 2 eq

A. K. Mapp et al., J. Am. Chem. Soc., 126, 5364 (2004)

2
Na ( 4.0 eq); O Ph
BnHN CN (1.1 eq) (2.5 eq) AgNO3 (1.1 eq)
CO2Et TMSCl(4.0 eq) Ph Li
EtO2C
Et2O MeOH THF 50 °C N
reflux rt -78 °C H Bn
93 %
70 % 75 % 58 %
Org. Synth., Coll. Vol. V1 1988, 167
L. E. Overman et al., J. Org. Chem., 50, 2403 (1985)
3
1. xs EtONa
O
Cl Et2O, reflux Me O
then
Me
solvent exchange
CO2Et
H to benzene and reflux H
2. 10% HCl, reflux

G. Stork et al., J. Am. Chem. Soc., 82, 4315 (1960)

4 O

N sealed tube tetracyclic

compound
toluene
O 200 °C
N
Ac 77% O
3) NBS, CH2Cl2 N
1) NaBH4, EtOH, rt rt, 66%

2) TBSOTf, 2,6-lutidine 4) n-Bu3SnH, AIBN

CH2Cl2, 0 °C to rt benzene, reflux N
91% Ac OTBS
60% (2 steps)
A. Padwa et al., J. Org. Chem., 69, 3735 (2004)
5
1) dichloroacetyl chloride 3) N-bromoacetamide NC
Et3N, hexane, 85% BnOH, 85-95% O
2) Zn dust, AcOH 4) sat. KCN in MeOH
70 °C, 95% NaOMe (cat.), 85-90% BnO

S. M. Roberts et al., J. Chem. Soc. Chem. Commun., 948 (1974)

 Fukuyama Group - Group Meeting Problems
06/23/2004
1 Ts
Ts
N
N p-TsOH (0.1 eq)

benzene Ph
S Ph reflux S
O Me 10 hours, 73%

Ts
N as above Ts
N
Ph
S Ph S
O Me
3 days, 34%
H. Shimizu et al., Heterocycles, 22, 1025 (1984)
2
H Me Me
OH
BF3·OEt2
O
Et2O
–10 °C H Me
Me
T. Matsumoto et al., Tetrahedron Lett., 26, 873 (1985)
3
1) cyclopentadiene
hν, CH2Cl2
20 °C, 76%
O C15H22OS = catalyst A
Ph
S 2) H2, Pd-C
EtOH, rt, 84%
O
catalyst A (5 mol%)
BnNEt3Cl (5 mol%)
O Na Rh2(OAc)4 (1 mol%) O Ph
+
Ph H N Ph
Ph N Ts CH3CN
1 eq 2 eq 82%

V. K. Aggarwal et al., Angew. Chem., Int. Ed., 40, 1430 (2001)

4
OBn OBn OBn
N3
O MeO P N(i-Pr)2 O
HO
tetrazole
OMe O OMe
OBn OBn
Z. Guo et al., Org. Lett., 6, 1365 (2004)
5
OMe NTs
TsHN HCHO
OMe
OH BF3•OEt2
MeO HBr MeO O
O AcOH CHCl3 O

64% 90%
A. Garcia et al., Tetrahedron Lett., 42, 665 (2001)
 Fukuyama Group - Group Meeting Problems
06/30/2004

1
O O
Li (2 eq) H
i-PrO O 10% H2SO4 H
O
THF, –78 ºC, 5 min; overnight
i-PrO O xs. vinyl lithium, 0 ºC, 2 h; rt i-PrO OHH O
rt, 16 h; Oi-Pr
degassed NH4Cl aq. 24% (2 steps)

J. Am. Chem. Soc., 124, 9199 (2002)

2 OMe O
O
NH2 COOH N
TfOH

AcOH, 6 d; 110 °C H
N evaporation; 45 min
H N
NaOH, MeOH
84% 46%
M. Node et al., J. Am. Chem. Soc., 109, 7901 (1987)
3
I– 1) NaNH2, liq. NH3, 46% N
N
2) MeI, MeCN-Et2O, 93%
3) NaNH2, liq. NH3, 66%
D. Barbry et al., Tetrahedron, 47, 47 (1991)
B. Hasiak et al., Tetrahedron Lett., 31, 5769 (1990)
4
1) OEt
CO2H
NH •HCl
H2N OH
Et3N 6-membered 1) phenol, TFA NH2
ring HO
Ph Ph 2) SeO2 2) H2, Pd(OH)2
TFA (mixture of o- and p-)

F. Lei et al., Synlett., 1160 (2003)

5
1) NaH, CH3C C CH2Br
DMF, 95%
CN
2) LiAlH4-AlCl3 (1 : 1), Et2O,
MeO 0 °C, 92% MeO
CH3
COPh 3) MCPBA, CH2Cl2, 0 °C;
N N
H evaporation; CH2Ph
xs. KCN, DMF, 50 °C
50-70%
Y. Makisumi et al., Chem. Pharm. Bull., 24, 770 (1976)
 Fukuyama Group - Group Meeting Problems
07/07/2004

1 N Cl H
O C O N
CN O 1) K2CO3
NaH DMSO, 65% CO2Et
THF 2) EtOH CN
reflux, 63%
74%

2
NH2
NC CN S CN
NC
NH2 Et3N (cat.) CN
+
EtOH, rt Ar
Ar CN
76%

Ar = 4-MeOC6H4

3
O
-O N+
Cl O
O
Ph3P AgBF4; KCN t-BuOK

H2O/CH2Cl2 t-BuOH
rt, 20 min 80 °C, 2 h

4 O O
Me3SnSnMe3 N
N
+ N
CO2Et 80°C, hv
NC Br
CO2Et
Et (63 %)
Et

5 OMe
3) , CO O
OMe
Me4N 1) AcBr, CH2Cl2
–78 °C O
O THF, 80 °C, 3 d
(OC)5Cr 2)
OH 4) aq. HCl
Me
 Fukuyama Group - Group Meeting Problems
07/13/2004

1
1) Ph CHO
EtOH, 80% Ph
"Isolable Species" N
N Me 2) hν (pyrex) toluene O
PhH, rt, 88% reflux
O
71%
W. Eberbach et al., J. Chem. Soc., Chem. Commun., 301 (1994)

2 xs. aq. H2O2

HO Na2CO3 (1.5 eq) 1) TsCl (1.1 eq)
H
HO O O activated carbon pyridine, 84% O
C4H6O4 HO
H2O; 2) EtONa CO2Et
HO OH HCl EtOH-THF
91%
94%
L. O. Weigel et al., J. Org. Chem., 56, 6225 (1991)
H. L. Frush et al., Carbohydr. Res., 72, 301 (1979)

3
Me
O 1) 98% H2SO4, MVK
O
–78 °C to rt, 77% 1) H2, Pd/C
MeO2C Br
2) O
2) t-BuOK
18-crown-6
(MeO)2P Li (1.3 eq) OMe
tol, 80 °C
THF, 0 °C, 70% 64% (2 steps)
G. A. Kraus et al., J. Org. Chem., 55, 5423 (1990)

4
O
NH2OH
O

EtOH
H+ N
O H

F. M. Dean et al., J. Chem. Soc, 5096 (1964)

5 O
O O
Ph Cl , Py PhNHOH
O O Ph
CH2Cl2 MeCN xylene N
reflux reflux H

93 % 67%

O. Yonemitsu et al., Tetrahedron Lett., 33, 1459 (1992)

O. Yonemitsu et al., Chem. Pharm. Bull., 30, 3097 (1982)
 Fukuyama Group - Group Meeting Problems
07/28/2004

1 3)
O
1) mCPBA* MgBr, CeCl3
CH2Cl2, 0 °C THF, –78 °C to rt, 74%
TBSO TBSO
2) 10%HBF4 aq 4) PdCl2(CH3CN)2
CH2Cl2, rt H
DME, rt, 81%
86% (2 steps)
α:β=6:4
*theoritically 1 eq
H. Nemoto et al., J. Org. Chem., 62, 7850 (1997)

2
H Et
CO2Et
O Et • CO2Et
Ph H N
N
O benzene
O reflux, 14 h
60% O
HO

M.P.S. Ishar et al., Tetrahedron. Lett., 40, 175 (1999)

3
O OMe O OMe
O NaCN (1.1 eq), rt, 1 h;
TFAA (1.2 eq) O
(1.0 eq); (1.0 eq); O
–78 °C to rt, 1 h;
ThxBH2
THF rt, 3 h mCPBA (2.3 eq)
0 °C, 1 h 10 °C, 30 min
80%

Delter, A. et al., J. Chem. Soc., Perkin Trans. 1, 110, 129 (1975)

4
1) O OH

MeLi (1.05 eq) Ph Me

Et2O; ZnCl2, CH2Cl2 Ph
TMSCl (1.02 eq); 91%
OEt
filtration; 2) NaH, DMF Me O O
120 °C (distillation) 0 °C, 82%

65% Y. Kita, et al., J. Org. Chem., 55, 1108 (1990)

5 O
Pd(PPh3)4 O
HO OH
P(o-tolyl)3
R THF R
R reflux R
R = Me, Et, n-Bu, -(CH2)4-
Nagao, Y. et al, Org. Lett., 6, 2133 (2004)
 Fukuyama Group - Group Meeting Problems
08/04/2004

1 n-Bu
OMe LTMP (2.2 eq)*
N n-BuMgBr (1.0 eq) N N
Cl
Ph THF Ph Ph
–78 °C to rt

84% * theoretical amount: 1 eq

H. Shinokubo, K. Oshima et al., Chem. Lett., 33, 122 (2004)

2 MeS

N 1) Li[Me3AlSPh] 1) m-CPBA
NHFmoc EtOAc, –78 °C, 1 h NH
THF, 36 h
O N
2) piperidine 2) benzene, reflux, 18 h
N CO2Me 3) TFA, CHCl3, reflux, 1 h HN N
THF, 2.5 h
O
71% (2 steps) 70% (3 steps) O

N
H
D. J. Hart, N. A. Magomedov et al., J. Am. Chem. Soc., 123, 5892 (2001)

3 TMS
HO Bu3Sn
SnBu3 (1.3 eq) O
HO HO H
Br Pd(PPh3)4 (20 mol%) TMS

benzene
90 °C, 6 h H

62%
P. Klotz et al., J. Am. Chem. Soc., 123, 12107 (2001)

4
1) On-Bu
1) phenyl thionochloroformate
NO2 DMAP, pyridine N
Me3Al, toluene, –70 °C
MeO2C H H
2) Raney-Ni, H2, MeOH 2) n-Bu3SnH, AIBN, benzene, reflux
3) LiAlH4, THF, reflux H

S. E. Denmark et al., Angew. Chem. Int. Ed., 41, 4122 (2002)

5
O OEt
O
PPh3 (1.2 eq)*
OEt
O AcOEt, 110 °C
(sealed tube) Ph
O
O Ph
72% * theoretical amount: >1.0 eq
M. J. Krische et al., J. Am. Chem. Soc., 126, 4118 (2004)
 Fukuyama Group - Group Meeting Problems
08/11/2004

1
1) TsCN, rt; 3) Br2
AcOH/H2O CH2Cl2, rt Br
63% quant.
BnN
2) KOH; BnBr 4) DBN, 120 °C
DMSO, rt 81% O
71%

TMS Barry B. Snider et al., J. Org. Chem., 50, 1983 (1985)

2 H
1) hν, OTBS 4) TBAF, MeOH-THF, 85%
OTBS benzene, 34% 5) n-Bu3P, CCl4, 92% OAc
Bn O S
S 6) NaI, K2CO3, CH3CN OH H
N 2) DIBAL, MeOH, 0 °C, 60%
Bz O 3) Ac2O, Et3N, THF 70 °C, 72% O
O Ph DMAP, 87%

E. Vedejs et al., J. Am. Chem. Soc., 112, 4351 (1990)

E. Vedejs et al., J. Org. Chem., 69, 5159 (2004)

3 H NC OAc
O CO2Et 1) LDA; MeI
H NaOH THF, –78 °C, 88% Me
CO2Et
H
O EtOH 2) KCN, DMF
O O 40 °C, 98%
65%
3) Ac2O, Py, 85%

B. Zwanenburg et al., Tetrahedron, 47, 1495 (1991)

B. Zwanenburg et al., Tetrahedron, 41, 963 (1985)
4
OMe OMe
1) Cl3CCOCl, Zn(Cu)
MeO Br tol MeO
S THF, 0 °C
2) Al(Hg), THF-MeOH-H2O H
O
O
NaH 3) n-Bu3SnOTf (1.2-1.5) O
CO2Et THF toluene, 50 °C
EtO2C H
CO2Et CO2Et

J. P. Marino et al., J. Am. Chem. Soc., 110, 966 (1988)

5 Ph Ph O O
Cr(CO)5 1% aq. dioxane SET
Ph Ph
OMe 78%
Ph OMe Ph OMe

W. Herndon et al., J. Am. Chem. Soc., 114, 8394 (1992)

 Fukuyama Group - Group Meeting Problems
08/25/2004

1
O O
O Br2; O
KHMDS

72 %

D. F. Taber et al., J. Org. Chem., 64, 9673 (1999)

2
1) aq. HCl, THF
1) aq. HCl 1) ethylene glycol, H+
O (deprotection O
rt, 36 h tetra (protection) O
and ...)
cyclic N
·
Br compound 2) mCPBA 2) aq. NaOH
CN 2) HO
O (epoxidation) MeOH
3) LiBH4
NaH, DMF (opening of epoxide)
3) hν, THF
K. J. Wiesner et al., Tetrahedron Lett., 54, 5643 (1968)
3
O
CHO W(CO)5·THF (10 mol%)
n-butyl vinyl ether

THF H
O
rt
n-Pr H
94%

N. Iwasawa et al., J. Am. Chem. Soc., 123, 5814 (2001)

4
O CONHi-Pr
i-Pr t-BuLi, DMPU, –78 to 20 °C ;
N
hν, –78 °C
Ph Ph
80%, >99% ee

J. Clayden et al., J. Am. Chem. Soc., 125, 9278 (2003)

5
EtO2C CO2Et O
NiCl2(PPh3)2 (5 mol%)
O Zn (1.2 eq), ZnCl2 (1.2 eq)
+
MeCN, reflux CO2Et
CO2Et
58% E:Z= 71:29

K. Odashima et al., J. Am. Chem. Soc., 124, 12060 (2002)

 Fukuyama Group - Group Meeting Problems
09/07/2004

1
1) CO2Me
4) MsCl, pyridine
toluene, reflux 5) DBN H H
2) mCPBA, CH2Cl2 benzene N
N O
CO2Me
3) CO2Me 6) xylene H
O
benzene, reflux reflux H
40% overall yield
J. J. Tufariello et al., J. Am Chem. Soc. 101, 2435 (1979)

2 1) allylboronic acid
HO Cl(CH2)2Cl HO

2) PDC, CH2Cl2
O 3) SmI2, HMPA, t-BuOH, THF Me
HO

Y. Q. Tu. et al., Angew. Chem. Int. Ed., 43, 1704 (2004)

3
MeO O NC Ph
NC
NC OMe
N NC O
O Ph
N toluene
110 °C
MeO2C
CO2Me
81%

J. Warkentin et al., Can. J. Chem., 75, 120 (1997)

4
LHMDS (2.2 eq) ; OH
NHBoc I2 (1.2 eq) Zn(OTf)2 (0.1 eq) LiOH (2.0 eq)
CO2H
CO2Me Ph
Ph THF CH2Cl2 H2O
NH2
85 % 98 % 90 %

C. Tomasin et al., Org. Lett., 1, 2153 (1999)

5 O
Et3N Li
Cl A
PhMe THF
reflux C11H14O –78 °C O
then
rt

Snider, B. B. J. Org. Chem., 53, 4508 (1988)

 Fukuyama Group - Group Meeting Problems
09/29/2004

1 1) NaH, DMPU, THF;

propargyl bromide
2) TsOH HO
BuLi, THF, –78 °C; acetone-H2O Me

O O
3) SmI2, HMPA
CHO t-BuOH-THF O
(1:1 mixture)
J. D. Kilburn et al. J. Chem. Soc., Chem. Commun., 1875 (1998)

2 1) t-BuOK (2 eq);
2) p-TsOH
H
benzene, reflux
I O2 72%
PPh3 dimeric
compound
I benzene, 50 °C 3) CO2Et CO2Et
67% H CO 2Et
CO2Et
EtAlCl2
CH2Cl2, rt
42%
L. Fitjer et al. Tetrahedron, 54, 10713 (1998)

3
2) Tf2O (1.1 eq) OH
1) CuBr2 (2.0 eq) t-Bu N t-Bu 3)
O CHCl3-EtOAc (2 eq*)
reflux, 12 h; cat. PdCl2(PPh3)2 CHO
filtration; Me (1 eq) Hünig base (3 eq)

NHSO2Ph Et3N (1.0 eq) CH2Cl2 DMF N

SO2Ph
0 °C, 2 h 0 °C, 1 h; 80 °C, 24 h
70% rt, 3 h 82%
84% * theoretical amount: 1 eq
G. W. Gribble et al., Synth. Commum., 22, 2129 (1992)

4 MeO
Bubbling O2 MeO
TPP (sensitizer) (0.05 eq)
hν (300W)
O CHO
O
N CH2Cl2 O N Me
Me 40 °C, 90 min
MeO 62% CHO
TPP = meso-tetraphenylporphyrin O

R. Riguera et al. J. Org. Chem., 65, 4671 (2000)

5 STr
O Ph3P=O (3 eq.) S
OMe Tf2O (1.5 eq.) Ph
N CH2Cl2, 0˚C N COOMe
H
O 10 min
98%

S. L. You et al, Angew. Chem. In. Ed., 42, 83 (2003)

 Fukuyama Group - Group Meeting Problems
10/06/2004

1
Ti(O-i-Pr)4 (1.5 eq) O Et

Ac CyMgCl (4.4eq) (n-PrCO)2O KOH OH

N
Ph THF PhCl Ac2O MeOH
10 min reflux, 3.5 h reflux, 50 min reflux, 6.5 h
Ph N
90% 50% 69% 75%

Y. Six et al., Eur. J. Org. Chem., 3517 (2004)

2
O
S Me3OBF4;
N2 Rh2(OAc)4 Raney Ni NaBH4 TEOC-Cl*
N
benzene acetone benzene
65% (2 steps) rt N
O reflux
30% (3 steps) TEOC

*TEOC-Cl= 2-(trimethylsilyl)ethyl chloroformate

S. J. Danishefsky et al. J. Am. Chem. Soc., 112, 2003 (1990)

3
BnBr, TBAI OHC
O NaH t-BuLi
TMS
THF, 0 °C to rt THF-HMPA BnO TMS
OH
78% 40%

M. E. Jung et al., J. Org. Chem. , 61, 9065 (1996)

4
1) propionyl chloride O
CH2Cl2, rt; 3) t-BuOK, THF, 0 °C N
O AgOTf, –20 °C 4) Lawesson's rgt, THF, rt O
O NC 2) Br(CH2)3COCl 5) P(OMe)3, reflux S
CH2Cl2, 0 °C;
sat. NaHCO3 aq O

S. J. Danishefsky et al., J. Org. Chem. , 55, 831 (1990)

O
MeO OMe
OH
malonic acid (cat.)
200 °C, 48 h
73%

I. Farris et al., Helv. Chim. Acta., 87, 1601(2004)

 Fukuyama Group - Group Meeting Problems
10/13/2004

1 N N
O N O
MeLi, MeOMe 1) aq. KOH, MeOH
Ph
– 45 ºC; 1 day; reflux

MeLi, CH2Cl2 Et2O/dioxane 2) CuCl2, aq. HCl, rt; toluene, 40 ºC

Me2O, Et2O NaOH, 0 ºC 1d
– 45 ºC 1 h, rt 65% (2 steps)
10%
29% 60%
T. J. Katz et al., J. Am. Chem. Soc., 93, 3782 (1971)
T. J. Katz et al., J. Am. Chem. Soc., 95, 2738 (1973)
2

1) benzene MeO2C
Ph
N3 reflux
N
Ph MeO2C
N O 2) hν N
CO2Me MeOH

A. G. Schultz et al., J. Org. Chem., 45, 2040 (1980)

3
1) LHMDS;
TBSO H acrolein 3) Cl2
TBSO H H
SPh THF, –78 °C CH2Cl2, –78 °C
91% 85%
CHO
N N
O CO2Me 2) TBSOTf, lutidine 4) AgBF4 O
CH2Cl2 CH2Cl2, –78 °C CO2Me
88% 33%

H. Horikawa et al., J.C.S. Chem.Com., 2527 (1995)

4

1) n-BuLi, TsCl H
Bu3SnH, AIBN O
2) PhSLi

3) MCPBA toluene, 110 °C

80% (3 steps) H
OH 46%

S. Itoh et al., Angew. Chem. Int. Ed., 41, 4325 (2002)

5

CO2Me
(CH2=O)n (5 eq.), CO2Me (4 eq.)
PhMe, 100 °C, 4 h;
CO2H N
N Bu2SnCl2 (0.1 eq.)
H
78%
MeO2C

H. Ardill et al., Tetrahedron, 50, 5067 (1994)

 Fukuyama Group - Group Meeting Problems
10/20/2004

1
1) MeOH, reflux
2) TsCl, Py 1) KOH
C11H16O2 C11H16O
3) NaOMe 2) MeLi (2 eq) 210 °C
OTMS O
MeOH 85%
OTMS

X. Creary et al., J. Org. Chem., 42, 409 (1977)

2 Cp2ZrCl2 (1 eq)
n-BuLi (2 eq)
OTMS O
THF, –78 ºC to rt;

Ph N Ph N Ph
n-BuLi (1 eq) –78 ºC; H
PhCHO, rt
50%

V. Gandon et al., Tetrahedron, 56, 4467 (2000)

1) Pd(dba)2 (5 mol%) 1) MeNHOH·HCl, Et3N N O

H
dppe (7 mol%), THF; toluene, reflux, 90%
C18H16N2O5S
OTs CO2Et H
2) TFA, reflux, 72%
N
, NaH, 98%
NHNs Ns
2) DIBALH, CH2Cl2, 86%
3) DMSO, (COCl)2, CH2Cl2;
Et3N, 81%
F. M. Cordero et al., J. Org. Chem., 68, 3271 (2003)

1) acryloyl chloride
1) PhOCOCl toluene, 75 °C
N N
ClCH2CH2Cl CN 2) 2-mercaptopyridine- CN
reflux, 66% N-oxide, Et3N, CH2Cl2; MeO
N
N
H 2) Tf2O, DMAP N hυ, t-BuSH, N
MeO2C CH2Cl2, reflux; H 39% (2 steps) H
TMSCN CO2Me 3) PhI(OAc) , MeOH; CO2Me
2
68% Zn powder

P. Magnus et al., Tetrahedron, 58, 3423 (2002)

5
H Zn(N3)2·2Pyr Me
OTIPS H H
DEAD, PPh3 TfOH OTIPS
PhCH3 CH2Cl2
N
O H Me (50%) (52%) H Me
O
OH

J. Aube et al., J. Am. Chem. Soc., 126, 5475 (2004)

 Fukuyama Group - Group Meeting Problems
11/02/2004
1) Cu(acac)2, toluene
1 85 °C, 58%
HO
H
OH
SiPhMe2 2) L-selectride, <88%
N
3) Hg(O2CCF3)2 N
N2
AcOH, TFA, CHCl3;
O AcOOH, 81%
85% ee * Product of 1) was found to be 77% ee.
F. G. West et al. Org. Lett., 4, 2813 (2002)

2 I S
N OH
Me

tol PhCHO
SO2 Ph NHBoc
Et3N
Ph NHBoc CH2Cl2 Ph O
35 °C
75% P. J. Reider et al., Chemtracts 16, 579 (2003)

3
O
Me NH
Me OAc
1) ClCOCH2SEt (1.1 eq) Ac2O (10 eq) N
O
benzene, reflux p-TsOH
98%
xylene
N 2) NaIO4 (1.1 eq) reflux
MeOH-H2O 64% N
O 96%
Ph O
Ph
A. Padwa et al., J. Org. Chem. 65, 2368 (2000)

4
Ph
N OTBS
N O O
O Ph3SnH
O cat. AIBN
O O O
O TBSO PhH, heat NHOBn
I NOBn
O
O
G. E. Keck et al., J. Org. Chem. 63, 9164 (1998)

5
1) (COCl)2, CH2Cl2; SnCl4 [Ph3P+CH3]Br- O
OH 53% NaH TsOH·H2O MeO
O O THF MeOH-H2O
O
2) CHN2 ,Rh(OAc)2
85% 99%
benzene
80%
A. Padwa et al., J. Org. Chem., 61, 73 (1996)
 Fukuyama Group - Group Meeting Problems
11/09/2004
Cl
1 EtO2C NHBz
Cl 1) P(OEt)3, reflux
4 h, 68% OH
O O N
2) K2CO3, CH3CN CO2Et
NO2 reflux, 3 h, 80% O
BzHN

M. L. Gelmi et al., J. Chem. Soc. Perkin Trans. 1, 969 (1993)

2 H CH2OAc H CH2OAc
OBz OBz

O CrO3 (3 eq) H O
H
Bu4NIO4 (3 eq) OH
H H H H
AcO –40 °C, 10 min AcO
H 97% H
P. L. Fuchs, Org. Lett., 6, 1437 (2004)

3
O BrMg (1.1 eq) HCO2H (xs)

THF toluene NH
N rt, 2 h reflux, 30 min O
Br Br
80% 65%

W. W. McWhorter, Jr., et al., Org. Lett., 5, 333 (2003)

4
O 1) cyclopentadiene
Et3N t-BuLi, Ti(OiPr)4 O
Cl
2) NBS, hν –80 °C
CCl4, 80 °C

R. Sigrist et al., J. Chem. Soc. Chem. Commun., 944 (1986)

5 OMe
OMe
MeO
MeO 1) (CH2OH)2, p-TsOH(cat.), toluene, reflux, 77 %
2) LiAlH4, THF, reflux, 95 %
CO2Me 3) PhSO2Cl, Et3N, CH2Cl2, 0 °C - rt, 82 %
O NMe
NH 4) Li, NH3, tBuOH, THF, —78 °C, 76 %
O HH
OMOM
O

K. Ogasawara et al., Org. Lett., 4, 4515 (2002)

 Fukuyama Group - Group Meeting Problems
11/16/2004

1
1) Rh(acac)(CO)2 (3 mol%)
CO (1000 psi) OH OH OH
Si PhH, 60 °C
O H
2) H2O2, NaHCO3
THF/MeOH, Δ 65% dr = 93:7

J. L. Leighton et al., Tetrahedron, 59, 8889 (2003)

2
OCO2Me (2.0 eq)

TMS TMSN3 (2.0 eq)

Pd2(dba)3• CHCl3 (2.5 mol%)
P(2-furyl)3 (10 mol%) MeMgBr (4.0 eq)

NC toluene THF N TMS

100 °C, 1 h 0 °C to rt, 4 h H

59% 93%
Y. Yamamoto et al., J. Am. Chem. Soc., 124, 11940 (2002)

3 aq. NaOH
cat. BnEt3NCl
Cl Cl NaH, CS2 Cl OPh mCPBA (1 eq) Cl S S

DMF-benzene; CHCl3 CHCl3 CCl4

115 °C 0-5 °C reflux OPh
O 82% O
O
63% 70% (2 steps)

K. C. Majumdar et al., Synth. Commun., 34, 2159 (2004)

4 Me O
N 1) NaH, benzene, 100 °C
N Me 2) KOH, 75% (2 steps) N
N
3) (CH2O)n, MeCN, 80 °C
O 4) LDA, NCCO2Me, –78 °C N
5) 10% HCl-MeOH, 70% (3 steps) H OH
CO2Me

F3COCHN Ot-Bu
L. E. Overman et al., J. Am. Chem. Soc., 117, 5776 (1995)

5
OH
1) I2, Na2CO3•5H2O
Na2CO3, Et3N CH2Cl2
CF3CF2 CO2Et O
O
Et2O, 3 days 2) DBU, PhH CO2Et
reflux, 1 hr CF3

C.-M. Hu et al., J. Org. Chem., 62, 4147 (1997)

J.-P. Bégué et al., J. Chem. Soc. Perkin Trans 1, 2787 (1993)
 Fukuyama Group - Group Meeting Problems
11/24/2004

1
hν

100 ºC, 5 d Et2O

rt, 1 d
20-25%
20% overall

Schroder, G. et al., Angew. Chem. Int. Ed., 2, 481 (1963)

J. F. M. Oth et al., Angew. Chem. Int. Ed., 6, 414(1967)

2
1) O3, CH2Cl2, – 78 °C; Me2S, 85%
1) acrolein, rt 2) LiEt3BH, THF, 0 °C, 85%
O
O
2) hv, Et2O, 31% 3) Li, ethylenediamine, 37%
+ regioisomer, 26%
4) (COCl)2, DMSO, CH2Cl2,
– 50 to – 60 °C; Et3N, – 50 to – 60°C
80%

R. Gleiter, Eur. J. Org. Chem., 171 (1998)

3 S O
1) H2N NH2 , DMSO;
O Br aq. NaOH 3) 40% AcOOH, quant. O CO2Me
O Br 2) NaOH, THF, rt; 4) methyl acrylate,
n-BuLi, –78 °C; di-n-butyl phthalate
3,4-dimethoxybenzaldehyde; 200 °C, 75% OMe
conc. HCl, 40%
OMe

J. Mann et al., J. Chem. Soc., Chem. Commun., 430 (1982)

4
3) H2/Pt
O (reduction of H
O 1) HCl, AcOH hemiaminal)
O NHCOCF3
2) K2CO3 4) LAH N
O aq. MeOH, 50 °C THF
82% 52% (2 steps)

Y. Ban et al., Tetrahedron. Lett., 4249 (1983)

5
Bu3Sn SnBu3 PhI(CN)OTf Bu3Sn SnBu3
CH2Cl2;
concentrated at –40 °C;
N
N
TolSO2Na
O
DME, reflux O
SnBu3 Ts

K. S. Feldman et al., J. Org. Chem., 69, 7928 (2004)

 Fukuyama Group - Group Meeting Problems
12/07/2004

1 O

N
N LiClO4
PhSOCH2Cl Me
POBu3 LAH OH
+ N
THF toluene Et2O N
LDA -78 °C; reflux Me
KOH

J. M. Cook et al., J. Am. Chem. Soc., 111, 7505 (1989)

2
1) PPh3, THF, reflux, 54% 4-ClC6H4CHO PMP
O 2) 180-190 °C, 98% BF3·OEt2
Br C18H18O2
3) n-BuLi, THF; CH2Cl2 MeO OH
O 4,4'-dimethoxybenzo- 4-ClC6H4
phenone, reflux, 28% 95%

M. Shi et al., Org. Lett., 6, 1175 (2004)

3
1) Ethyl pyruvate (4 eq) O
OH p-ClPhSH (4 eq) O
Ph Et3N, AcOH, EtOH
Ph
sealed tube
N O 110 °C, 3 d, 72%
H N O
2) 2% TFA/toluene H
reflux, 12 h, 93%

B. B. Snider et al., Org. Lett., 6, 2877 (2004)

4
O CO2H 1) Ac2O,Py O
CO2Bn 90 ºC, 94%
N CO2Bn
H N
2) POCl3, DMF
MeO 90 ºC, 84% MeO

A. G. Godfrey et al., J. Org. Chem., 68, 2623 (2003)

5 Br CHO
O SmI2; OH OH
Br Br
OTIPS K2CO3 OTIPS
Formate
; CH3CHO MeOH
(96% , single diastereomer)

John L Wood et al., Org. lett., 4, 3087 (2002)

 Fukuyama Group - Group Meeting Problems
12/15/2004
Ph
1 OH Aqueous glutaraldehyde (2.5 eq.) 1) LiAlH4, Et2O, 82%
OH
NH2 C26H31NO4S HN
pH=3.5, NaSO2Tol (2.2 eq.) 2) Na(Hg), 95%
(R)-(–) phenylglycinol ZnBr2, 3 h, 51% 3) H2/Pd/C, 85%
(+)-Isonitramine

H.-P. Husson et al., Angew. Chem. Int. Ed., 37,104(1998)

OMe
2
R=Me

OR 68%
cat. PtCl2

toluene OAc
80°C OAc
+
R=Ac

88% 5-10%
M. Malacria et al., Angew. Chem. Int. Ed.. 41, 2132 (2002)

3 Ms Ms

1) t-BuOK, THF; Cl
POCl3 A
O A
Cl DMF (C7H14N2ClPF6) O N
OH 2) AcOH/TFA
75 °C; 3) NH4OH, reflux
N Me N Me
60% aq HPF6
NaOH Etoricoxib

I. W. Davies et al., J. Org. Chem., 65, 8415 (2000)

4 O SMe
MeS
SMe
MeMgI SnCl4
MeS
H
Et2O CH3NO2

78%
MeO MeO

P. K. Bharadwaj et al., J. Chem. Soc., Perkin Trans. 1, 1547 (2000)

5 LDA
i-Pr THF OMe
N 0 ºC, 1.5 h; K2CO3 O

Br(CH2)3OSiMe3 MeOH
Cl rt, 18 h Δ, 1h NH(i-Pr)
62% 80%

W. Aelterman et al., Tetrahedron Lett., 45, 441 (2004)

 Fukuyama Group - Group Meeting Problems
01/11/2005
1
N
H Me
2N HCl
N C19H24N2O2
H H
O reflux, 24 h
H
MeO2C
1) PTSA(1.1 eq), dioxane, reflux, 45 min, 77%(2 steps) HO
O
2) Boc2O, DMAP(cat.)CH2Cl2, rt, 4 h, 84%
N
3) mCPBA(1.3 eq), CH2Cl2, 0 °C, 1 h, 94% N
4) TFAA, CH2Cl2, rt, 3 h; KCN/H2O(pH=4), 0 °C, 30 min; Boc H
H OH
rt, 3 h, 25%

H.-P. Husson et al., Tetrahedron Lett., 42, 3291 (2001)

2
N P(O)Cl3 H
N
N
H Et (neat) H
N rt, 6 h
H 55% Et
NOH CN

par G. Hugel et al. Tetrahedron Lett., 17, 1597 (1974)

3 3)
O MgBr
1) CH2N2
CO2Et Pd(OAc)2 (cat) THF, 0 °C O
Et2O/H2O, 47% 82%

2) MeNH(OMe)·HCl 4) Cr(CO)5(thf)
TMS AlMe3, THF, 99% Et3N, THF OH
69%

S. Uemura et al., J. Am. Chem. Soc., 124, 526 (2002)

4
S 1) COCl2 S
CH2Cl2-toluene PhCOSH
MeO2C MeO2C
NMePh NMePh
2) DABCO, THF CH2Cl2 BzHN
3) NaN3, DMF 99%
90% (3 steps)

H. Heimgartner et al. Helv. Chim. Acta, 87, 2539 (2004)

5 MeOOC H
MeOOC hv, Corex N COOMe
N N
cyclohexane
MeOOC +

MeOOC H
COOMe
major minor

J. D. White et al J. Org. Chem., 69, 3758(2004)

 Fukuyama Group - Group Meeting Problems
01/19/2005
1

1) DBU, t-BuOH, Δ
N 2) decaline, Δ
+
S 3) MeI; K2CO3, EtOH
Br
CO2Et

Z. Yoshida et al., J. Am. Chem. Soc., 102, 2392 (1980)

2 CN

Cl O O
OMe
OMe LDA Me

THF
– 40 °C to rt, 2 h
Me OMe O OMe
40%

E. R. Biehl et al., J. Org. Chem., 52 , 5685 (1987)

3
O
O Me Me
Me Me
Me EtAlCl2 H
Me
toluene, 0 °C to rt Me
Me
80% Me

A. Goeke et al., Angew. Chem. Int. Ed., 44, 99 (2005)

4
1) CH2ICl, MeLi, THF 3) NaBH4, MeOH Bn NHBn
Bn CO2Et –78 °C, 85% rt, 92%
C31H31ClN2 N N Bn
NBn2 2) BnNH2, TiCl4, Et2O 4) BF3•OEt2, i-PrCN*
0 °C to rt, 74% reflux, 61% iPr

* theoretical amount: 2.0eq

J. M. Concellón et al., Org. Lett., 6, 4499 (2004)

J. M. Concellón et al., J. Org. Chem., 66, 2764 (2001)
5
O
O
EtO
LDA, THF, –80 °C; 1) t-BuLi, CH2Cl2 EtO2C
–115 to –45 °C O O
Br
Br O 2) aq. HCl, CH2Cl2
EtO2C O 59% (2 steps)
O 3) O3, MeOH, –80 °C; O
Me2S, rt, 81%
–80 °C to rt

51% D. Spitzner et al., Tetrahedron, 60, 8137 (2004)

 Keys to the Problems (01/11/2005)

1
N N N
H Me H Me H Me
N N N
H H H H H H
H O H2O H O H O
MeO MeO HO
O O H O H OH2
H OH2

N N N
H Me H Me H Me
N N N
H H H H H OH2 H H
H O H O H OH
HO HO O
OH2 OH O
O O O H

N N N
–CO2 H Me H Me H Me
N N N OH
H H OH H H H H H OTs
H H H O H O
H OH2
O OH C19H24N2O2
H OH2

N N N
HMe H Me Me
N OH2 N N
H H H H H H
O O tBuO O OtBu H O
H H
1)
O O

O
O
HO Cl F3C OCOCF3 O CF3
O
O O
N N N
Me Me Me
N N N
Boc H Boc H Boc H
H O H O H O
3)
2)

O CF3 CF3
O
O OH2
O OH
N N N
Me Me Me
N N N
Boc H Boc H Boc H
H O H O H O
O
O
O OH
4)
O CF3 H2O CF3

Fukuyama Group - Group Meeting Problems

 Keys to the Problems (01/11/2005)

2 N N N

H Et H Et H Et
N N N NC
H H abnormal Beckmann H
N O N rearrangement
OH OP(O)Cl2
P
Cl Cl
Cl

N H H
N N
N N
H H H
Et
N NC Et Et
H CN CN

3 OEt
MeNHOMe
AlMe3
O O
–Pd0
TMS
CH2Cl2 + Pd(OAc)2 Pd CH2 Pd OEt OEt CH4
Me OMe
N
TMS TMS AlMe2
1)

O O O
O BrMg O O MgBr workup Cr(CO)5(thf)
OMe O
N N O O
Me Me
Me
Cr(CO)5
TMS TMS H
H
Weinreb's amide 2) 3)

O O O O

O O O O
Cr(CO)5
H Cr(CO)5 Cr(CO)5
H

O
O workup
OH
O
O CrLn
OCrLn 4)
H

Fukuyama Group - Group Meeting Problems

 Keys to the Problems (01/11/2005)

O
O
4
Cl S Cl Cl Cl
Cl Cl
S MeO2C Ph MeO2C Ph
N N
MeO2C Ph H
N
N 1)
N

N2
Cl N3 N
N
MeO2C Ph MeO2C Ph MeO2C Ph
N N

2)

S Ph
H
N N HN
MeO2C Ph MeO2C Ph MeO2C Ph
N N N
3)

O
Ph
S Ph O S
HN S
MeO2C Ph MeO2C Ph
N HN N
Ph
N HN
O
MeO2C Ph

MeO2C MeO2C MeO2C

5 N
hυ
N N H
CO2Me
N
MeO2C MeO2C MeO2C
H
CO2Me

MeO2C MeO2C MeO2C MeO2C

N N N N
or, hυ
MeO MeO MeO MeO

O O O O

H H
CO2Me CO2Me
N N

H
CO2Me CO2Me

Fukuyama Group - Group Meeting Problems

 Fukuyama Group - Group Meeting Problems
02/01/2005
1
1) MT-sulfone
Bu3P CHCN 3) AgNO3
benzene, 120 °C MeCN/H2O OH
72% 81%

OH 2) SO2Cl2 4) LAH
CHCl3, reflux THF, 0 °C
99%
T. Tsunoda et al., Tetrahedron Lett., 36,2531 (1995)
2 NH2
Me Me
NH2 N

PhMe, reflux
O 4 days N
Me Me
68% Me H

A.Hakiki et al., Tetrahedron, 51 , 2293 (1995)

3 O
1) hν, CF3CH2OH
2) H2, Pd-C 1) TsCl, Py (1 eq)
O
OH O
3) NaBH4, EtOH 2) MeS(O)CH2–Na+ (as base, 1 eq))
75% (3 steps) DMSO
78% (2 steps)

4 F. G. West et al., J. Org. Chem., 63, 2806 (1998)

O
1) (BzO)2, cat. HCl(g)
CH2Cl2; S H
O (EtO)3P, xylene CO2Me
HN 85 % as diasteromers N
O H + H A
CO2Me O
2) P2S5 HN H
HN CO2Me 4-methoxypyridine
S xylene S
6 h, 120 °C CO2Me
84 % as diasteromers
O

S H CO2Me
MeO2C H t-BuOK
N t-BuOH, THF; N
A+
Br P(CH2CH2CN)3 MeO2C H N HN H
TFA, sulfolane
60 °C
NC NC CO2Me
64 % as diasteromer

Eschenmoser, A. et al., Science, 196, 1410 (1977)

5 1) NH2NHCOOEt
cat. AcOH
MeOH, reflux, 1hr 3) PhLi/THF
80% –60°C, 30min
N N SMe
O 2) SOCl2 ;Me2SO2 –60 to 0 °C
0 to 60°C 82%
88%

K. Pacaud et al., Bioorganic Chem., 60, 8137 (2004)

 Fukuyama Group - Group Meeting Problems
02/16/2005
1
O PhSe SePh O
s-BuLi TlOEt

Et2O CHCl3
–78 ºC reflux
67% quant

Paquette, L. A. et al., J. Org. Chem., 50, 5200 (1985)

2 H
1) Me3NO, acetone
MeI, THF; reflux, 63% H
Fe(CO)3 OH H
Me2N 2) MesN NMes
O
Cl
Ru
Cl Ph
NaH, THF-DMF PCy3
0 to 80 °C , ethylene
benzene, 50 °C;
50% reflux, 74%
Snapper, M. L. et al., J. Am. Chem. Soc., 122, 8071 (2000)
3
t-Bu
Si
O t-Bu OH
O AgOCOCF3 (1 mol%) 1) LAH, THF, reflux
silalactone
toluene 2) KH, Ph(CH3)2COOH
rt CsF, NMP-THF, rt OH
95% 87% (2 steps)

Woerpel, K. A. et al., J. Am. Chem. Soc., 127, 2046 (2005)

4
1) p-MeC6H4SSCl
CH2Cl2, 0 °C tricyclic compound hν
C7H8S S
2) Na2S MeCN
C7H8

T. Fujisawa et al., J. Chem. Soc., Chem. Commun., 1298 (1972)

5
1) SOCl2
O Allylamine
O Et3N, benzene CN
hν quant.
C10H12O2
Cl acetone-H2O 2) Ph3P, MeCN
6h CCl4, Et3N
(C10H11ClO) 70% 24 h, 80%

S. P. Chavan et al., Tetrahedron. Lett., 37, 2629 (1996)

 Fukuyama Group - Group Meeting Problems
02/23/2005
1 CH3 3) MsCl, Et3N
5)
1) n-BuLi E
H Et2O, 0 °C
H E
2) (CH2O)n Pd(OAc)2
H 4) E
THF, –78 °C PPh3, K2CO3
88% E Br DMF, 110 °C, 12 h H3C
14%
NaH, THF, 25 °C
69% (E=CO2Me)
de Meijere, A. et al., Eur. J. Org. Chem., 582 (2005)

2
N2
EtO2C
CO2Et
NHBoc Rh2(OAc)4 NaH NBoc

N S Me CH2Cl2 THF
H N S Me

Rainier, J. D. et al., J. Org. Chem., 70, 746 (2005)

3 O
H P(OMe)2 (4 eq)* Me2N
NO2 Me2NH (4 eq)**
MeONa (3 eq) Adirine- N
Containing P(O)(OMe)2
MeOH Intermediate
5-10 °C
89%
* theoretical amount ··· 2 eq
** theoretical amount ··· 1 eq Makosza, M. et al., J. Org. Chem. 56, 1283 (1991)

4 OH 1) TMSCl, DMAP
OHC-CHO NEt3
bicyclic compound THF, rt Ph
Ph NH
H2O-THF C15H19NO3 O
2) Ph3P=CH2 Cl N
95%
THF, 0 ºC TMSO
HO Me O O
3) CH2=CH-OCOCl
CH2Cl2, reflux

Agami, C. et al., Tetrahedron 49, 7239 (1993)

5 O
N O
HC CCO2Et
S O N
N NaH Na
N
THF p-xylene
rt, 30 min reflux, 2 h;
AcOH
57%
93%

Kim, K. et al., Heterocycles 57, 2267 (2002)

 Fukuyama Group - Group Meeting Problems
03/02/2005
1
O
1) BrCCl3, DBU, CCl4, hν, 85%
OEt 2) nBuCu(CN)Li, THF, –30 °C; AcOH-THF, 80%
TBSO
TBS 3) LDA, 1-acetylcyclopentene, THF, –80 °C to 0 °C, 48%
nBu

Takeda, K. et al., Org, Lett., 1, 677 (1999)

2
BnN t-BuOK NBn
O2, P(OEt)3 silica gel O
H
t-BuOH-monoglyme HO
NH2
O O –20 °C; 96% O NH2

Büchi, G. et al., J. Am. Chem. Soc., 92, 999 (1970)

3
O PhCH2CN (1 eq)
H PCl5 (2 eq) NaH (3 eq) N
N
N
H toluene THF N
O reflux, 4 h reflux, 12 h H
63% 83% Ph

Langer, P. et al., Eur. J. Org. Chem., 5020 (2004)

4
DMAP (5 mol%)
O HOCH2CH2OH
O O O
OMe
0 °C to rt, 24 h H OMe
81%

Connon, S. T. et al., Chem. Comm., 227 (2005)

5
aq. CH2O
PhSH TMSCH2OTf O
O
Et3N CH3CN;
C12H12OS
EtOH CsF
reflux 54% SPh
73% 1H-NMR: δ 7.17-7.51 (m, 6H),
3.68 (d, 2H), 2.42-2.56 (m, 4H)

Cohen, T. et al., J. Org. Chem., 50, 2965 (1985)

 Fukuyama Group - Group Meeting Problems
03/08/2005
1
(thf)W(CO)5
(25 mol%) HCl
O
OH THF, rt acetone, rt HO
90% 98%

Barluenga, J. et. al., Angew. Chem. Int. Ed., 44, 126 (2005)
2
MeO OMe
1) propargyl bromide
N K2CO3, LiBr, nBu4N+Br-
DMF PhMe/H2O aniline
OMe
80 °C, 3 h; 100 °C, 1 h Dy(OTf)3 (10 mol%) O
MeO N
cyanoacetamide 2) AcOH/HCl/H2O MeCN N
O CN
DMF 60 °C, 1 h 50 °C, 16 h
100 °C, 3 h
86% (2 steps)
71%
29%
Batey, R. A. et al., Org, Lett., 6, 4913 (2004)

3 1) 160 °C
O 2) LDA (1.1 eq), THF;
ClCO2Et (1.1 eq)
O PPh3 A
Br 3) NaBF4
(counter anion exchange)
CO2Et
H
O O
NaH; A
O

Dauben, W. G. et al., J. Am. Chem. Soc., 99, 7307 (1977)

4
O O
H 1) TsCl, Et3N, CH2Cl2, 83%
N CO2Me 2) 4-ethyl-4-pentenoic acid N
N N WSCD•HCl, DMAP, CH2Cl2, 87%
H H
O
3) o-dichlorobenzene O
N 180-190 °C, 74% N
Me Me CO2Me

Boger, D. L. et al., Org. Lett., 7, 741 (2005)

5
1) Tf2O, DTBMP*
CH2Cl2, 95% 1) Tf2O
2) LAH, Et2O CH2Cl2
0 °C, 64% 0 °C

O 3) mCPBA 2) CH3CN, reflux; O

CH2Cl2, 78% sat. NaHCO3, 85% AcHN

*2,6-di-t-butyl-4-methylpyridine
Maritinez, A. G. et al., J. Org. Chem., 68, 1451 (2003)
Maritinez, A. G. et al., Tetrahedron, 61, 599 (2005)
 Fukuyama Group - Group Meeting Problems
03/16/2005
1 1) NO2
2) Pb(OAc)4
Ph
N O2N ONH2 O
N
O N O O
N 48% –50 °C, CH2Cl2
H
57%

Murata, I. et. al., Tetrahedron Lett., 35, 8421 (1994)

2 O
O
N2 O
Rh(OAc)2
MeO2C
DMAD MeO2C
N
H
O 70% N

Padwa, A. et al., J. Org. Chem., 60, 53 (1995)

3
O

O Ox O
O
O
OH PhMe, reflux O Ox =
Ox N
90%

P. A. Jacobi et al., Tetrahedron Lett., 29, 6865 (1988)

4
CO2Me 1) N2H4 (2 eq)
EtOH 1) MeI, aq. NaOH C8H8 hν, Me2CO
1H NMR:
2) NaNO2, HCl; 2) Ag(OH)2, H2O 4.60(m, 2H)
Δ, 16 h 50 ºC, 0.5 h 6.63(sextet, 6H)
69% (3 steps) semibullvalene
CO2Me

Zimmerman, H. E. et al., J. Am. Chem. Soc., 91, 2330 (1969)

Zimmerman, H. E. et al., J. Am. Chem. Soc., 91, 3316 (1969)

5
1) TosMIC (1 eq)
NHAc
K2CO3 (1 eq) MeO
MeO MeOH, reflux, 1 h NHAc
CHO
2) KOH (xs) o-dichlorobenzene MeO
MeO reflux, 40 h OMe O
MeOH, reflux, 3 h
OMe H 64% (2 steps) 70%

J. K. Cha et al., Tetrahedron, 56, 10175 (2000)

 Fukuyama Group - Group Meeting Problems
03/23/2005

1
Cl CO2Et

CO2Et
BuLi DBU CO2Et
SO2Ph
THF benzene CO2Et
–78 °C to rt reflux

83% 92%
S. Koo et al. Tetrahedron Lett. 45, 7023 (2004)

aq. HCl
2
THF, reflux
Me O
O 72% Ph
PtCl2 (5 mol%) tricyclo compound
Ph (except for Ph group)
toluene, 80 °C
O H
84% DDQ (2 eq)
O
CH2Cl2-H2O, 40 °C O O

60% Ph
A. M. Echavarren et al. Org. Lett. 6, 3191 (2004)
3
cat. [RhCl(CO)dppp]2 SO2Ph
1) PhSCl, Et3N
TMS THF, –78 ºC CO (1 atm)
HO O
2) m-CPBA toluene
CH2Cl2, 0 ºC reflux
TMS
85% (2 steps) 97%

C. Murai et al. J. Org. Chem. 68, 1376 (2003)

4
TBSOTf
Rh2(OOct)4 Et3N
N2 O
CH2Cl2 CH2Cl2 toluene O
O 65 °C OTBS
20%
O O 55%
(2 steps)

H. M. L. Davies et al. J. Org. Chem. 65, 4261 (2000)

5
O O Rh2(OAc)4
O BF3·OEt2 O O
HO
OMe
PhH, 80°C PhH OMe
N2 OMe
OH HO
O

John L Wood et al., J. Am. Chem. Soc., 117, 10413 (1995)

 Fukuyama Group - Group Meeting Problems
04/06/2005

1 1) Bu3SnH (1.2 eq)

O Br AIBN (cat) OH Me
PhH, 80 °C
Me3Si
2) TBAF, THF
H
81% (2 steps)

Tsai, Y. M. et al., Tetrahedron Lett. 34, 1303 (1993)

O 1) Rh2(OAc)4 (3 mol%), CH2Cl2, 74% Me

2) 6 N HCl, 1,4-dioxane, 93% O H
O O
3) MeI, NaH, DMF, 75%
N2 4) sealed tube
O 1-methylcyclohexene, 150 °C, 62%
OMe
O

J. E. Baldwin et al. Org. Lett. 1, 1933 (1999)

3

Me H2N OMe
O NO2 Boc2O Raney Ni O
Me DMAP H2
OMe tricyclo compound O
Me
Me benzene-MeCN MeOH
Me Me Me
Me

D. G. J. Young et al. J. Org. Chem. 67, 3134 (2002)

4
AcO S CO2CH3
S
K2CO3 TsOH·H2O CO2CH3
N Et N
MeOH-H2O toluene
reflux Et
O Me
76%

H.-G. Hahn et al. Heterocycles, 57, 1697 (2002)

5
Ph
O Ph
O O O
O OTMS SO2, toluene "H+" ∗
∗ ∗
C29H40O6SSi O Ph
Ph O Tf2NH (cat.)
78% d.r. 5:1
C26H32O4
C21H22O3 C8H18OSi
Stereochemistry C*?

P. Vogel et al., Chem. Eur. J.,11,465 (2005)

 Fukuyama Group - Group Meeting Problems
04/12/2005

1
1) SeO2
TBHP
CH2Cl2 3) DBU (2.0 eq) HO
OH
O
2) AllylBr toluene
NaH 220 ºC
THF µwave
75%

L. Barriault etal., Org. Lett. 4, 1371 (2002)

2
N3

Me toluene, 100 °C; NH

H CN
TMSCN
Ph Me
Ph
K. S. Feldman et al., J. Am. Chem. Soc., 127, 4590 (2005)

3 1) TrisNHNH2, THF;
t-BuLi (theoretically 2 eq),–78 °C;
t-BuO O
Ot-Bu
O , 36%
O O H
H
2) µwave, THF, 110°C; air, 80%
3) µwave, toluene, 150 °C, 61% O

D. C. Harrowven et al., Angew. Chem. Int. Ed. 44, 1221 (2005)

4
1) Ph3P=C=C=O
O O
THF,reflux, 16h
HO 60% O
O O O
2) PhMe, 180 °C, 24h OH
(sealed glass tube)
65%
3) O2 (air)
Rainer, Schobert. et al., Tetrahedron Lett. 42, 4561 (2001)

5
O Co2(CO)8, 4Å MS O
O toluene; K2CO3 O H
MeOH
Me3NO•2H2O
H toluene CO2Me

J.D. Winkler et al., Org. Lett. 7, 1489 (2005)

 Fukuyama Group - Group Meeting Problems
04/26/2005

1
HO
I
Bu3SnH HO
Ts Et3B, O2
N BocN
Boc 80 °C CH2Cl2
82% 0 °C Ts
78%

D. H. Hodgson et al., Org. Lett. 7, 815 (2005)

O NHMDS
O HO Ph
HMPA/THF TBSO
TBS Ph –80 ºC to rt, 2 h

43%

K. Takeda et al., 125th Nihon Yakugakukai Abstract 4, 118 (2005)

3
NHCy
OH CyNC CO2Me
DMAD O

PhH CO2Me
O O reflux
O O
68%

V. Nair et al., Heterocycles 58, 147 (2002)

O D-Proline
4 OBn DMF,r.t. MgBr2.OEt2 OBn
H C18H20O4 O
C9H10O2 98% e.e. BnO Protected D-Glucopyranose
anti:syn 4:1 HO OH Stereoselectivities?
TMSO OR OR
78% C21H24O4Si
65%,d.r. 10:1
R=p-benzyloxy cinnamoyl

D. W. C. MacMillan et al., J. Am. Chem. Soc. 127, 3696 (2005)

5 S MeO2C CO2Me R R R S
Cl (DMAD) DMAD R
S
R + R
S S
xylene, rt xylene, reflux S S R
Cl S
quant 55% (1:1) S R
R = CO2Me

V. A. Ogurtsov et al., Org. Lett. 7, 791 (2005)

 Fukuyama Group - Group Meeting Problems
05/11/2005
Solution: Hoshino

1
1) Cl3CCOCl, Zn-Cu, Et2O AdO Cl

AdO 2) CH2N2, Et2O

3) TMP, (CF3)2CHOH, reflux
53% (3 steps) O

Ad:1-Adamantyl
TMP: 2,2,6,6-tetramethylpiperidine

M. Harmata et al., Org. Lett., 7, 1881 (2005)

2
O iBu
O 1) N2H4, cat AcOH, Δ
O
2) O O
iBu O
O O
OMe OMe
Xylene, Δ

M. Tanabe et al., J. Am. Chem. Soc., 102, 862 (1980)

3
1) H2O2, NaOH 3) DHP, cat. PPTS
MeOH, 10 °C, 88% CH2Cl2, rt, 87%
(S)-carvone THPO
2) LiCl, TFA 4) NaOMe
CO2Me
THF, rt, 95% MeOH, 0 °C, 95%

Steven V. Ley et al., Angew. Chem. Int. Ed., 42, 5996 (2003)

4 Ph
OAc cat. [RuCl2(CO)3]2
Ph
Ph 1,2-dichloroethane OAc
50 °C
68%

OAc cat. [RuCl2(CO)3]2 OAc

+
1,2-dichloroethane toluene*
50 °C; Δ (120 °C)
(excess) 76%
* solvent exchange

K. Ohe, S. Uemura et al., J. Org. Chem., 68, 8505 (2003)

5
OMOM 1) LiTMP (2.4 eq) OMOM
Br dimethylmalonate O
–78 °C, THF, 71% 3) TMS OEt

CH2Cl2, quant. O
2) KOH, MeOH
95%
OMOM OMOMO

S. J. Danishefsky et al., J. Am. Chem. Soc., 118, 9509 (1996)

 Fukuyama Group - Group Meeting Problems
05/18/2005
Solution: Furuya

1
1) Cl(CH2)3OH, Et3N; 3) trisyl azide, Et3N
NaBH4, EtOH, 70% quant. EtO2C
O
N 2) EtO2CCH2COCl, Et3N 4) Cu(acac)2 (5 mol%) N
60% toluene, reflux, 54% O

J. B. Sweeney et al., Org. Lett., 7, 2075 (2005)

2
OH
OMe Ph
MeO CO2Et
· O
O Ph PPh3 Ph
N
Et2O tol; Ph
150 °C
78% (sealed tube) H
N3 CO2Et
46% Ph

P. Molina et al., J. Org. Chem., 56, 4008 (1991)

3 PhNH2
O
CN CO2Me C6H13CHO O
N PhN
Bn
Bn toluene, reflux
C6H13
63% N N
Bn
Bn

J. Zhu et al., Org. Lett., 7, 239 (2005)

TpRuPPh3(CH3CN)PF6
(10%), toluene, 100 ˚C

86 %
I CH2I

Lian J. J. et al, J. Am. Chem. Soc.,127, 4186 (2005)

5 O
OMe 1) PhI(OAc)2 OMe
MeOH, 60 °C
OMe
O OH
OH 2) SeO2 O
O O O O
aq. dioxane
100 °C
OH
MI05146 (05/04/01)
 Fukuyama Group - Group Meeting Problems
06/01/2005
TBDPSO
OTBS OTBDPS 1) TMSCH2MgCl (theoretically 2eq)
1 PMBO
CeCl3 (theoretically 2eq) OTBS
THF, –78°C to rt PMBO
O HO
H H
O 2) Py•HOTf O
MgSO4
BnO2C CH2Cl2, 75% (2 steps)

P. E. Floreancig et al., Angew. Chem. Int. Ed.., in press (2005)

2
1) n-BuLi, THF; 3) NaBH4
MeOH, 0 °C, quant. OAc
OBn 4) mCPBA
THF, 0 °C, quant. OBn
O O 5) Ac2O, DMAP O H
–78 °C, 98% py, 96% O
OTBS
O 2) AcCl, py 6) DBU OTBS
CH2Cl2, 0 °C, 97% MeCN, 80 °C, 84%

P. A. Wender et al., J. Am. Chem. Soc., 119, 12976 (1997)

3
HO
HO 1) LTA (*2 eq), AcOH, rt, 82%

2) K2CO3, MeOH–H2O (8:1), 0°C, 80% O

HO
* theoritical amount

S. Arseniyadis et al., Tetrahedron: Asymmetry 14, 2277 (2003)

O
O Boc
N 1) TFA, CH Cl2, 90% N
OBoc
2) hv, benzene, 68%

J. Aube et al., J. Org. Chem., 68, 8065 (2003)

5 O
1) CbzCl, pyridine
O 8 h, 5 °C H2
O
88% Pd/C

2) hν AcOH
83% 18 h, rt
83% O

W. Oppolzer et al., J. Am. Chem. Soc., 100, 2583 (1978)

 Fukuyama Group - Group Meeting Problems
06/08/2005

1
1) Zn, NH4Cl
OH NaIO4 dioxane, Δ H H
aq. CH3CN; 76% hν O
OH
cyclopentadiene 2) NaH, MeI acetone
70% 55% H H
OMe THF
O
88% (2 steps)

V. Singh et al., Org. Synth., 80, 171 (2003)

2 V. Singh et al., J. Org. Chem., 62, 5310 (1997)

Br Bn N
1)
S O
Ph CO2H, Et3N, benzene
Bn S O
PhHN N
2) Ac2O, Et3N, 52% for 2 steps Ph
3) PhCHO, benzene, reflux, 75% N
Ph Ph

M. Avalos et al., Chem. Commun., 1589 (1990)

3
Me Li PCy3
Cl
Ru H O
O ethylene, Cl PCy Ph (cat.)
, Et3N Me 3
Br Br
TFE, Et2O THF CH2Cl2, rt over night H
–78 °C to rt –78 to –30 °C
50 %
70% 90 %

M. Harmata et al., Org. Lett., ASAP

4
1) aq.HCHO (1.0 eq), PhCHMeNO2(1.0eq) H
15d, rt, 60% N
NH2
2) RaneyNi, H2(500 psi), 60°C, 16h, 85%
N O
3) CHCl3(1.5eq), acetone(2.0eq),
BnEt3N+Cl-(0.04eq), 50%aq.NaOH
10°C, overnight, 92%

Scott. D. Rychnovsky et al., J. Org. Chem., 63, 6363 (1998)

5 (2 eq) EtO2C
Me Me
I Br CO2Et

Pd(OAc) (10 mol%)

P(2-furyl)3 (20 mol%)
Cs2CO3, MeCN, reflux
90%

M. Lautens et al., Angew. Chem. Int. Ed., 39, 1045 (2000)

 Fukuyama Group - Group Meeting Problems
06/14/2005

1 1) BuLi; MeOCOCl, THF

Cl 2) DIBAL, 67% (2 steps)
3) Ac2O, Et3N, DMAP O
Cl CH2Cl2, 97% Li
OH
Co Complex H
4) Co2(CO)8 (1.2 eq), NH3, – 78 °C
CH2Cl2, 98% MeO
OMe 5) MeAl(OCOCF3)(OAr) 75%
CH2Cl2, 77%
Ar = 2,6-(CH3)2-4-(NO2)C6H2

I. Kuwajima et al., J. Org. Chem., 62, 3032 (1997)

2
MeO
MeO 1) TBAF 1) TFAA MeO
SPh 2) MsCl, Py 2) Bu3SnH, AIBN O
3) NaIO4 3) DBU N
MeO
N
TMSO O CO2Me
MeO2C OH O

Y. Tsuda et al., Chem. Pharm. Bull., 46, 906 (1998)

3
O OAc
Ac2O
KOt-Bu cat. ZnCl2
carboxylic acid Ph
t-BuOH AcOH, reflux O
reflux 94%
OBz 53% O

P. Yates et al. J. Am. Chem. Soc., 85, 2937 (1963)

I
4 O
O
N PdCl2(PPh3)2 (5 mol%) Me
Ts Ph
Ph CuI (2.5 mol%) Me
+
butyronitrile-Et3N (1:1)
Me Ph reflux, 48 hr
N O Ph
Me O Ts
86%

Thomas J. J. Müller et al., Angew. Chem. Int. Ed., 44, 153 (2005)

5 MgBr
1. 6 2eq.
Ni(dppp)Cl2 1. PhHgCBr3
(3mol%) C6H6, reflux, 6h

2. Cl2(Cy3P)Ru=CHPh 2. MeLi
Br Br Et2O, -78°C, 10min. 6 6
85% 21% •

N. Krause et al., Eur. J. Org. Chem., 11, 2322 (2005)

 Fukuyama Group - Group Meeting Problems
06/22/2005

1 1) PhMgBr
Br O
CeCl3 1) HBr
THF Trycyclic compound THF Br
(except Ph)
2) t-BuOK 2) m-CPBA
O DMSO CH2Cl2
Ph
30 °C 3) ZnBr2
benzene
reflux

Wei-Dong Z. Li, Org. Lett., 7, ASAP (2005)

2
O
TiCl(Oi-Pr)3 (1 eq) PhCHO, Na2SO4
OH O
EtMgBr (4 eq) Al(OTf)3, –10 °C, 1 h;
OEt
THF/Et2O TiCl4, 1 h
O Ph
51% 69%

K. P. C. Minbiole et al., Org. Lett., 7, 515 (2005)

3
O O3 Ac2O, NEt3 O
t-BuOK NaHCO3 DMAP
CO2Me
t-BuOH-THF CH2Cl2-MeOH PhH
Br –5 °C to rt –70 °C; reflux

70% 67%

A. Srikrishna et al., Tetrahedron Lett., 41, 6643 (2000)

4
MeO MeO
H CO2Me
1) NaH (1 eq), THF, rt, 20 min;
Vilsmeier's reagent, 0.5 h; 4) Al2O3, CH2Cl2 H
O
CH2N2, 0 °C, 5 min, 86% rt, 16 h, 62%
Tricyclic
HO2C OTBDPS aldehyde O
MeO OMe 2) Rh2(mandelate)4, CH2Cl2 5) K2CO3, MeOH-H2O
reflux, 10 min; rt, 1 h, 33% O H
cat. DBU, 2 min, 65% TBDPSO
3) ZnBr2, CH2Cl2
rt, 18 h, 56%
Lewis N. Mander et al., J. Am. Chem. Soc., 120, 1914 (1998)
5
O
CuCN Me3Al (2 eq)
Me OH
THF, 0 °C; BF3·OEt2 CH2I2 (2 eq)
Ph Si Li C17H24OSi
allene, –40 °C; –40 to 0 °C CH2Cl2
Me
–60 °C to rt

58%
F. J. Pulido et al., J. Am. Chem. Soc., 127, 8022 (2005)
 Fukuyama Group - Group Meeting Problems
07/06/2005

1
Ph I2, MeCN-H2O Ph
60 ˚C
Alloc
N CO2Me 92% H2N CO2Me
H
R. H.Szumigala et al, Tetrahedron Lett., 46, 4403(2005)

2
1) CH3CO3H(> 2 eq)
1) SnCl4, CH2Cl2; SnCl4 AcONa O O
COCl DBU, 67% methyl vinyl ketone AcOH, 70°C TBDPSO

2) LDA, THF; CH2Cl2 2) KOH, MeOH;

TMSCl, 75% 61% HCl (pH < 1)
3) TBDPSCl, imidazole
DMF, 33%(3 steps)

J. Clardy et al., J. Am. Chem. Soc., 116, 8378 (1994)

3
3) MsCl, 2,6-lutidine MeO OMe
MeO OMe 1) DIBAL, toluene 50 °C

O O 2) (MeO)2P(O)CHN2 4) CaCO3, wet MeOH

MeO OMe t-BuOK, THF 50 °C CO2Me
70% (2 steps) 72% (2 steps)

V. H. Rawal et al., J. Am. Chem. Soc., 125, 13022 (2003)

4
1) di-tert-butyl malonate
OMe piperidine, AcOH 3) Me3S+(O)·I-, NaH i-Pr
MeO
CHO benzene, reflux, 91% DMF, rt, 94% H

2) 3-methyl-1-butene 4) p-TsOH, toluene

MeO OH hν, benzene, 88% reflux, 55% MeO O H O

S. Ohta et al., Heterocycles, 65, 1099 (2005)

5 O

N SePh

O
OH 1) Bu3P, THF, 0 °C Bu3SnH
81% cat. AIBN
HN C16H21NSe N
2) xs. NaNH2, liq. NH3 PhH
86% reflux Me
Br
40%
C10H18BrNO
Shipman, M. et al., Tetrahedron 58, 7165 (2002)
 Fukuyama Group - Group Meeting Problems
07/13/2005

1 CO2H
1) O3, CH2Cl2, –78 °C
OH +
2) Me2S O
OH O
74% (ca. 4/1)

A. G. Martinez et al., Tetrahedron Lett, 46, 5157 (2005)

2
BnO2C
N
BnO2C H O
t-BuOK DMDO
N
THF CH2Cl2, –45 °C O
O
46% 75%
single diastereomer

R. P. Hsung et al., J. Am. Chem. Soc., 125, 12694 (2003)

3
OTIPS O

1) PhI(CN)OTf
SnBu3 CH2Cl2
MeO –40 °C KF MeO
N
2) LHMDS Al2O3
MeO NHTs DME MeO
–40 °C
K. S. Feldman et al., J. Am. Chem. Soc., 124, 11600 (2002)

4
1) MeNHOH
H H benzene H H
PhO CHO reflux PhO

N 2) H3O+ N
O CHCl3 O O

H H Me
H
PhO CHO MeNHOH H H N
PhO
CHO
N toluene
O rt to reflux N
O

B. Alcaide et al., Tetrahedron Lett., 41, 1647 (2000)

5
O
Ph Me
Ph TiCl4 (3 eq) Ph Me Ph
Ph CDCl3 O
Me H Me rt
O Me
Me O
93%

T. Oshima et al., J. Org. Chem., 69, 4577 (2004)

 Fukuyama Group - Group Meeting Problems
07/27/2005
Solution:Uchida

1
1) DIBAL, toluene, reflux HO
O 2) PhNCO, CH2Cl2, rt
HN 3) HCO2H, 100 °C N
4) KOH, MeOH, reflux

C. H. Heathcock et al., J. Org. Chem., 60, 1120 (1995)

2
H
o-dichlorobenzene S
O S
reflux
S H
46%
(cis/trans = 65/35)

K. Harano et al., Tetrahedron, 52, 13909 (1996)

3
γ-terpinene (radical inhibitor)
O O
toluene, 180 °C (sealed tube)
Ph
70% Ph

as above
O O
150 °C
H Ph
35% Ph

R. L. Danheiser et al., J. Am. Chem. Soc. 120, 9378 (1998)

4
1) NaH
phenyl vinyl sulfoxide 3) TBAF
THF THF
rt, 3 h rt, 2.5 h O
OH
100% 60% (2 steps) O

2) NaHCO3 4) PCC
Ph2O CH2Cl2
TBSO
260 ºC, 25 min 79%

K. Ogasawara et al., Synlett 319 (1996)

T. Mandai et al., Tetrahedron Lett. 4041 (1990)

5
CO2Et
1) BrCH2CO2Et, Zn, THF, reflux, 8h
2) TsN3, Et3N, CH2Cl2, rt, 12h O
N CH2CN
CH3 3) Rh2(OAc)4, ClCH2CH2Cl, reflux, 3h N
CH3

Erick Cuevas-Yanez et al., Tetrahedron., 60, 1505 (2004)

 Fukuyama Group - Group Meeting Problems
08/03/2005
O
1 1) hν 3) RuO2, NaIO4
acetone CCl4, H2O, MeCN; OH H
75% 2M aq.H2SO4; H
O
2) DPPA, Et3N NaHCO3
HO2C dioxane, Δ 55% H
89% O

J. K. Cowell et al., Tetrahedron Lett., 37, 2177(1996)

2
1) CH2N2 4) NaI CO2Me
O Et2O, 0 ºC MeCN, reflux
C13H16ClNO3
Cl 2) BF3• Et2O 5) PhSiH3, CsF N
Cl(CH2)3CN MeCN, reflux O
0 ºC to rt 6) DDQ
59% (2 steps) 48% (3 steps)
3) cat. PdCl2, CO
NaOAc, CuCl2
MeOH, 67%
E. Vedejs et al., J. Org. Chem., 58, 1341 (1993)
3
1) (n-Bu3Sn)2 3) LTA (1 eq)
O n-BuLi; MeI CH2Cl2
–60 °C to rt NH2 OH
THF, –78 °C
4) LAH, Et2O, rt Me
2) NH2OH•HCl H
NaOAc
MeOH, rt

H. Nishiyama et al., J. Am. Chem. Soc. 107, 5310 (1985)

O
4 CO2Et

, Bu3P TFAA, CH2Cl2 O

toluene, rt; NaIO4 0 °C, 10 min; N
O
SEt
O N3 EtSCH2COCl, Δ H2O-MeOH, rt TFA, rt, 2 h CO2Et

44% 95% 76%

A. Padwa et al., Org. Lett. 7, 1339 (2005)

5
Hex 1) ClPh2SiSiMe2Ph 3) c-HexCHO OH Hex
Et3N, DMAP TiCl4
HO
c-Hex
2) t-OcNC (8 mol%) 76%
Me Pd(acac)2 (2 mol%) Me
toluene;
n-BuLi, THF
86%
Y. Ito et al., J. Org. Chem., 61, 4884 (1996)
 Fukuyama Group - Group Meeting Problems
08/10/2005

1 O O
1)
Cl Cl
S Zn
–78 °C to rt, 5 h 1) Pd/C, H2 (4 atm), 15 h
NH N
Et 2) toluene, reflux 2) LAH, THF
O2 N 3 h, 66% 0 °C to reflux, 20 h N
H
3) AcOH, 2 h Et
A. Padwa et al., Org. Lett., 7, 2925(2005)

2
1) O
Me2N OTBS , MeCN; 1) TFA, CH2Cl2
MeO2C
O NBoc HF·pyr, 25 °C 2) KOTMS, Et2O
2) tol, reflux 3) Pb(OAc)4, DMF N
60% (2 steps) 0 °C H
58% (3 steps)

A. Padwa et al., J. Org. Chem., ASAP

3 OMe
(CO)5Cr
Me
I
hν (visible light) H H
ZnCl2, CO (5 atm) I2
N N OMe
Bn THF, rt MeCN, rt Me
O
71% 69%

Hegedus, L. S. et al., J. Org. Chem., 61, 2871 (1996)

4
Ph2
, 1 Si
O
>40% Mes N N Mes
Ph Ph
Si OMe Cl
O Ru
MeO Cl
Ph
Ph2
, 1 Si PCy3
O
Grubbs 2nd
>50%
1
OMe

D. Lee et al., J. Am. Chem. Soc., 127, 9410 (2005)

5
NH2 NC
1. MeOH/THF, 48h, 67% Bn O
H
2. 2 eq. KHMDS N N
O 2 eq. Br O Br
H
O O
Br O CHO 3. cat. 1, (see problem 4)
HO2C N H H N
H CH2Cl2, 69%

S. Screiber et al., Org. Lett., 2, 709 (2000)

 Fukuyama Group - Group Meeting Problems
09/07/2005

1 SO2Ph
Me furanylamine•HCl
CHO NEt3, 3 Å MS; Br2 Toluene, reflux Me H
H
SO2Ph NaBH4, 91% 1:1 AcOH:water 70% N
0 °C H
O
77%

D. Y. Gin et al., Org. Lett., 7, 3323 (2005)

2
1) MgBr (1.3 eq)
O
Bn
oxalyl chloride THF, –78 °C N O
NC NH2+Cl– C11H8ON2Cl2 MeO
NH2
Bn o-dichlorobenzene 2) reflux (open air)
100 °C 3) MeOH, HCl

56 % 29% (in 3 steps)

G. J. Hoornaert et al., Eur. J. Org. Chem., 2005, 2941

3
iPr
n-BuLi, THF, –78 °C;
Cr(CO)6, –78 °C to rt;
iPr
Et3OBF4, 0 °C; pyridine
HNMe2, 0 °C 80 °C, 4 day
O
89% 68%

A. de Meijere et al., Eur. J. Org. Chem., 2802 (2005)

4
methyl acrylate O
methyl vinyl ketone Cl2CHCO2H
CHO toluene, 80 °C;
DABCO O

CHO dioxane-H2O, rt xs. p-TsOH•H2O, reflux O

V. Nair et al., Synthesis, 2005, 1967

5
1) dry HCl (gas), MeOH, 0 °C, 95%
2) aq. NaOCl, 0 °C, 100% CO2H
CN
3) aq. NaOH, rt; purification, 53% NH2

D. H. G. Crout et al., J. Chem. Soc., Perkin Trans. 1, 3537 (1994)

 Fukuyama Group - Group Meeting Problems
09/14/2005

1
OH 1) DIBAL-H, CH2Cl2
t-BuO2H, VO(acac)2 PIFA –15 °C to 0 °C
C11H23
benzene, 0 °C to rt. O O
H2O 2) Ag2CO3, benzene
C11H23 reflux, 57% (2 steps) OH
96% 72%

Y. Kita et al., Angew. Chem. Int. Ed., 44, 2 (2005)

2
O
O O
CrO3, LDA;
O 3,5-dimethylpyrazole TMSCl; 1) mCPBA

CH2Cl2 3-butyn-2-one; 2) Pd(PPh3)4

O
TBAF PBu3
MeCN O
O

T. Tanaka et al., J. Org. Chem., 124, 7107 (2001)

3
Ph • Ph Ph
TsOH
CO2Et EtOH LiHMDS CO2Et CO2Et
+
Toluene THF THF
TMSO 130ºC –78ºC O O

46% 70% 67% 23 : 1

M. E. Jung et al., J, Am. Chem. Soc., 32, 11206 (2005)

4
1) (Ph3P)3RhCl, H2 (40 psi)
cat. Rh2(S-DOSP)4 EtOH O
CO2Me cyclopentadiene 2) LiOH, MeOH/H2O
C10H12O2
N2 hexane, –78 °C 3) DPPA, Et3N
mesitylene, rt;
70% NH4Cl, dioxane-H2O
reflux

13% (3 steps)

H. M. L. Davies et al., J. Am. Chem. Soc., 120, 3326 (1998)

5
cat. Rh2(OAc)4 Me
N ClCH2CH2Cl, 130 °C;
N Ph
O Ph
Ph Me2AlCl, –40 °C Me
HO
68% (>20:1 dr)

B. M. Stoltz et al., J. Am. Chem. Soc., 124, 12426 (2002)

 Fukuyama Group - Group Meeting Problems Ver. 2
09/21/2005

1 S
DBN
PhS Cl CH2Cl2
t-BuNC Ph
rt; N S
N Ph N t-Bu
CH2Cl2 H2O SPh
rt 80%

Morel, G. et al., Eur. J. Org. Chem. 1998, 2631.

2
O
O
1) PCC, celite 1) Rh2(OAc)4, allyl alcohol
benzene, reflux CH2Cl2, 95%
C15H13N3O2
2) TsNHNH2, HCl 2) MgBr, THF, 0 °C HO H
O
N THF, reflux; evp; 3) xylenes, reflux O
Me basic Al2O3 89% (2 steps) N
59% (2 steps) Me
C15H15NO2
racemic J. L. Wood et al., J. Am. Chem. Soc. 1999, 121, 6326.

3 1) KOCN
H AcOH 1) PhMgBr OH
BnO H H
pyr., Et3N, THF-CH2Cl2 BnO
rt, 85% tricyclic –55 °C
NH compound N NH OPMB
Me Me
H 2) SOCl2 (except Bn,
OPMB 2) (MeO)3P H
BnO imidazole PMB) O
MeOH BnO
CH2Cl2 50 °C
–78 °C to rt 84% (2 steps)
81%
S. M. Weinreb et al., J. Am. Chem. Soc. 2001, 123, 8851.
S. M. Weinreb et al., J. Am. Chem. Soc. 2002, 124, 3939.

4
MeO

glyoxylic acid monohydrate 1) 4N HCl

4-methoxyphenylboronic acid 1,4-dioxane, rt, 3hr
N O
HN CH2Cl2, rt, 4hr N
2) isovaleraldehyde N
HN O O
2,6-dimethylphenylisocyanide H
MeOH/H2O (8:2), rt, 24hr
O

David E. Portlock et al., T. Lett. 2002, 43, 6845.

Dinabadhu Naskar et al., T. Lett. 2003, 44, 6297.

5
O
200 °C O O
+
24 h

C. A. Cupas et al., J. Am. Chem. Soc. 1970, 92, 3237.

 Fukuyama Group - Group Meeting Problems
10/04/2005

1
O
O H
LiCH=CH2, THF, –78 ºC;

toluene –78 ºC to rt;

110 ºC H
OTMS aq. NaHCO3 OH
98% 69%

H. W. Moore., J. Org. Chem. 1998, 63, 6905.

2 Rh(PPh3)3Cl (5 mol%)
AlCl3 (10 mol%)
2-amino-3-picoline (60 mol%)
MeCHO, cyclohexylamine O
nC H nC H nC H
5 11 5 11
5 11
toluene, 130 ºC, 12 h; Me
H+
90%

Chul-Ho Jun et al., J. Am. Chem. Soc. 2003, 124, 6372.

3
O
ClCH2I, n-BuLi TFA NaH
4
THF-Et2O, –100 °C Et2O, 0 °C DMF, rt
Me
98% O
95% 98%

T. H. Kinstle et al., Tetrahedron Lett. 2005, 46, 6449.

4
CHO HO O
O N
NO2 , K2CO3
O
H2O
rt, 1 h O

95%

J. C. Menendez et al., Org. Lett. 2005, 7, 2197.

OAc
5 I
O
1eq, I2 1.1 eq,
TMSN3 10 mol%,
60°C, 15h I
O 0.91 mmol/mmol I2
or
or H2O2, NaN3 3 eq, I2 1 eq 1.31 mmol/mmol I2
Ac2O , H2O
0°C to 40 °C, 13h

J. Barluenga et al., Angew. Chem. Int.Ed. 2005, 44, 5851.

 Fukuyama Group - Group Meeting Problems
10/18/2005
1 O O SO2Ph
1) PhSCl, Et3N
CH2Cl2
OH 0 °C to rt, 3 h NaOMe, MeOH O
A 59%
2) H2O2, AcOH O O
reflux, 10 h O
68 % (2 steps)
3) Br2, AcOH
rt, 8 h, 87% NaOMe, MeOH
44% SO2Ph

S. H. Watterson, Z. Ni, S. S. Murphree and A. Padwa, Org. Synth., Coll. Vol. IX., 1998, 207.

2
1) n-BuLi;
work up (acidic), 61%
O O
N2
2) O
O TMS H , n-BuLi, 85%
+ NC
I
PPh3 3) O3; PPh3, 79%
4) KOH, THF-H2O
99% O

D. F. Taber et al., J. Org. Chem., 2005, ASAP.

3
Ph
O CO2Me 1) NaOMe, MeOH HO
hυ (350 nm) HO CO2Me
OH tricyclic compound 65 °C, 90%
(except Ph)
CH3CN 2) Me4NBH(OAc)3
O Ph Ph
rt, 2 h CH3CN-AcOH O Ph
95%
56%

J. A. Porco, Jr. et al., J. Am. Chem. Soc., 2004, 126, 13620.

4

POCl3 Boc2O LTA

MeO NHAc MeO
toluene CHCl3 CH2Cl2-AcOH NBoc
MeO reflux 60 °C rt MeO
O
95-96% 90-92% (2 steps)

G. R. Lenz et al., Org. Synth., Coll. Vol. IX., 1998, 268.

5
Me SO2Ph Me
C t-BuLi Me
Me S O
THF
–100 °C, 1 h O
I
~50%

J. K. Crandall et al., J. Org. Chem., 1992, 57, 2993.

 Fukuyama Group - Group Meeting Problems
10/25/2005
1

O H
MeO2C 1) hν, CH2Cl2 3) 210 °C
+
2) Ph3P CH2 toluene
MeO2C
Me 88% 95% Me

P. A. Wender et al., J. Org. Chem., 367 (1980)

2 Me
N I
1) NaH
Cl
p-BrC6H4CHO (1.2 eq) N
N THF, reflux, 79% Me (cat.) N

N Cl 2) NaOMe, MeOH, reflux, 71% N OMe

3) MeMgI, THF, 88%
4) KCN, DMF, 80 °C, 86%

A. Miyashita et al., Chem. Pharm. Bull., 46, 199 (1998)

3
Hex
O Hex MgBr ZnBr2 aq. HCl
SiMe3 THF THF OH
–80 °C to reflux; –60 °C to rt;

I. Marek et al., Org. Lett., ASAP

4
F3C CN

S 1) CH2N2 NC
CH2N2 NC CF3 Et2O, rt S CF3
Cyclic
CN
Et2O, –78 °C CDCl3, 40 °C iminoketene
2) CHCl3, 50 °C
O O CF3

K. Polborn et al., Eur. J. Org. Chem., 3781 (2005)

5
O
CO2Me
1) OEt 2) hν ,hexane, 95% 5) AIBN, Bu3SnH
OSiMe3 3) 10% HCl benzene, reflux, 92%
CO2Me
O ZnCl2, HMPA 4) (imid)2C=S
CuBr-Me2S DMAP, THF
O Et2O-THF 85% (2 steps)
HO
83%

M. T. Crimmins et al., Tetrahedron Lett., 37, 8703 (1996)

 Fukuyama Group - Group Meeting Problems
11/02/2005
1
MeO2CNSO MeO2CN=S=NCO2Me H
O O
benzene, 0 °C; HMPT toluene, Δ;
NH
PhMgBr EtOH (MeO)3P, MeOH H
THF, –60 °C reflux NHCO2Me
73%
86% 44%

S. M. Weinreb et al., J. Org. Chem., 63, 7594 (1998)

2
1) n-Bu3SnH
I AIBN
S benzene, Δ 3) TsN3, Et2NH
O
O 2) NaH 4) CuSO4
HCO2Me toluene, Δ

G. Pattenden et al., Org. Biomol. Chem., 3, 340 (2005)

3 O
n-BuLi, THF PMP
OH
–78 °C to –25 °C;
W(CO)5
OMe
OMe
PMP

71%

J. Barluenga et al., Angew. Chem. Int. Ed., 44, 5875 (2005)

4
[Cp*Ru(MeCN)3]PF6 (cat.) 1) MCPBA, CH2Cl2, 0 °C, 99% OH
OH Et3SiH 2) MeMgBr, ether, –20 °C to rt, 64%

acetone 3) TFA, ether, 75% 5

5

99%

B. M. Trost et al., Org. Lett., 7, 4911 (2005)

5 Me
N

Me TIPS
N2 N
Rh2(OAc)4 MgI2 (1 eq)

N O benzene THF N O
H H
TIPS

E. M.Carreira et al., Angew. Chem. Int. Ed., 42, 2583 (2003)

 Fukuyama Group - Group Meeting Problems
11/08/2005

1
O Cl R
N
hν Cl2 ClMg
NR
N O CH2Cl2 THF
n-Bu rt 0 °C
OH
R = n-Bu

S. M. Sieburth et al., Org. Lett., ASAP

2
CO2Et
NaNO2
NH2 aq HCl; Et3N N
N
O NaOAc benzene
O O reflux
O
Me OEt
Cl
L. Garanti et al., J. Org. Chem., 42, 1389 (1977)

3
1)Ethyl isocyanatoacetate O
CO2Et PhCH2CHO, S Pyridine, 45℃, 2hr
EtO2C N
Ph
CN Et3N, DMF 2)NaOEt, EtOH O N S
45℃, 9hr rt, 3hr H

45% 96%(2steps)
Takeda pat. JP H08-73467

4
H OH
OEt
70% aq. HClO4 hν N
perchlorate
EtO salt
AcOH CH3CN-H2O O
CHO
H
60% 61%

B. Ganem et al., J. Am. Chem. Soc. 123, 10425 (2001)

In Science of Synthesis; E. J. Thomas, Ed.; Thieme, Stuttgart, 14, 128 (2003)

5 4)
1) cat. NHPI, O2 MgBr 5) TsNHNH2;
cat. Co(acac)2 cat. CuBr•SMe2 NaBH3CN
MeCN, 50 °C, 60% TMSCl ZnCl2

2) LDA, TBSCl THF-HMPA THF, reflux

THF-HMPA, 0 °C –78 °C;
OPiv 3) Pd(OAc)2, O2 10% HCl, 0 °C 75% PivO
DMSO, 45 °C
74% (2 steps) 88%

NHPI = N-hydroxyphthalimide
M. Ihara et al., Org. Lett. 7, 3929 (2005)
 Fukuyama Group - Group Meeting Problems
11/22/2005

1
MgBr MesN NMes
O LDA Ph
Cl
CuBr•Me2S THF; Cl Ru O
TMSCl MeCHO; cat. PCy3 H

THF MsCl, Py; CH2Cl2

–78 °C Et3N H
90%
97% 88%
M. Koreeda et al., Org. Lett., 6, 3719 (2004)

2
O
MeO2C H CO2Me
[Rh(dppe)]ClO4 (10 mol%)
MeO2C CO2Me
O
ClCH2CH2Cl
H 65 °C H H
44%

M. Mori et al., 88th Synposium on Organic Synthesis, Japan

3 4) Me O
1) AcOK Me
MeOH, reflux N Br
Me N Me
2) H2, Pd/C Br
Me Et EtOAc,rt O Me Et

Me iPr Me H iPr
3) Zn(OAc)2 NaHCO3
AcOH, reflux Hexane, reflux
64% (3 stteps) H H
TsO AcO Br
R. M. Moriarty et al., J. Org. Chem. 70, 7624 (2005)

4
Me LHMDS Me
Me LiTMP THF, –78 °C; Me
CH2Br2 n-BuLi; HNTf2
OMe Br
Me O THF TIPSOTf CH2Br2
–78 °C –78 to 0 °C –78 °C to rt O
Me
76% 92% 81%

S. A. Kozmin et al., J. Am .Chem. Soc. 127, 13512 (2005)

5

1) NaN3, DMF PPh3, toluene

Ph CHO rt, 51% Δ, 3-4 h; CO2Me

2) CHCl3, Δ, 80% CO2Me N Ph

Cl
44%

T. Nakata et al., Heterocycles 48, 2551 (1998)

 Fukuyama Group - Group Meeting Problems
12/14/2005

1
O 220 °C H4N2, H2O; OH
OH
Et3N, toluene KOH
microwaves
82%
87%

L. Barriault et al., Org. Lett., 7, 4589 (2005)

2
O Ph
Ph
Ph TsOH (3 eq)
O
Ph Ph H
CDCl3 Ph
Ph H rt
O
O

T. Oshima et al., J. Org. Chem., 70, 8364 (2005)

3
I 1) t-BuLi
THF-HMPA, –78 °C; O
Li SiMe3 PhCHO, –78 °C to rt, 57%
HO Ph
SiPh2
THF 2) mCPBA, CH2Cl2;
–78 °C to rt aq. H2SO4
3) aq. H2O2
58% 30% (2 steps)
K. Utimoto et al., Bull. Chem. Soc. Jpn., 67, 1694 (1994)

4
1) cyclooctyne, Δ
2) hν 4) m-CPBA (1 eq) MeO2C
O
3) toluene or xylene, Δ 5) hν MeO2C O

MeO2C CO2Me O
H

W. Tochtermann et al., Eur. J. Org. Chem., 4231 (2005)

5
N
1) KOH, MeOH 1) O , CH2Cl2, rt
Cl , Na2CO3 C6H7ClO2
Cl 85 °C 60 hr, 65% CO2Me
N
Cl CCl4, 170 °C 2) acidic resin (conteining 2) DMSO, 100 °C
Cl
CH2Cl2, rt cyclopropane 5 hr, 83% O
ring)

A. de Meijere et al., J. Org. Chem., 64, 755 (1999)

 Fukuyama Group - Group Meeting Problems
12/21/2005

1
iPr Me A, p-TsOH•H2O
iPr Me
MgSO4 10 mol% SnCl4 hv
OH H H
HO CH2Cl2, –20 °C CH2Cl2/CH3CN(1:1) 1,4-dioxane Me
–50 °C rt O
75% H H
88% 66%
OHC
TMS TIPSO TMS
A= OTIPS
Me
L. E. Overman et al., Org. Lett., 2, 2683 (2000)
2
CN
O
1) Raney Ni, H2 H
t-BuO2C H
EtOH, 74–96% tetracyclic HBr, AcOH, CH2Cl2; OH
compound N Me
Me 2) HCl (except Bn) MeOH, NaOH
H MeOH, 70 °C
TBDPSO OBn
O 96% 95% O
4

D. A. Evans et al., Angew. Chem. Int. Ed., 44, 6038 (2005)

3

Si(t-Bu)2 (> 2 eq) SiOBn(t-Bu)2

OBn
AgO2CCF3
SiH(t-Bu)2

K. A. Woerpel et al., Org. Lett., 7, 5531 (2005)

4
MgBr OBn
O
(2 eq) CHO 1) Ac2O, Et3N [Rh(CO)2Cl2]2
(Cp)2TiCl2 LDA DMAP, CH2Cl2 (0.5 mol%)

CO2Me THF THF 2) NaCN toluene

–40 °C to rt –78 °C DMSO reflux H OBn
130 °C

P. A. Wender et al., Org. Lett., 2, 2323 (2000)

5 1) LDA, THF, –78 °C;

cyclobutanone H3PO4 CN
2) Ac2O, DMAP, Py LiCH2CN (5 eqb) H2O
O C9H9NO O
S Cl 3) basea, THF THF AcOH
Tol
93% (3 steps) –78 °C to rt reflux
91% 99% C9H9NO

a: N-lithio-2-piperidone or lithium diphenyl amide

b: theoretical amount: 3 eq

T. Satoh et al., Tetrahedron Lett., 46, 3767 (2005)

 Fukuyama Group - Group Meeting Problems Ver.2
01/10/2006

1 NaNH2 (3.0 eq)

A
O O liq. NH3-Et2O;
Cl Cl NH4Cl
HO
O OH
A (neat), rt; 1) LiOH, THF-MeOH-H2O
NBS, THF-H2O; 60 °C
O O
O t-BuOK, t-BuOH 2) NBS, PPh3, DMF
3) Zn, NH4Cl, EtOH HO

E. Nakamura et al., Tetrahedron Lett., 48, 2045 (1992)

D. L. Boger et al., J. Org. Chem., 59, 3453 (1994)
2 2 ClO4

Ph2C CPh2
NEt2
MeO MeO NEt2
PhS

OH MeCN –40 °C, 0.5 h

–40 °C, 0.5 h O

J. Ichikawa et al., J. Am. Chem. Soc., 127, 9696 (2005)

3
MeMgI KOH I2
NBn NBn
O O Et2O MeOH, H2O MeOH MeO
–20 °C to rt rt, 3 hr 70 °C, 130 min
30 min; H2O
100% 70%
80%

J. Richard Heys et al., J. Org. Chem., 54, 4702 (1989)

4

1) LHMDS, hexane
CH2=C(Me)CO2Me
1) K2CO3, MeOH, 90% O
O –10 °C to rt, 70%
C15H22O5
2) O3, CH2Cl2-MeOH 2) p-TsOH·H2O
–70 °C; Ac2O, Et3N PhH, reflux, 65% CO2Me
C11H16O DMAP, PhH, reflux
60%

A. Srikrishna et al., Tetrahedron Lett., 47, 363 (2006)

5
H
CN 1) TBDMSOTf, CH2Cl2, rt;
H O Ph N
MeMgI, Et2O, –78 °C Me
N
Ph
2) PPTS, CH2Cl2 O
OMe 70% (2 steps)
OMe

H. -P. Husson et al., J. Org. Chem., 57, 4211 (1992)

 Fukuyama Group - Group Meeting Problems
01/18/2006

1
CO2Me
MeO 1) EtNO2, t-BuOK 3) SnCl4 5) Ra-Ni, H2
t-BuOH, 72% CH2Cl2, –78 ºC tetracyclic MeOH;
O compound HO
N
2) Ac2O, DMAP 4) PhH, 60 ºC NaOMe
Et2O, 79% 92% (2 steps) C16H25NO5 79% O

S. C. Denmark et al., J. Org. Chem., ASAP

2
NO2 pyrrolidine (2 eq); NC Ph
PhCHO (0.5 eq); AcCl (0.5 eq)
N N O benzene benzene/hexane N CN
H O O
90%

M. Ariga et al., J. Org. Chem., 64, 6476 (1999)

3 1) maleic anhydride 3) aq. KOH

neat, 170 °C MeOH, 50 °C
90% 98% 5) AgNO3

2) hν, acetone 4) Pb(OAc)4, Py MeOH-H2O

28% CH3CN, 55 °C 98%
47%

S. F. Nelsen et al., J. Am. Chem. Soc., 113, 7882 (1991)

W. G. Dauben et al., J. am. Chem. Soc., 93, 1446 (1971)

4
O
O nBu
O nBu
1 mol % AuCl(PPh3)/AgSbF6
O
CH2Cl2, rt, 2 h
Ph
N N H Ph
H 98% H

L. Zhang, J. Am. Chem. Soc., 127, 16804 (2005)

5
1) NaClO2, NaH2PO4
2-Methyl-2-butene
AcO Cu(hfacac)2 H
t-BuOH, H2O, rt AcO
O + H
AcO
OHC 2) MeONa, MeOH, rt; CH2Cl2 H H H
H O H (COCl)2, benzene, rt; reflux O
O
CH2N2, Et2O, 0 °C H O
77% (2 steps) 83%
2 : 1

J. L. Castro et al., Synthesis, 3398 (2005)

 Fukuyama Group - Group Meeting Problems
01/25/2006
1
1) t-BuLi (1 eq), Et2O;
NMe2 1,2-dibromoethane (1 eq), 56%
2) NBS (1 eq), MeOH/CH2Cl2

N 3) TBAF N
TIPS 4) Boc2O, DMAP, 72% (3 steps)
5) Bu Sn Boc
3 ,Pd(PPh3), 40%
*3), 4) Exchange TIPS with Boc, simply.
Snieckus, V. et al., Org. Lett., 4, 815 (2002)
2 1) n-BuLi (1.05 eq)
THF, –78 °C; 3) O
TESCl;
s-BuLi (1.2 eq); Ph Cl
MsCl Et3N
O
65% 82%
HO Primary Amine Ph N
2) NH3, MeOH 4) toluene H
40 °C, 15 h 110 °C; Me
aqueous workup Z only
(SN2 reaction)
27% 81%

Danishefsky, S. J. et al., J. Am. Chem. Soc., 126, 6347 (2004)

3
TMSO OTMS
1)

BF3·OEt2, CH2Cl2 O
–78 to 10 °C, 3 hr
O O 93%
CO2Me
2) BF3·OEt2, H2O O
CO2Me CO2Me
CH2Cl2, 16 hr MeO2C
47%
Curran. D. P. et al., J. Org. Chem., 60, 345 (1995)

4 3) cat. Rh2(OAc)4
O O O OH
1) TsNHNH2 methyl propiolate
THF, 50 °C PhH, 60 °C, 75% Me
RO OR MeO
O Me 2) Basic Al2O3 4) TfOH, CH2Cl2 Me OH
O CH2Cl2, rt rt, 41%
>71% (2 steps) OH
Me

R= TMS J. L. Wood et al., J. Am. Chem. Soc., 123, 2097 (2001)

5
1) Me +N CO2-
3 1) Mg
NaH, THF, reflux; t -Butyl bromoacetate O
H3O+, 92% Et2O, 84%
BnO OH C13H16O2
2) 180 °C, 0.1 mmHg 2) KOH, MeOH
85% 24 h; H3O+, quant
3) AcOK, Ac2O, rt, 2 h; OBn
Δ, 3 h, 93 %

Rosini. G. et al., Org. Lett., 2, 4145 (2000)

 Keys to the Problems (02/15/2004)

1 O
H
CO2 CO2 CO2
Me H N N A N

OH H SMe2
H
N
CO2 Me Me Me O
Ph

CO2 CO2H CO2H

N N N

H2O HO
B Me Me
Me2S
Me
O O
O Ph Ph Ph

Ph3P
O H2C PPh3 Ph3P
O
H O
Me Me Me Me
C
O O O O H
Ph Ph Ph Ph
Me N Me

Me Me

Ni
Ni
Me O Me D O Me Me
O
O
Ph O Ph O
Ph Cl Ph Ph Ph O
Ph
O
Johnson, J. S. et al. Org. Lett. 2006, 8, 573.
A: to avoid repulsion between the alkyl chain and hydrogen atom on indole. For stereochemistry, see: D. W. C.
MacMillan et al., J. Am. Chem. Soc. 2005, 127, 3240. B: Corey-Chaykovsky Reaction. C: Wittig reaction. D:
Nucleophilic attack by Ni to form π-allyl complex.

2 O tBu O
I
O OK
I I I Pd0 Pd
H C C
H A B
O O O O

H
tBu O
Br

Fukuyama Group - Group Meeting Problems

 Keys to the Problems (02/15/2006)

I N3
Pd
Pd
B C N N N
O O

–
N
N N N
D E
N N
O
O
Grigg, R. et al. Tetrahedron Lett. 1998, 39, 435.
A: Isomerization of triple bond to form allene. B: Intramolecular Heck reaction. C: π-allyl complex formation. D:
Intermolecular 1,3-dipolar reaction. A double bond in norbordiene is more reactive than usual one. E: Retro Diels-
Alder reaction to eliminate cyclopentadiene.
HH
O O O
OMe OMe O H
MeO MeO MeO
CH hν hν
3 CH2
2

MeO O A MeO O B Me O
A
H
HO
O H HO
MeO O
MeO
C Me O
Me O
B
Me MgI F3B
F3B
O Me Me
OMe HO OMe HO OMe
MeO MeO MeO

Me O Me O Me O

A
Me Me
OMe
MeO MeO O
D
Me O Me O
H

F3B
H3Al H
Me F3B
O HO OH Me
O Li MeO HO OH
MeO MeO
MeO O
Me O Me O
B

Fukuyama Group - Group Meeting Problems

 Keys to the Problems (02/15/2006)

Me Me
OH
MeO MeO O
D
Me O Me O
H

Venkateswaran, R. V. et al. Tetrahedron Lett. 2004, 45, 983.

A: [2+2] photocyclization. B: Generation of a triplet diradical. C: Abstraction of a hydrogen atom. D: Formation of
carbocation induced by Lewis-acid. The cation is stabilized by the oxygen atom at ortho position.

H H
workup
4 H H
O O A
O O O HO
H O O
tBuO H BH3 Na

H2
Pd/C

B OH OH OH C O
HO HO O O
H Pb(OAc)2 –Pb(OAc)2
Pb(OAc)3
OAc OAc

Hopkins, P. B. et al. Tetrahedron Lett. 1988, 29, 4229.

A: Oxy-Cope rearrangement. B: Reduction from less hindered face. C: Oxidation with lead(IV) tetraactate (LTA),
followed by generation of lead(II) diacetate.

Fukuyama Group - Group Meeting Problems

 Keys to the Problems (02/15/2006)

O Me O Me O H O Me OH
CONHBn hν
5 NHBn NHBn
A
Me Me Me
CO2Me CO2Me CO2Me

MeOH
H2O
O Me OH OOMe O OMe O
Me O Me
NHBn NHBn NHBn
Me Me Me
CO2Me OMe OMe
O HO
H
H
MeO OH O O O O HO
HOMe
Me NHBn Me NHBn Me NHBn
H
Me OMe Me OMe Me OMe
O O O O O O

O O
Me OMe

Me OMe
O O
Barran, P. S. et al. Angew. Chem. Int. Ed. 2006, 45, 249.
A: [2+2] photocyclic reaction.

Fukuyama Group - Group Meeting Problems

 Fukuyama Group - Group Meeting Problems
03/01/2006

1
Br HgCl2
1,3-dithiane
O n-BuLi NaH CaCO3 i-Pr
O
i-Pr Me Me
THF, –78ºC MeCN-H2O O

63%

A. Bhattacharjya et al., Org. Lett., 7, 207 (2005)

2 nC H
5 13
nC H
5 13
1) acetone, TFA, TFAA, 84% HN
HN CO2tBu 2) hν
O
3) NaBH4, EtOH O
4) NaH, THF, 60% (2 steps)
O O
O

J. D. Winkler et al., J. Am. Chem. Soc., 111, 4852 (1989)

3
N N
3) Bu3SnH(0.01eq), H
1) HBBr2·SMe2, CH2Cl2 NaBH3CN(2.5 eq), THF Bu
n-Bu
2) O , THF 4) Me OH
Me
N
Me , benzene; H2O, reflux OH
O
H

80 % (2steps)

R. A. Batey et al., Angew. Chem. Int. Ed., 38, 1798 (1999)

4 O SEM
N
O SEM
N
1) MeOTf, CH2Cl2

2) Na2Fe(CO)4 MeN
N NMP, CO
50 °C
O
59% (2 steps)

L. E. Overman et al., J. Am. Chem. Soc., 127, 18054 (2005)

L. E. Overman et al., J. Org. Chem., 57, 1035 (1992)
5
NHTs
N
Me 3) S Me
Me 1) isopropenyl lithium MeS SNa Me
Et2O, 0 °C MeCN MeS
O
2) PBr3 4) NaH, THF
H Et2O, 0 °C reflux, 6 h H

D. A. Evans et al., Tetrahedron Lett., 47, 4691 (1973)

 Fukuyama Group - Group Meeting Problems
03/08/2006

1
OMs 1) NH2NH2·H2O
neat, rt O
O O TBSO OAc
2) TBSOTf, pyr.
CH2Cl2, 0 °C
O O 85 % (2 steps) O O
3) LTA, toluene, rt
48 %

A. Vassella et al., Helv. Chim. Acta, 87, 2405 (2004)

2
O3S O
NEt t-BuO
t-BuO
i-Pr2NEt TMS N C S Fmoc N O
FmocHN CO2H MeCN CH2Cl2 NH
S

V. L. Boyd et al., Tetrahedron Lett., 31, 3849 (1990)

CO2Me
MeO2C O
Cu(acac)2 (10 mol%)
N
N2 toluene, reflux
N
O
cis : trans = 3.6 : 1

F. G. West et al., Org. Lett., 7, 2949 (2005)

4
1) p-anisidine
O CO2Et
OH POCl3, DMF p-TsOH·H2O
75 °C; tol, reflux (Dean-Stark)
C10H6O3
H2O 2) CH2=C=CHCO2Et O N
O PPh3 (cat)
80% benzene, reflux, 55% PMP

P. S. Ishar et al., Org. Lett., 2, 2023 (2000)

5
O 1) NH2OH.HCl
1) DIBAL, toluene
NaOAc, MeOH
rt, 24h -78 °C,2h, 100% HN
Tricyclic
HO
compound
2) 190 °C 2) n-PrP+Ph3Br-
NC NC (sealed tube) KHMDS, THF
toluene, 3.5h -40 °C,24h, 62%
59% (2steps) 3) H2, 10%Pd/C
MeOH, 69%
Robert A. S. et al., J. Org. Chem ., 69, 1598 (2004)
 Fukuyama Group - Group Meeting Problems
03/14/2006

1
O Ti(Oi-Pr)4 (1.4 eq)
c C5H9MgCl (4.5 eq)
N
N R
R THF, 20 ºC

87%
MeO
R=

Y. Six et al., Euro. J. Org. Chem., 70, 4654 (2005)

2 O
OTBDPS O
H O H
SnCl4 O O

CH2Cl2 H OTBDPS
O – 78 ºC
O H O
48%

L. Barriault et al., Org. Lett., 7, 5921 (2005)

3
1) Cl 2) mCPBA (1.0eq)
CH2Cl2 PhO
Me PhO OMe
12 h, rt
HN K2CO3, NaI 90% Me N

N O 12 h, reflux 3) MeOH
80% 2 h, reflux N O
Me
86% Me

M. Abass et al., Heterocycles, 65, 901 (2005)

4
OAc O
1) LAH, THF, rt
O O
76% (2 steps)
+ + H
H
OEE 2) ClSO3H
CH2Cl2, –78 °C
3) H2, Pd/C 25 : 30 : 45
cHex, rt
43% (2 steps)
R. L. Snowden et al., Helv. Chim. Acta, 88, 3055 (2005)

5
Ph Ph 1) NIS (2.5 eq) 3) NaClO2, 2-methyl-2-butene
MeCN-H2O NaH2PO4, t-BuOH-H2O
O O
0 °C, 62% rt, 92% I
O O
2) DDQ 4) CAN, MeCN-H2O, rt;
MeCN-H2O K2CO3, rt, 80% O
60 °C, 58%

Y. Kita et al., Angew. Chem. Int. Ed., 44, 734 (2005)

 Fukuyama Group - Group Meeting Problems
04/05/2006

1 Li
1)
O2N SO2Ph
Pd2(dba)3·CHCl3 1) K2CO3, MeOH CO2Me
Ph O O Ph Ph3P, THF, rt bicyclic 50 °C, 91% OH
compound
O O 2) SnCl2·2H2O (except for Ph) 2) Mo(CO)6, B(OH)3
CH3CN, rt CH3CN-MeOH-H2O
C19H16O4 94% (2 steps) C12H11NO3S reflux, 84%

Trost, B. M. et al., J. Am. Chem. Soc., 114, 8745 (1992)

2 Br OTIPS

OiPr Ph
cat. Pd(PPh3)4 O
cat. CuI PhCHO W(CO)6 (100 mol %)
NH2 MS5A Et3N, hν
Et3N N
DMF toluene toluene;
H3O+
87%
84%
84%
N. Iwasawa et al., Org. Lett., 8, 895 (2006)
3 1) KH (2.1 eq), THF;
4) Cl3CCOCl
Cl2C=CHCl
–50 °C to rt, 4 h Zn(Cu), Et2O
Me 79% rt, 1 h Me
C7H11O
Ar OH 2) n-BuLi (2.6 eq) 5) H2NOSO2Mes Ar O
THF, –90 °C; (except for Ar) CH2Cl2
iPr Allyl iodide rt, 16 h; Cl NH
HMPA basic Al2O3, MeOH Cl
Ar = iPr –40 to 0 °C, 2 h 72% (4 steps) O
3) H2, Pd/BaSO4
iPr ethylenediamine
DMF, 0 °C, 9 h
P. Delair et al., J. Org. Chem. 70, 8352 (2005)
4

TMSCHN2 H
Ni(COD)2 (10 mol%)
Tos N
Tos N THF, 60 ºC
TMS
68%

J. Montgomery et al., J. Am. Chem. Soc., 128, 2609 (2006)

5
OH

TsN3, CuI (cat.) PdCl2(PhCN)2 (cat.) Ts

N
Ph Ph
Et3N, CHCl3 dichloroethane O
rt, 12 h rt, 4 h

82% 99%

S. Chang et al., Org. Lett., 8, 1347 (2006)

 Fukuyama Group - Group Meeting Problems
04/12/2006

1 3) t-BuOCl; N
1) LDA, THF DBU
H
N –78 to 0 °C CH2Cl2, 0 °C
MeO N Et
Ac 2) NaOMe 4) NaBH3CN
MeO2C MeO N O
MeOH, rt TFA-MeOH, rt H H
Et CO2Me

H. Rapoport et al., J. Org. Chem., 109, 1603 (1987)

2
H COCO2Me
PhCHO MeO2C CO2Me
NOH bicyclic N CO2Me
compound
NH neat CH2Cl2 N Ph
80 °C, 16h (except Ph)
rt, 18h
Me Me
80% 60%

Heaney, F. et al. Org. Biomol. Chem., 3, 4351 (2005)

3
1) TFA
CO2Et CH2Cl2
EtO 1) Boc2O 92% NMe
CO2Et NaH, DMAP 2) MeI H
NH2 K2CO3 98% 97% NMe
tricyclic
EtOH compound
2) hν, Corex 3) MeNH2 O
EtOH, 97% toluene, 50 °C H
94% CO2Et
92%

J. D. White et al., Org. Lett., 8, 1081 (2006)

4 O
OMe OMe Br Br OMe OMe

OMe OMe
Br Br NaBH4 Indium powder
C27H26BrNO4
DCE EtOH EtOH
Br 50 °C, 1 h sat. NH4Cl aq. Br
N N
reflux, 3.5 h H H
OH
57% (3 steps)
P. S. Baran et al., J. Am. Chem. Soc., 128, 3908 (2006)
5
TESO Pd(PPh3)4 O
KHMDS, HMPA CO (800 psi) TESO
O O
R THF, –78 °C; CSA i-PrNEt
R
O comins' reagent MeOH/THF PhCN O
rt 65 to 110 °C
OTES
93% (from E)
77% (E/Z = 1.3:1) 92% (from Z) 56% from E
46% from Z
R = (E)-MeCH=CH(CH2)5-
J. L. Leighton et al., Org. Lett., 2, 2905 (2000)
 Fukuyama Group - Group Meeting Problems
04/18/2006

1
nBu
O
Bu
MeLi; MeLi; carbene CHO
Cr(CO)6 complex
MeOTf Br dioxane, 100 °C;
HCl

W. Herndon et al., Tetrahedron Lett., 46, 5117 (2005)

2 OMe
1) Ti(OiPr)4
EtMgBr (2 eq) MeO Br AIBN H
CO2Me 95% TiCl4 nBu SnH O
3

2) TMSOTf 71% 99%

2,6-lutidine H
OMe
88%

J. K. Cha et al., Org. Lett., 4, 3707 (2002)

3
TIPSO
TIPSO O O MsN3 Rh2Oct4 CO2Me
i- Pr2NEt DMAD, benzene, 95ºC; HN CO2Me
N OAllyl
MeCN Me Me O
N O N
O H CO2Allyl
96%
66%

S. L. Schreiber et al., Org. Lett., 8, 2063 (2006)

4
OBn
mCPBA, Na2CO3 O
MgBr NaH SnCl2* CH2Cl2, –15 to 0 °C, 7.5 h ;
HO
THF THF CHCl3 Ti(Oi-Pr)4, CH2Cl2
OBn 0 °C reflux 18 °C reflux, 1 h, 82%
O 1h 3h 1h
* Lewis acid
70% 90%
97%
M. G. Banwell et al., Synlett, 897 (1998)

5
OH PhI(OCOCF3)2 (1 eq) O
(CF3)2CHOH, 0 °C; O
O
NaBH4, rt;
aq HCl, 0 °C

63%

Y. Kita et al., Heterocycles, 66, 309 (2005)

 Fukuyama Group - Group Meeting Problems
04/26/2006

1
NNHTris OMe
n-BuLi (2.2 eq) 1) NBS, CH2Cl2
TMEDA, Hex, 0 °C; 0 °C, 95% OHC O
OMe 2) DBU, DMSO H
O O 95 °C, 90%
OTBS O O
CHO

85%
Y. Q. Tu et al., Org. Lett., 8, 1823 (2006)
2 Ph
Ph PhSeSePh H2O2, Py
toluene, rt, 5 h; TfOH SePh
Ph AIBN
• C29H24OSe
benzene rt to 80 ºC, 12 h; CH2Cl2
Ph
reflux, 10 h aq. Na2SO3 (sat.) rt, 1.5 h
Ph
92% 55% 94%
M. Shi et al., J. Org. Chem., 71, 1920 (2006)
3
O
Cl 1) ZnCl2, MeOH 3) PhN S NPh N
A
O S
2) NaN3, MeOH benzene C3ClNO
Cl reflux
OH CN

H. W. Moore et al., Heterocycles., 20, 1503 (1983)

4 O
H POCl3
N i-PrNH2 KOH
OHC OMe
A
CH2Cl2 THF-H2O
–30 °C rt; evaporation C10H8NO3K

86% 100%
C11H13NO4 OMe
A
CHO Me2NH·HCl 1 M HCl NH2

toluene THF O
rt rt

81% 95%
Zhu, J. et al., J. Am. Chem. Soc., 127, 6926 (2005)
5 MeO O
CHO
H CHO
1. t-BuLi, -78 °C; TMS BF3•OEt2, MgSO4. -55 °C H H
2. PPTS, MeOH TIPSO O

I
CHO
72% (2 steps) 79% OTIPS
TMS

Overman, L., J. Am. Chem. Soc., 2001, 123, 9033

 Fukuyama Group - Group Meeting Problems
05/09/2006

1 1) K, NH3, MeI
O OMe
t-BuOH (1 eq) 3) I2, THF-H2O
THF, –78 °C, 95% Me
rt, 90%
N O
O CO2Me
2) 6 N HCl 4) MeOH, n-BuLi H
OMe MeOH, rt, 95% THF, –78 °C, 87%

A. G. Schultz et al., J. Org. Chem. 69, 7728 (2004)

2 EtO2C Cbz
H
N
Cbz N
NH2NHCSNH2 SmI2 O
H CO2Me
AcOH THF-MeOH HN NH NH2
70 °C, 23 h rt

MeO2C O 87-95% 75-87% S

L. E. Overman et al. J. Am. Chem. Soc. 119, 7159 (1997)

3 O
CN Ph O
N O
C6H13CHO N
Bn O
O N O C4H9 N
+ CSA (cat.) NEt3 CO2C6F5 Ph O
C4H9NH2 toluene rt 15 min C6H13 N
30 min; 60 °C;
30 min; 110°C O
110°C; Ph

Jieping Zhu et al.Angew Chem. 114, 4467 (2002)

4
+ –
1) NaOH, RMe3N Cl
nC H CHCl3-H2O, 80 °C, 58%
11 23 2) conc.HCl-MeOH, rt, 89% nC H
O HO 11 23
O 3) K2CO3, MeOH, rt, 77% O
4) NaBH4, MeOH, rt, 84%
(R = C16H33)

Masaki, Y. et al., Chem. Pharm. Bull., 52, 848 (2004)

5
Boc CO2Me
i-PrO2S N Bicyclic compound
C16H26ClNO5S N CO2Me
a) HO(CH2)2I, Bu3SnH c) O3 then Me2S Boc
Et3B cat., O2 cat. 82% d) 4-AcNH-TEMPO cat, Br2 6eq
(±)
( + radical rearrangement) KOH (pH=11,5) Na2S2O5 10eq α-isokainic acid
b) n-BuLi 2 eq., C2Cl6 3 eq. 86% 0°C to 95°C (± protected)
e) TMSCHN2 - 72% (3 steps)

D. M. Hodgson et al, Synlett 8, 1267 (2005)

 Fukuyama Group - Group Meeting Problems
05/24/2006

1
H Ph H
N NNHTs N O
Cl
1) NaBH4
NaH; N3
O 1) Et3N, CH2Cl2, 50% THF, 93%

THF 2) CuOTf (1 mol %) 2) TFA

N N N
Boc CH2Cl2, 85% CH2Cl2, 90% H H
68%

Y. Qin et al., Org. Lett. 8, 2187 (2006)

2
MeLi S O
OTMS THF PhI(OAc)2 1)
0 °C; I2 TBAF Cl OPh
bicyclic O
OTBS compound CH2Cl2 THF
O 2) n-Bu3SnH Me
Me AIBN
TMS 53%
BF3•OEt2 Benzene
(2 steps) 85% (2 steps)
–78 °C

G. H. Posner et al., Org. Lett. 7, 4301 (2005)

3
n-C9H19Li 30% aq.H2O2 O
n-C6H13
; aqHCl 6N aq.NaOH H2NNHTs
MeO O n-C9H19
ether MeOH CH2Cl2-AcOH (2:1)
0°C to rt, 3h n-C6H13
rt, 1h 24h, rt

64% 67% 83%

Eun Lee et al. Bull. of Korean Chem.Soc., 5, 223 (1984)

4
Ph
AcO Ph
PtCl2 (10 mol%)
O
O PhMe (0.1M)
CO2Et OAc
100 °C, 6 h H CO Et
2

73 %

R. Sarpong et al., J. Am. Chem. Soc., 128, 6786 (2006)

5
TfOH (2.2 eq), CH2Cl2 TBAF CO2Et
SiPh3 0 °C, 1 h; toluene H2O2 Me OH
EtO2C
sorbyl alcohol, Py reflux, 6 h DMF OH
0 °C, 2.5 h 55 °C, 4 h

43% (3 steps)

S. M. Sieburth et al., J. Org. Chem., 64, 1781 (1999)

 Fukuyama Group - Group Meeting Problems
06/06/2006
1 1) Br2, CH2Cl2
–78 °C, 95%
PhS A
2) NaOH, EtOH C9H9BrS
0 °C, 91%

OTMS O
BuLi; HCl

A, cat. Pd(PPh3)4 Et2O, rt

85% 91%
T. Cohen et al., Org. Lett. 8, 2087 (2006)

2
K2CO3 CO2Me
O Pd(PPh3)4
I CF3 OCO2Me CO2Me DMF,100 ºC O
F3C
73%
Y. Lisag et al., J. Org. Chem. 70, 6980 (2005)
3
OPh
1) Br
O 1) DIBAL
CH2Cl2, –78 °C HO
Me i-Pr2NEt, MeCN OH
80% toluene tricyclic 87%
H N
compound Me O
H2N 2) PMBNH2
2) mCPBA, Na2HPO4 200 °C
OH H2, Pd/C, EtOAc; N
CH2Cl2, –78 °C (sealed tube)
(p-NO2C6H4O)2CO PMB
84%
78% 81%

R. M. Williams et al., Angew. Chem. Int. Ed. 43, 2930 (2004)

4
i-Pr i-Pr
O
MeO B N N
O
i-Pr i-Pr
[RhCl(C2H4)2]2 (3mol%)
dppf (6mol%) (10mol%)
Et3N, H2O Ni(cod)2 (5mol%)
OBn
dioxane, 100ºC toluene, 70ºC OBn
OBn
OBn
81% 90%
M. Murakami et al., J. Am. Chem. Soc. 128, 2516 (2006)
5 CHO
SiMe2Ph OMe
I 1) ZnI2, EtOH
+ 60 °C, 82% OBn
HN OBn
DBS 2) Pd(OCOCF3)2(PPh3)2 (10 mol%)
DBS N
OMe PMP, toluene, 120 °C
60%

DBS = PMP = 1,2,2,6,6-pentamethylpiperidine

L. E. Overman et al., J. Am. Chem. Soc. 115, 11028 (1993)

 Fukuyama Group - Group Meeting Problems
06/14/2006
CN
1
Hg(NO3)2, N
CH2Cl2 H NH
–40 ºC to rt, 2 h; HCl
H
NaBH4, MeOH reflux N
39% 53%

H. Heathcock et al., J. Org. Chem., 58, 564 (1993)

2
1. Zn, AcOH O
O 100 ºC
65% N
O N O
2. DAIB
KOH, MeOH HO
76%
O MeO OMe

W. Z. Li et al., Org. Lett., 5, 2931 (2003)

3
O
O Me
1. Eu(FOD)3 (10 mol%), 80 °C 3. LiDBB, THF Me
A
2. hν 4. PDC H
C14H20O Me
Me
32% overall yield

Rawal, V. H., et al., Org. Lett., 2, 2711 (2000)

4
• Ph Pr Pr
Ni(cod)2 (10 mol%) Ni(cod)2 (10 mol%) O Ph
O PMe2Ph (20 mol%) P(4-CF3-C6H4)3 (20 mol%)
C15H17NO2 EtO CN
EtO CN CH3CN, 80 °C, 8 h
toluene, 50 °C, 5 h Pr
Pr
77% 81%

T. Hiyama et al., J. Am. Chem. Soc., 128, 7420 (2006)

5 O
OEt
O Ph O
t-BuLi (4 eq) O
n-Bu n-Bu
OEt
Br Br THF –78 °C;
–78 to 0 °C 3% HCl-EtOH
reflux Ph

89%

Shindo, M. et al., J. Am. Chem. Soc., 121, 6507 (1999)

 Fukuyama Group - Group Meeting Problems
06/28/2006
MeLi
1 Et2O; PhCHO, Et3N, TMSCl
Cr(CO)6 A
MeI Et2O
Ph
Me OTMS A* O O
Me
Me OMe THF
MeO Me
90 °C
Ph
71%
*theoretical ammount: 2.0 eq J. Barluenga et al., Org. Lett., 8, 2703 (2006)
2
TMS
O CyCo(CO)2
+ O
H
neat TMS
TMS reflux H
45% N
N TMS OMe
OMe

K. P. C. Vollhardt et al., J. Am. Chem. Soc., 98, 6755 (1976)

3
SESNSO
CrO3 BF3·OEt2 O
SES
SnCl4 py. Cl(CH2)2Cl, 42 °C;
HN O H
O CHO MeNO2 CH2Cl2 NaBH3CN
rt 0 °C to rt t-AmOH, 0 °C
O
53% 80% 80%

SES = 2-(trimethylsilyl)ethanesulfonyl

S. M. Weinreb et al. J. Am. Chem. Soc. 112, 3475 (1990)

4 OH

1) toluene 3) BnNHCH2CO2H
65 °C, 2 d toluene, reflux, 12 h BnN
NH2
56% A 68%
+
C13H13NO2
2) MnO2, CH2Cl2 4) LiBH4 OH
O 25 °C, 12 h THF/MeOH, reflux, 6 d N
O H
96% 67%

O
O
B. B. Snider et al., Tetrahedron Lett., 40, 3339 (1999)

5 1) t-BuLi,THF, -40°C,
then allyl bromide, SCy
O- S
then CeCl3 10%, r.t. 3) P4S10, CH2Cl2,r.t.,90% I
S+ C13H23NO2S
Cy NMe2 O O
2) Dimethyldioxirane 4)I2, THF/H2O, r.t., 98%
69% over 2 steps

P. Metzner et al, Eur. J. Org. Chem., 1934 (2006)

 Fukuyama Group - Group Meeting Problems
07/04/2006
1 O 1) BocN=PPh3, THF, reflux
A
EtO2C CO2Et 2) m-ClC6H4CO3Li
CH2Cl2, 50% (2 steps)

1) A, CH2Cl2
n-HexS –78 °C to rt, 72%, 95% ee NH2

Me CO2Me 2) P(OEt)3, NEt3, CH2Cl2 Me CO2H

reflux, CH2Cl2, 36%
3) 6N HCl aq., reflux, 94%
A. Armstrong et al., J. Org. Chem., 71, 4028. (2006)
A. Armstrong et al., Chem. Commun. 904. (2002)
2 1) Tf2O, Py;
phenylalaninol, 87%
NaN3 PhCH2CN
2) PCC (2.2 eq)
CH2Cl2, 36%

X.-S, Ye et al., Org. Lett., 8, 1007 (2006)

3 O N N NMe2

N
Ph NO2 O N N NMe2
HCl aq. (cat.) oxazole O
N intermediate N
xylene rt, 96 h NH
O
155 °C, 72 h O
(sealed tube) 67% O Ph

29%
R. Nesi et al., J. Org. Chem., 61, 7933 (1996)
O
P Cl
O
4 Et3N, toluene;
filtration; O
O
P
HO EtO2CCHN2, O
ClFeTPP (1 mol%) CO2Et
40 to 110 °C
ClFeTPP = 5,10,15,20-tetraphenyl-
21H,23H-porphine iron(III) chloride
A. K. Mapp et al., J. Am. Chem. Soc., 128, 4576 (2006)

5
CO2H Red-Al
Ph OH O 1) LDA, THF, 0 °C; toluene
EtI, –78 to 0 °C; –78 °C to rt; O
bicyclic
OH
H2N toluene compound 2) LDA, THF, 0 °C; Bu4NH2PO4 Et
reflux Br EtOH-H2O
reflux
74% –78 to –30 °C
77%
74% (2 steps)

A. I. Meyers et al., J. Org. Chem., 51, 1541 (1986)

 Fukuyama Group - Group Meeting Problems
Li
07/11/2006
O
1)
1
THF, –78 °C
92%
1) PCl5, 2,6-lutidine 2) VO(acac)2, t-BuOOH
i-Pr
Et2O, rt CH2Cl2
77% 71% Me O
Me C10H18O
Me
i-Pr
2) DIBAL 3) Ac2O, Et3N, rt
N 4) benzene, reflux O
CH2Cl2, –78 °C
OH
83% 80% (2 steps)
P. Magnus et al., Tetrahedron Lett., 42, 4947 (2001)
2
MeO2C O
DMTSF
O LDA Cl CH3CN SMe
Me THF, –78 °C; MS 4A –40 °C;
N Me Me
OHC SMe N O
CH2Cl2 Et3N
t-Bu O SMe 68% O CO2Me
66%
DMTSF = [(Me)2SSMe]BF4

A. Padwa et al., J. Org. Chem., 67, 3412 (2002)

3
1) SH
O
O 1) hν (Pyrex filter) H
OH CH3CN, 100% O
C14H16O2S
Et3N, benzene 2) TFAA, TFA
88% CH2Cl2, 0 °C
2) mCPBA 89% Me
(theoretically 1.0 eq) 3) Raney Ni, EtOH
CH2Cl2, –78 °C 59%
72%

J. D. Winkler et al., J. Am. Chem. Soc., 128, 9040 (2006)

4 OH
OH
O CS2,NaH H
MeI 280 °C BH3-Me2S
O O
N
Cbz THF Ph2O, reflux THF, 0 °C;
45 min N O
–30 to 0 °C 30% H2O2, H
3N aq. NaOH Cbz
98% 89%
89%

Ogasawara, K. et al., Tetrahedron Lett., 42, 4523 (2001)

5 H
O N Ph
1) cat. Rh(OAc)2, toluene, reflux
OH
2) PhCN, TMSOTf, CH2Cl2
O 3) aq. HCl, THF O
N2 O
82% (2 steps)
O
B. L. Pagenkopf et al., Org. Lett., 5, 5099 (2003)
 Fukuyama Group - Group Meeting Problems
07/19/2006
3)
AcO OAc
1 I OAc
O
O 1) PhMgBr (2.1eq.) O
O S O O S
PR3 THF, –40 °C NH
N
S+ toluene 2) P(OMe)3 4) toluene
N3 O- MeOH, 60 °C reflux N
>90%
57% (4 steps)
K. Hemming et al., Tetrahedron Lett., 41, 10107 (2000)
2
1) Lithium acetylide R
2) TsCl, Py 1) PhCHO Ph
RCHO A PhNHOH
3) NaCN 2) A N CN
52%(3 steps) EtOH, 70 ºC H
68%(2 steps)

R= THPO(CH2)3

S. Blechert et al., Synlett, 717 (1994)

Br
3
Pd(OAc)2 (5 mol%)
P(p- tolyl)3 (25 mol%)
OH Cs2CO3
tBu
toluene, reflux

73% ( E/Z = 98/2 )

K. Oshima et al., J. Am. Chem. Soc., 128, 2210 (2006)

4 HO CuCl (10 mol%)

2-aminopyridine (10 mol%)
NaOMe (2.0 eq)

DME/MeOH O
N I N
100 to 150 °C
MOM MOM
92%, 95% de

S. Kobayashi et al., Angew. Chem. Int. Ed., 45, 2274 (2006)

5
O O
1) S MeLi, THF, –78 °C;
Cl Cl
HO Li
Et3N, CH2Cl2, rt SiMe2Ph
tricyclic PhMe2Si
compound
O 2) cat. BHT, EtOAc –78 to –20 °C; OH
120 °C (microwaves) HO
I MgCl
81% (2 steps)
THF, –78 °C to rt

61%

P. Metz et al., Angew. Chem. Int. Ed., 43, 5991 (2004)

 Fukuyama Group - Group Meeting Problems
08/02/2006
1 O
MgBr (1.0 eq) KH

THF THF O
H rt, 1 h rt, 2 h
O O
44% 42%

H. Heathcock et al., J. Org. Chem., 46, 9 (1981)

2
OH O
H
TBSO
TBSO OH 1. Co2(CO)8 A KOH
TBSO H
tricyclic MeOH
2. Me3NO, compound H
CH2Cl2, 30°C O
O
H H
B C

Brunell, D. J. et al., Org. Lett. 8, 3195 (2006)

3
Ph O O
Me O Ph
Me N ketene
+ Intermediate CO2Me
N O CCl4
80 °C Me Me 51%
CO2Me

J. Hegmann et al., Angew. Chem. Int. Ed., 27, 931 (1988)

4
O 1) CH2=CHMgBr, THF, −78 to 20 °C, 98%
O
2) TBHP, VO(acac)2, benzene/H2O, reflux, 74%
HO
3) SnBr4, CH2Cl2, 0 °C, 65%

C. M. Marson et al., Tetrahedron Lett., 44, 141 (2003)

5 S

O Cl

HO CO allyl
2
MeO OMe O
PhMe2Si CO2allyl OMe H O
1) (Me3Si)3SiH, cat. AIBN
pyridine PhH, reflux, 40% O
O OH H O
O CH2Cl2, rt 2) BF3·2AcOH, CH2Cl2, reflux
3) m-CPBA, KF, DMF, rt
99% >60% MeO OMe
OMe
*conversion yield

M. S. Sherburn et al., J. Am. Chem. Soc., 125, 12108 (2003)

 Fukuyama Group - Group Meeting Problems
08/09/2006
1)
Br
1 N
H
NaI, Hünig base N
EtO OEt DMSO, rt, 60% N
C24H28N2O3 H H H
NH 2) tert-butyl propiolate H2O-THF-AcOH
MeCN, 80 °C reflux H
(racemic) 3) H2O-THF-AcOH C19H20N2O O
rt, 39% (2 steps) 50%
P. S. Mariano et al. J. Am. Chem. Soc. 112, 7682 (1990)
2
1) Bu4NI∗, BBr3∗
CO2Me
PhSe Bu3SnH -30 °C
O CO2Me AIBN m-CPBA 2) CH2N2 CO2Me
C11H14O6
sunlump 95% CH2Cl2 75% (2 steps) MeO2C
300 W O O
O 50%
73%
∗theoretically 2 eq
P. Renaud et al., Helv. Chim. Acta. 85, 3965 (2002)

3
1) Et2Zn*, CH2I2* Ph
Me DME-CH2Cl2, 99%

OH Ph 2) DMP, CH2Cl2
40 °C, 79% OHC
Me
3) EtAlCl2, CH2Cl2
89% (cis/trans = 9/1)

*theoretically 1 eq
T. Rovis et al., Angew. Chem. Int. Ed. 44, 3264 (2005)

4
O 1) HONH2·HCl, NaOH 1) 3-chloro-2-cyclopentenone
EtOH-H2O, 80 °C Et3N, THF, 60 °C, 64% O
O A
Me NH
(C9H9NO2) O
O 2) LiAlH4, i-Pr2NH 2) Cs2CO3, 1,4-dioxane
THF, 60 °C 100 °C, 67%
77% (2 steps) O

D. Y. Gin et al. J. Am. Chem. Soc. 128, 10370 (2006)

5 1) t-BuLi (2.7 eq)

O O
THF-pentane, rt;
TMSCl (excess) OEt
O
OH Et3N
95% CsF (2.5 eq)
A MeCN
2) n-BuLi (1 eq)
Et2O C10H13F3O3SSi reflux
0 °C to rt; O
Tf2O 50% OEt
86%
Posner, G. H. J. Am. Chem. Soc. 107, 2571 (1985)
Kobayashi, H. et al. Chem. Lett. 1211 (1983)
Stoltz, B. M. et al. J. Am. Chem. Soc. 127, 5340 (2005)
 Fukuyama Group - Group Meeting Problems
09/06/2006
1
1) LDA, HMPA
1) Na2S2O3, H2O –78 °C to 0 °C
CO2Et C11H18O2S
2) 2) MeI CO2Et
Br
SMe
, Et3N

S. D. Larsen, J. Am. Chem. Soc., 110, 5932 (1988)

2 O Bu3SnMgCl
THF, –78 °C; K2CO3
OMe A
MsCl DMSO, 100 °C
OMe 96%
68%

A 1) (COOH)2, silicagel BOMO

BOMO n-BuLi KHMDS CH2Cl2

THF, –78 °C DME, 85 °C 2) H2O2, Ti(Oi-Pr)4 O

O
O i-Pr2NEt, Et2O, –30 °C
82% 90% O

W. C. Still et al., J. Am. Chem. Soc., 105, 625 (1983)

3 1) DMSO, (COCl)2
OH Et3N
CH2Cl2, –78 °C LDA 5% Pd/C, H2
N THF C6H13 N CO2t-Bu
2) Ph3PCH2 EtOH H
C6H13 CO2t-Bu –78 °C
THF, –78 °C
82% (2 steps) 83%
98%

P. Somfal et al., Tetrahedron. Lett., 36, 305 (1995)

4
S NH2 O
O Ph
Me Me NH2

benzene Me
Ph Ph Ph
reflux, 48 h

97% A. Kascheres et al., J. Org. Chem., 58, 1702 (1993)

5 Me
OH
H
OTIPS Me 1) TiCl(Oi-Pr)3, c-C5H9MgBr
H H
Me N THF (crude) O
PMP
O 2) SiO2*, CF3CH2OH*;
P(OEt)3, 68% H
OTIPS
*SiO2 and fluorocarbon solvents possess a high solubility of oxygen

J. K. Cha et al., J. Am. Chem. Soc., 123, 11322 (2001)

 Fukuyama Group - Group Meeting Problems
09/13/2006

OH
1 Me
CO2H
Ph
O O O
S Me NaOH aq.
N N N
H Δ
Ph OH
NO2 26 h

40%

2 D. E. Blackburn et al., J. Org. Chem., 34, 2799 (1969)

NH2 CO2Me
MeO2C Br
AuCl(PPh3) N H
Br Cs2CO3 TBAF AgOTf

N MeCN THF CH2Cl2 NH

TeocHN
Me rt, o.n. rt, 4 h reflux, 12 h N H
Me
45% 61% 89%

R. L. Funk et al., Org. Lett., 8, 3995 (2006)

3
Br
O 1) PhNEt2, toluene O
110 °C, 5 h, 66% N
N H
2) (CF3CH2O)2P(O)CH2CO2Me
O O KHMDS, 18-crown-6, 95% MeO2C
3) Pd(OAc)2, PPh3, K2CO3
CH3CN, reflux, 90%

R. L. Funk et al., Org. Lett., 8, 3689 (2006)

4
TBSOTf PCC O
ZnCl2 MeLi 2,6-lutidine MS4A TBSO
O
Dioxane - H2O THF CH2Cl2 CH2Cl2
OH reflux –78ºC 0ºC 25ºC

80% 85% 95% 82%

Z. Yang et al., J. Org. Chem., 71, 6892 (2006)

5
S O BF3•Et2O O O OH
p-Nitrobenzaldehyde
O N Ph O N
dry CH2Cl2, –40 °C HCl aq., 100 °C
93% 72% Ph SH NO2
Ph Me Me Ph

T. Kataoka et al., Chem. Eur. J., 12, 3896 (2006)

 Fukuyama Group - Group Meeting Problems
09/27/2006
O
1 1)
H
[ReBr(CO)3(thf)]2 (cat.)
Ph
MS4A
Ph
N toluene, 115 °C, 24 h

Ph Ph 2) H2SO4, AcOH

50% (2 steps)

2 K. Takai et al., J. Am. Chem. Soc., 128, 12376 (2006)

1) MVK
H2SO4 3) Pd/C, H2 Me O
O
rt, 77% MeOH
MeO2C Br
2) (MeO)2POCH2Li 4) t-BuOK, 18C6
THF, –78 ºC toluene, 80 ºC OMe
70% 64% (2 steps)

G. A. Kraus et al., J. Org. Chem., 56, 4147 (1991)

3
CF3
Cl
CDI
F3C
Cl MeCN N
OH 75 °C
Ph Ph
NHTr 84%

L. F. Frey et al., J. Am. Chem. Soc., 122, 1215 (2000)

4
1) CH2=CHCH2CH2CH2MgBr
THF,−78 to 0 °C, 36% SPh
Cl Ph (C3F7CO)2O
S 2) PCC, CH2Cl2, rt, 83% TsOH Cl
N
CHO N
3) NaIO4 (1.0 eq), MeOH-H2O toluene
Cl reflux
0 °C to rt, 85% Cl
67%

T. K. Sarkar et al., J. Org. Chem., 68, 6919 (2003)

5
S
NH2 1) BF4 N2 Ar 1) NaS Ar Ar
A H
Ar N
N Br N
2) C11H8ClN4•BF4 H
Br 2) O O
N H H
O
Br Ph O N O
Br Ar = 4-Cl-C6H4 3) CHCl3, Δ Ph
64% (2 steps) 85% (3 steps)

G. Hajós et al. J. Org. Chem., 68, 5652 (2003)

 Fukuyama Group - Group Meeting Problems
10/04/2006
1 Cl S2Cl2 N CN
HCl
Cl CN A O
CH2Cl2 toluene
(C2Cl3S2N, salt) reflux O
85%
59% (2 steps)
N CN
NH2 Ph3P (2 eq)
S
CO2H CH2Cl2 CH2Cl2
rt rt O

69% (2 steps)

Appel, R. et al. Chem. Ber. 118, 1632 (1985)

Besson, T. et al. J. Chem Soc., Perkin Trans. 1 2097 (1995)
2 O
1) hν, Pyrex filter 3) H2, Pd/C
MeCN MeOH
MeO2CN 73% (diastereomixture) 82%
MeO2CN
2) KHMDS, Comins' reagent 4) TsOH MeO2CO
THF, –78 °C EtOH, reflux
MeO2CO 64% 65% O
O O
J. D. Winkler et al., Org. Lett., 8, 4437 (2006)

3
Me Ph
Me 5 mol% Rh2(OAc)4
diallylsulfide S Me
Me
O N2 c-hexane
Ph rt O
83 %
T, R, Hoye et al., Tetrahedron Lett., 33, 169 (1992)
OMe OH
4
tol, reflux
OMe Ar
1) Li Ar
O THF, –78 °C 96% OMe

OMe 2) LAH, THF OMe OH

92% for 2 steps
OMe Ar
LDA, THF, 0 °C;
MeO

(Ar = ) 2 M aq. HCl

90% OMe
MeO
K. Suzuki et al., Tetrahedron Lett., 47, 6677 (2006)
5 1) Et2Zn, CH2I2
CH2Cl2, 0 °C;
O O benzaldehyde Ph
70% O
Me N N
2) NaH, CS2, THF, 0 °C; Me
MeO2C MeI O CO2Me
74%
3) n-Bu3SnH, AIBN
toluene, 80 °C
70% W. Lin et al., J. Org. Chem., 71, 8140 (2006)
 Fukuyama Group - Group Meeting Problems
10/11/2006

1
1) PbO2, t-BuNhNH2
CH3CO3H EtOAc H
NH2 Blue compound N
EtOAc 2) Li Naphtharenide
THF

E. J. Corey et al., Tatrahedron. Lett., 25, 491 (1984)

2 1) Dess-Martin
Me CO2Et periodinane CO2Et
1) TBAF HO2C CH2Cl2-H2O
TBSO THF, 0 ºC 40 ºC, 85% Me
DCC, DMAP
S H
AcO 2) MeMgBr 2) OEt
benzene
S CuI, LiBr 5 to 80 ºC Yb(fod)3
THF, –10 ºC Me
benzene O OEt
55% (4 steps) 80 ºC, 72%

C. Spino et al., Org. Lett., 8, 4385 (2006)

3
1) diazomethane* 4) BzCl, pyridine
Me 8 °C; rt bicyclic CH2Cl2, rt O
36% compound 49% Me
Ph Cl O
(expect Ph)
2) MeOH, KOH aq, rt 5) Et3N, MeOH; N
O 78% C12H12N2O PhCO2H, PhCO2Na Ph Ph
3) AcOH, rt reflux
75% 40%
*theoretically 3 equiv

J. Moore et al., J. Org. Chem., 50, 2141 (1985)

4
O COCl2, cat. DMF
Cbz-lle-OH O
Lawesson's rgt CH2Cl2-Toluene, 0ºC; H
N N
CH2Cl2, 0ºC to r.t. CbzHN N
Toluene, 90ºC DABCO, THF;
BnO2C NaN3, THF, O
90% 58% 86% BnO2C

H. Heimgartner et al., Helv. Chim. Acta, 89, 1841 (2006)

5
1) PPh3, THF, reflux; 3) toluene, reflux, 64%
O O p-MeOC6H4CHO, reflux; 4) K2CO3
H
mCPBA, –78 °C to rt MeOH, reflux
79% 88% MeO2C
HO HN
2) pTsOH•H2O 5) SmI2, THF
MeOH/H2O, reflux 64% HO
N3 H
70%
O O
J. D. White et al., Org. Lett., 3, 413 (2001)
 Fukuyama Group - Group Meeting Problems
10/18/2006

1 1) Cl CN 3) Cl CN
K2CO3, KI K2CO3, KI O
CO2Et acetone, rt acetone, reflux
87% 75% N
SH 2) NaH, EtOH, rt 4) NaH, dioxane
85% t-BuOH, reflux S NH2
26%

T. Hirota et al., Heterocycles, 55, 741 (2001)

2 O Me
CO2H aq. NaOCl *
NH
N Me 2 50 °C
N
H
*theoretically 2 eq

E. E. van Tamelen et al., Tetrahedron Lett., 12, 390 (1961)

3 O
H 185 °C; O
N CO2R NBS (1 eq.) CO2R Cl
Br MeCN, MS3A ;
N N
18-Crown-6, K2CO3; Br
Br N N
aq. NaHCO3, aq. NaCl N
H Br N H
N Br 93%
H
R = TMSE

Phil S. Baran and R. A. Shenvi, J. Am. Chem. Soc., 128, 14028 (2006)
4
HO NH2NH2 HO
t-BuOK/n-BuLi (2 eq);
LiBr H2O2, Cu(OAc)2

THF 68%
PhS –50 ºC to reflux

88%

T. Cohen et al., J. Am. Chem. Soc., 122, 412 (2000)

5
1) Na2WO4
30% aq H2O2, 76%
2) allylmagnesium bromide H
THF, 0 °C, 46% N
Me
N Me 3) Pd black, toluene
H reflux, 56% OH
4) Raney-Ni, H2
95%

S. Murahashi et al., J. Org. Chem., 55, 1744 (1990)

 Fukuyama Group - Group Meeting Problems
10/25/2006
O
1 1) S
NH2
Me 2) LiAlH(OtBu)3 4) mCPBA
Me O
Ti(OEt)4 THF, –78 to –50 ºC CH2Cl2, rt;
O O
CHCl3 3) mCPBA CH(OEt)3 EtO N Me
reflux CH2Cl2, –30 to 0 ºC p-TsOH Ts
69% 95%
35% (2 steps)
A. Padwa et al., J. Org. Chem., 71, 8591 (2006)
2
1) TFA
s-BuLi dioxane/H2O
LDA TMEDA rt, 48 h OH Ph
–78 °C, 20 min; tricyclic 80% Me
N –78 °C, 30 min;
compound HO2C NHt-Bu
PhCHO O (except Ph) 2) Pd(OH)2/C
O Cl 1h Ph
N Ph MeOH
61% (dr = 1.3 : 1); t-Bu
20 bar, 16 h
column H 60%
;
separation sat. NH4Cl aq.

71% S. Florio et al., Org. Lett., 8, 4803 (2006)

Br
3 TIPS TIPS
Ph CHBr3 MeLi Bu4NHSO4
Br
CH2Cl2-NaOH aq. ether toluene-NaOH aq. Ph
rt –78 to –50 °C; rt NTs
t-BuLi, –78 °C;
c-Hex
NTs 62%
c-Hex –78 °C

75% P. Wipf et al., Angew. Chem. Int. Ed., 45, 4172 (2006)

4 Me Me

N2 AuCl (10 mol%)

+
O O2C ClCH2CH2Cl
60 °C

Ph 74%
Ph O

N. Asao et al., Org. Lett., 8, 5361 (2006)

5
O 1. EVE, hυ, 0°C, 55%
EtO2C 2. DBU, benzene, reflux, 70% EtO CO2Et
O
N 3. DDQ, benzene, reflux, 65% Ph N CO2Me
Ph 4. NaOAc, MeOH, reflux, 80%
H

T. Sano et al., Chem. Pharm. Bull., 38, 3283 (1990)

 Fukuyama Group - Group Meeting Problems
11/08/2006

1 OMe

SH
(3.0 eq)
O O OMe NH2 S

toluene-AcOH
reflux, 6 h N
O H
59 %
O
O
A. Levai et al., Heterocycles, 68, 1319 (2006)
2 1) n-BuLi, tol, 0 °C;
OTf
TMS I
Ph , 70%
O
NHTs
2) AuCl (5 mol%)
TsHN
CH2Cl2, rt; SiO2, 61%

J. Cossy et al., Angew. Chem. Int. Ed., 45, 6726 (2006)

3 H
OH [CpRuCl(µ2-SiPr)2RuCpCl] (5 mol%)
NH4BF4 (10 mol%)
PtCl2 (10 mol%)
Me
ClCH2CH2Cl H
O
60 °C O
24 h
75 %

Y. Nishibayashi et al., J. Am. Chem. Soc. 126. 16066 (2004)

4 1) TiCl4 (2.2 eq) 3) cat. PdCl2 O

CH2Cl2 cat. CuCl, O2
TMSO –78 °C to rt DMF-H2O, 60 °C N
92% 84%
IR (cm-1): 1646
N3
O 2) PCC (1.8 eq) 1714 4) KOt-Bu (1.2 eq)
CH2Cl2, rt t-BuOH, 40 °C
88% 68% O

Y. Q. Tu et al., Org. Lett., 8, 5271 (2006)

5
3) [CpRu(MeCN)3]PF6 (10 mol%)
1) Na2S acetone-H2O
MeOH 60 °C O
92% 97% MeO2C
Et
Et
Br 2) mCPBA (2 eq) 4) DMAD
CH2Cl2 toluene MeO2C Pr
(2 eq) 85% 160 °C, microwave
2h
83%

Trost, B. M. et al. Chem. Asian J. 1, 469 (2006)

 Fukuyama Group - Group Meeting Problems
11/15/2006

1) thiourea
1 MeOH, rt
1) Hg(OAc)2 OAc
2) TsN=C=O (2 eq)
–5 to 25 ºC, 84% THF, rt
tricyclic
compound Ts N OAc
2) 1O2, TPP, hν 3) Pd2(dba)3•CHCl3 O
CH2Cl2, rt, 70% P(OiPr)3
THF, 80 ºC, 48% O

2
1) hν
benzene H H
O rt, 72%
O N
N O 2) benzene O
100 °C (sealed tube) O O
39%

S. M. Sieburth et al., J. Org. Chem, 65, 1972 (2000)

3
1) OTES
SMe 1) NCS, CCl4 CO2Et H O
2) PPh3, NaI, MeCN 1H
NMR H
KF, 18-C-6, MeCN
3) Eschenmoser's salt 5.38 (2H, d)
(2.0 eq) 2) TFA, CHCl3 H CO2Et
(basic workup)
J. P. Marino et al., J. Org. Chem, 52, 1 (1987)

4 n-BuLi (2eq.)
n-Bu Cp2ZrCl2
A
THF, –78ºC
n-Bu n-Bu
s-BuLi
O TMEDA TMS
+
C6H13
C6H13 TMS Et2O, –100ºC Warming to –30ºC C6H13
B C
72% (B:C=79:21)
R. J. Whitby et al., Tetrahedron Lett., 41, 5275 (2000)

5
(COCl)2 Oxone H
CH2Cl2, rt, 2 h; NaHCO3 NaOH O O
OH
TFAA (excess) CH3CN/aq. Na2EDTA H2O
O pyridine (excess) rt, 24 h reflux H
CH2Cl2, 0 °C to rt, 2 h
74% 75%
34%
D. Yang et al., J. Org. Chem., 68, 6321 (2003)
 Fukuyama Group - Group Meeting Problems
11/22/2006

1
HN
POCl3 (3 eq.)* C10H6ClNO CN
1H NMR peak
DMF (2 eq.)* NC CN CN
7.50-8.20 (m, 4H)
NHAc 80 °C 8.75 (s, 1H) 110-120 °C N N
80% 58%
10.55 (s, 1H)
* theoretical amount

P. J. Bhuyan et al., Synlett, 2593 (2006)

2 R (COCl)2, DMSO
HO CH2Cl2, –78 ºC; R
Et3N, –78 ºC to 0 ºC;
i-Pr
HO HN
MeNH2, 0 ºC to rt;
evaporation;
AcOH, 85 ºC

66%
R=
C. H. Heathcock et al., J. Org. Chem., 57, 2554 (1992)

3
O
1) K2PdBr4 (5 mol%) O
i-Pr O O2 (1 atm)
DME-H2O, 65 °C i-Pr
79% O
O
2) DBU
EtOAc, 50 °C O
O 95%

K. Goto et al., Chem. Lett., 1705 (1990)

4 Li
1) Hg(OAc)2 3)
AcOH
quant. O
–40 °C, 52%
O OH O O
2) 4) p-TsOH
CN MeOH-benzene
NaBH4 73% O
CH2Cl2-H2O
37%
T. Sugimura et al., Tetrahedron Lett., 34, 509 (1993)

5
1) H2O2 aq. 3) Br2 (3.3 eq), dioxane,
Me Me NaOH, MeOH, rt NaOH aq., 5 ºC; HCl aq. Me Me
62% 53%

O Me 2) TsNHNH2 (1.0eq) 4) Hg(CF3CO2)2 (cat) O O

EtOH, rt to 55 ºC CH2Cl2-H2O, rt
58% 93%

W. Dai et al., J. Org. Chem., 58, 1990 (1993)

 Fukuyama Group - Group Meeting Problems
12/06/2006

1
5% (t-Bu3P)AuCl KF (2 eq)
5% AgBF4 KHCO3 (4 eq)
PhOH (3 eq) H2O2 aq. (10 eq)
Ph2Si
H
CH2Cl2, rt, 12 h MeOH-THF (1 : 1), rt, 24 h OBn
OBn
O
79% 73%

F. D. Toste et al., J. Am. Chem. Soc., 128, 11364 (2006)

2
EtO2C
CO2Et CO2Et
Pd(PPh3)4 (5 mol %)
O O K2CO3
CO2Et +
OMe NMP, 80 °C OMe
OCO2Me (1.2 eq)
83% O
OH

Y.-M. Liang et al., Org. Lett., 8, 5777 (2006)

3
S i
H CO2 Pr
O N
H2NHN NH2 , citric acid (5 equiv.) S N
MeO2C
CO2iPr
EtOH, 100°C, 60h H
OMe HN OMe
O

L. Overman, et al., J. Org. Chem., 71, 9144 (2006)

4
Br O cat. AIBN
n-Bu3SnH O
O 6 M HCl
N C16H15NO2
Bn PhH reflux
reflux
70%
C16H14BrNO2 47%

P. Renaud et al., Helv. Chim. Acta, 80, 2148 (1997)

5
O mCPBA, CHCl3 O OH
H OAr
Me N 0-5 ºC, 1 h; Me O Ar
N Me N
EtOH, reflux, rt, 10h N
O N Cl O N
80% 82%
Me Me Me

K. C. Majumdar et al., Synthesis, 7, 1164 (2005)

 Fukuyama Group - Group Meeting Problems
12/12/2006
1 OH
OAc
TFA N
N O
10 min
rt N
OH H
N 61 %
H
S. Blechert et al., J. Am. Chem. Soc., 126. 3534 (2004)

2
OTBDPS OTBDPS
1) OEt (10 equiv)
LDA (10 equiv)
Me THF, –78 to –42 °C, 72% Me
O O O
H OMe H
2) n-Bu3N (xs)
OH OH xylene, 150 °C, 90% O O OH
n-Bu 3) citric acid (1.3 equiv) n-Bu
OH OH
MeOH, 75 °C, 100%
Me Me
T. F. Jamison et al., J. Am. Chem. Soc., 128, 15106 (2006)

3
1) Grubbs' gen-2 (5 mol%) 1) TMSCHN2 Boc
all-cis-polybutadiene (xs) CH2Cl2-MeOH N
OAc CH2Cl2, 40 °C, 64% rt, 91% O
diene Boc
Ph C17H20O2 2) BocNHOH*
2) LHMDS, HMPA, THF N
–78 °C; TBSCl, rt; Pr4NIO4*, CH2Cl2 HO
C13H14O2 aq. NH4Cl, rt, 68% 0 °C, 78% Ph CO2Me
dr = 1.7/1
(*theoretically 2 eq)

S. T. Diver et al., J. Am. Chem. Soc., 128, 15632 (2006)

4
1) m-CPBA (1 eq)
NH3, AgNO3 CH2Cl2-aq. NaHCO3 O
MeOH; 95% Ar S H
Ar S S Ar C8H8N2O2S
MeCHO, rt, 12h 2) methyl propiolate (15 eq) H CO2Me
97% 100 oC, 15 h
(Ar = 3-nitrophenyl)
71%

F. A. Davis et al., J. Am. Chem. Soc., 96, 5000 (1974)

5 1) MeLi (1 eq)
Me2O, –45 °C; D
CH2Cl2 (2 eq*) D
D SO2Cl
MeLi (2 eq*), LiCl, 29% CSI (1.1 eq) D
+ N
2) n-BuLi (2 eq) CH2Cl2 D O
N
ether; D –20 to 25 °C
ClO2S O
D2O

*Theoretical amount is 1 eq. 60% 20%

(Second step is just a proton-deuterium exchange.)

Katz, T. J. et al. J. Am. Chem. Soc. 1971, 93, 3782.

Katz, T. J.; Nicolaou, K. C. J. Am. Chem. Soc. 1974, 96, 1948.
 Fukuyama Group - Group Meeting Problems
12/26/2006

1
O
OH OTBS 1) MsCl,Et3N PIDA
TBAF O OBn
OBn CH2Cl2 AcOH CH2Cl2;

2) Me2Cu(CN)Li2 THF µW
Me Me OTs
OTBS THF, –78 to 0 ºC
OTs 95% 65% Me
88% (2 steps)

S. J. Danishefsky et al., J. Am. Chem. Soc., 128, 16440 (2006)

2
CHCl3
HC(OMe)3 aq NaOH
cat. TsOH BnEt3NCl t-BuOK (2eq)
O C15H24Cl2O
H MeOH, Δ O
CH2Cl2 THF, 0ºC H
58% (2steps) 43%

M. G. Banwell et al., Tetrahedron Lett., 47, 6817 (2006)

3 NH

Ph NH2
CO2Me MeO2C N Ph
Cl Et3N MeO2C

NH
CO2Me dioxane 170 °C, 8 h MeO2C
rt, 2 d O
84%
84%

A. de Meijere et al., Org. Lett., 4, 839 (2002)

4
CN
CHO
NaN3*
N
N Cl N
N DMSO, 80 °C
N3
* Theoretical amount is 2 eq.

J. Becher et al., J. Chem. Soc., Chem. Commun., 541 (1988)

5
Me3S(O)I* 1) PhSeCl, NaH OMe
OMe diethyl malonate H
piperidine, AcOH NaH THF, 0 °C to rt
CHO
CO2Et
EtOH, reflux DMF 2) NaIO4
MeO O
MeO OH THF/H2O H
97% O
79% 78% (2 steps)
* Theoretical amount is 2 eq.

S. Ohta et al., Org. Lett., 3, 1359 (2001)

 Fukuyama Group - Group Meeting Problems
01/09/2007

1 O EtO2C
N NaI (excess) O
N N
acetone, rt toluene, reflux N
Ph OEt
O Ph
60% 97%

M. J. S. Dewar et al., J. Org. Chem., 40, 1521 (1975)

2
SiH2t-Bu CO
CuCl, NaOt-Bu [Rh(acetone)2-
(P(OPh)3)2)]BF4 MeLi (2 eq) OH TBS OH
OH (R,R)-BDPP

Et2O, rt
n-Pr
n-Pr PhH, rt PhH, 60 ºC

95% (dr=4:1) 56% (2 steps)

J. L. Leighton et al., Org. Lett., 5, 3535 (2003)

3
O

H PtCl2 (3 mol%)

toluene O
reflux O
O
89%

G. Dyker et al., Chem. Commun., 2260 (2006)

4
MeO MeO
O O-
NaIO4 H
S+ CSA NaH MeOH-H2O; N
MeO N Et MeO O
CO2Me toluene THF heat MeO2C
reflux reflux
Br 90%
98% 99%

A. Padwa and M. D. Danca, Org. Lett., 4, 715 (2002)

5
N
1)
1) mCPBA CN
Me N CO2Me CH2Cl2 1) K2CO3 DMSO, 60 °C Me N CO2Me
quant. MeOH 93%
C15H14NO2Cl NC
Me 2) Ac2O, Δ 2) SOCl2 2) t-BuOK, HMPA Me
Ph 83% Py, 99% THF-DMSO N Ph
–30 °C

S. M. Weinreb et al., J. Org. Chem., 43, 125 (1978)

 Fukuyama Group - Group Meeting Problems
01/17/2007
1 Ph (1 eq)*
O Ph
Pb(OAc)4 (1 eq) H2NNH2•HCl
N NH2 A (C14H14N2)
CH2Cl2, rt, 30 min EtOH, 45 °C, 40 min
O 39-51% 75%

OEt
A (1 eq)* OEt
H PhH, reflux, 3 h
CH2Cl2, 0 °C, 2 h
(no purification) 37% (2 steps) (*theoretical amount)
O

A. Padwa et al., J. Am. Chem. Soc., 1993, 115, 2637

2
1) DIBAL (1.1 eq)
THF, –78 ºC;
1) mCPBA CHO
BrMg TMS CH2Cl2 H
62% 88%
C12H20O2Si O
O 2) TPAP, NMO (2 eq)* Ph2O 2) 70% HClO4 O
O CH2Cl2 reflux THF-H2O H
58% 70%
(*theoretical amount)
K. Inomata et al., Org. Lett., 2004, 6, 409

3
NH t-BuOCl (1.0 eq)
NEt3 (1.2 eq)

CDCl3, rt N
THF
Br N −78 °C to rt N
H Br
60% (2 steps)

T. Lindel et al., Org. Lett., 9, 283 (2007)

4
1) MeNO2, Et3N 3) PhNCO, Et3N
THF-EtOH 1,5-hexadiene (xs)
CHO rt, 85% PhH, reflux, 74% O
NC I
2) TMSCl, Et3N 4) ICl, CH2Cl2
THF, rt, 84% –78 °C, 53%

N. E. Schore and M. J. Kurth et al., J. Org. Chem., 1995, 60, 4196

1) Br2, CH2Cl2, 0 °C, 20 min

N N
2) KCN, THF-H2O (1:1), rt, 4 h
c-Hex 3) NaH, DMF, 40 °C, 6 h NC c-Hex
77% (3 steps)

N. De Kimpe et al., Tetrahedron Lett., 2001, 42, 3921

 Fukuyama Group - Group Meeting Problems
02/07/2007
1
TMSOTf, MeCN O
c-Hex OAc CH2Cl2, –78 ºC; c-Hex
OTIPS TfOH, –45 to 0 ºC
O O + N
TMS OH O
50%

T. Rovis et al., J. Am. Chem. Soc., 2006, 128, 16480.

2
1) methyl acetoacetate
NaH 4) pentafluorobenzoyl chloride
OAc Pd(PPh3)4 (cat) Et3N, Et2O
THF, 55 °C, 74% –78 °C to rt, 97%
C12H19NO Me
2) DMSO, H2O 5) Pd(OAc)2 (cat) N
180 °C, 99% P(p-tolyl)3 (cat) H
3) H2NOH⋅HCl, NaOAc Et3N, DMF, 110 °C, 54%
EtOH-H2O, 100 °C 6) KH
C11H16O2 97% 1,3-diaminopropane
65%
Fürstner, A. et al. Angew. Chem. Int. Ed. 44, 2777 (2005)
Fürstner, A. et al. Chem. Eur. J. 13, 1929 (2007)
3
R= 3)
PMBO
OTES
Me PhMe2Si
R
1) (MeO)3CMe (2.5 equiv) OH
O
OH EtCO2H BF3·OEt2 (1 equiv),
toluene CH2Cl2, MS 4A, –78 °C R
110 °C 48% (dr > 20:1)
O C12H18O3
O
O 2) DIBAL (1 equiv) 4) TBAF•3H2O (excess)
O
toluene DMF, 90 °C
–78 °C 85%
C10H16O3
81%
W. R. Roush et al., J. Am. Chem. Soc., 128, 15960 (2006)

4
1) MgBr
O 1) hv, hexane
THF 77% p-TsOH

2) CH2PPh3, DMSO benzene

OEt 2) HCl, H2O reflux
90% (2 steps) 70 °C, 77% 98%

M. C. Pirrung et al., J. Am. Chem. Soc., 103, 82 (1981)

5
O MeO
MeO N2 hν
O
THF
rt, 12 h H
H
72%
B. M. Stoltz et al., J. Am. Chem. Soc., 125, 13624 (2003)
 Fukuyama Group - Group Meeting Problems
02/14/2007

1
O
NO2BF4 N N
CO2Et
CH3CN O2NO
–16 °C CO2Et

17%

J. A. Murphy et al., Tetrahedron Lett., 36, 3039 (1995)

2
OMe
OMe LDA (2.2 eq) N
N
Cl THF Ph
Ph
–78 °C; rt Ph

76%

K. Oshima et al., Angew. Chem. Int. Ed. 42, 5613 (2003)

3 OMOM
I

NMe O
t-BuLi (2 eq.) TFA CSA Me
N
O
THF, –78ºC CH2Cl2 Toluene N
N 94%
Ts 0ºC to rt reflux Ts
95% 52%

S. J. Danishefsky et al., Angew. Chem. Int. Ed., 46, 1444 (2007)

4 condition
OTMS
A
OTMS
B

EtS O
B
EtS Hg(OCOCF3)2
O
HO CH2Cl2 HO
–40 ºC to rt
Me Me
54%

R. D. Bach et al., J. Am. Chem. Soc., 116, 9921 (1994)

 Fukuyama Group - Group Meeting Problems
02/28/2007

1 NO2
O CHO
hv
O
benzene
6h O2 N
O2 N
86%

D. Gravel et al., Can. J. Chem., 61, 400 (1983)

2
1) NBS, hv
Pd(OAc)2, K2CO3 CHCl3 NH H
P(2-furyl)3 H
58% Bicyclic hv, 350 nm
BrCH2SO2N Compound
DMF, MS4A 2) DBU acetone S
100 °C MeCN, heat O O
80% 52%
67%

L. A. Paquette et al., Org. Lett., 6, 1313 (2004)

3
OTBDPS 1) n-BuLi (1.1 eq) OTBDPS
THF, –78 °C Me2AlCl (1.1 eq)
Me Me
O O
2) Cl CH2Cl2
O SO2Ph –78 to 0 °C O
Me MgCl
91%
TIPS –78 to –10 °C TIPS Me
95%
A. B. Smith, III et al., J. Am. Chem. Soc., 123, 10942 (2001)

4
O
O 1) p-TsOH
CO2Me THF/H2O, rt n-Bu3SnH
hν 85% AIBN
CO2Me
hex/CH2Cl2, rt 2) (Imid)2C=S PhH, reflux
O DMAP
98% THF, reflux 92%
O 85% HO

M. T. Crimmins et al., J. Am. Chem. Soc., 120, 1747 (1998)

5
PhSAc + Cl2Nt-Bu A
benzene
reflux

A (1.5 eq)
OH DBU (2.0 eq) O

CH2Cl2
–78 °C

quant

T. Mukaiyama et al., Bull. Chem. Soc. Jpn., 75, 223 (2002)

 Fukuyama Group - Group Meeting Problems
03/07/2007
1
SO2Cl2
Cl I
O KSCN (1.5 eq) Cu(tfacac)2 Et3N
n-BuLi (1 eq) Et3N (5 mol%) CH2Cl2, 0 °C; HN
TrN H C26H25NS
THF CH2Cl2-MeOH benzene 1M HCl S
–78 °C to rt rt 100 °C THF, rt

40% (2 steps) 52% 65%

Njardarson, J. T. et al. J. Am. Chem. Soc. 129, 2768 (2007)

2 O
1) Et3N O
CH2Cl2, 25 °C
34%
+ O
O O
2) Cs2CO3 O
O
THF-H2O, 50 °C;
AcO OAc aq. HCl (acidify to pH 1) O
25 °C
57%
Snider, B. B. et al. Org. Lett. 9, 873 (2007)

3
O
Cl OH
Na (1 eq) hν O
N H
allyl alcohol MeCN
Cl
O Cl N
55% 59%
O
Booker-Milburn, K. et al. Org. Lett. 6, 1481 (2004)

4 2-norbornene (2 eq)
Br CO2Et

Pd(OAc)2 (10 mol%)

Me P(2-furyl)3 (20 mol%) EtO2C
Cs2CO3 Me
I
MeCN, reflux

90%
Lautens, M. et al. Angew. Chem. Int. Ed. 39, 1045 (2000)

5
O 1) conditions
A
2) Raney Nickel, MeOH, H2
C6H12O3

1) A
NaOAc, AcOH
rt to 70 °C
66% NBn2
NBn2
H2N OH N
2) Tf2O, 0 °C
29%
Gmeiner, P. et al. Heterocycles 53, 1371 (2000)
 Fukuyama Group - Group Meeting Problems
03/14/2007
N-hydroxysuccinimide
glyoxylic acid
1 TsNHNH2
DCC
A
aq. HCl dioxane
C6H5N3O4
81% 65% IR(CHCl3): 2100 cm-1

1) NaH 2) dirhodium(II) caprolactamate

HO A CH2Cl2, reflux, 89% MeO2C
Me Me
THF 3) LiOMe, THF-MeOH O
OMe 0 °C 0 °C, 76%
O 85% O OMe

House, H. O. et al. Org. Synth., Coll. Vol. V, 1973, 258.

Badet, B. et al. J. Org. Chem. 1993, 58, 1641.
Fuerst, D. E.; Stoltz, B. M.; Wood, J. L. Org. Lett. 2000, 2, 3521.
2 Me
Me
1) n-BuLi, THF-pentane, –78 oC
OSEM
O 97% 1) TBAF, DMF OSEM
allene O
Me 2) MsCl, i-Pr2NEt, CH2Cl2 2) AgNO3, acetone
O 95% (2 steps)
3) Pd2(dba)3, PPh3, 2,6-Lutidine O
TMSCH2CH2OH, CO, THF
70% (2 steps) O
J. A. Marshall et al., J. Org. Chem., 63, 5962 (1998)
3 CH2Cl2, –10 °C;
MeO2CCHO*, –78 °C; 1) NIS*
• * Me3SnSnMe3* CH2Cl2, –78 °C;
SnBu3 cat. [(π-allyl)2Pd2Cl2] cat. TFA O H
+ –78 to –40 °C; 77% O
C18H36O4Sn O O
Ts * C8H17CHO*, –78 °C 2) cat. [Pd(PPh3)4]
Ph N CO (100 atm) C8H17 H
B Br 54% K2CO3, MeCN, 70 °C
N 78%
Ph Ts
*1 equiv (theoretical amount)
C.-M. Yu et al., Angew. Chem. Int. Ed., 45, 1553 (2006)
4
OH
1) PhI(OAc)2 MeMgBr (2 eq) PhI(OAc)2
O
CF3CH2OH CuI (cat.) I2
CO2Me
2) NaHCO3 THF CH2Cl2 N H
–20 °C O
CO2H MeOH reflux AcO
60% Cbz
54% 80%
NHCbz

P. Wipf et al., J. Org. Chem., 64, 4576 (1999)

N N
5 N N
SO2

t-Bu
O O
Cs2CO3 PtCl2, tol, 80 °C;
MeO CHO MeO
THF-DMF Grubbs' gen-1
70 °C CH2Cl2

80% 64%
A. Fürstner et al., J. Am. Chem. Soc., 128, 6306 (2006)
 Fukuyama Group - Group Meeting Problems
04/04/2007
1
PivO
PivO
(EtO)3P O
s-Collidine
OH
PMBO p-Tolyl
O S O
MeO OH
O O ( as solvent) PMBO O
O 150ºC, 15h O
91%

A. Zakarian et al., Org. Lett., 7, 1629 (2005)

2 tBu tBu
SbF6
P NCMe
Au
O (5 mol%)
Ph
toluene
N 90 ºC, 1.5 h N
Me Me O
67%

A. M. Echavarren et al., Chem. Eur. J., 13, 1358 (2007)

3
Et
Oi-Pr (1 eq)*
N
K2CO3, Pd/C
NCbz Meldrum's acid (1.1 eq) C30H36N2O5
N
H H H
N
H H benzene MeOH
CHO 60 °C, 12 h rt, 20 min; H
Me
H2, 4 h MeO2C
C21H20N2O3 84%

* theoretical amount
L. F. Tietze et al., Angew. Chem. Int. Ed., 38, 2045 (1999)

4 1) acrylonitrile 1) aq. NaOH

t-BuOK THF-MeOH
t-BuOH reflux NHCO2Me
CO2Me 93% 70%
tricyclic
compound
2) PhMgBr 2) DPPA,Et3N O N
O THF, –78 ºC H Ph
toluene, reflux;
79% MeOH
3) MeSO3H, 0 ºC; 90%
H2O
92% F. Compernolle et al., Tetrahedron, 58, 4225 (2002)
5 LiTMP, CH2Br2 N2 TIPSO Me
THF, –78 °C;
n-BuLi (2 eq.) O A OTBS
Me –78 °C to rt; hν
OTBS A
OH
MeO2C TIPSCl, THF benzene
–78 to 0 °C, 52% 64%
Me Me Me Me

J. Org. Chem., 59, 4844 (1994) R. L. Danheiser et al., J. Org. Chem., 60, 8341 (1995)
 Fukuyama Group - Group Meeting Problems
04/10/2007
1
1) Tf2O, Na2CO3, 3) CH2=NMe2 I
CH2Cl2, r.t., 24h CHCl3, reflux, 36h
66% 98%
C10H16O
2) KOH, EtOH-H2O 4) mCPBA, -50ºC, 2h
O 140ºC, 72h 95% O
88% 5) DMSO, 140ºC, 4h
C10H16O 80% C11H16O

A. G. Martinez et al., Synthesis, 321 (1987)

A. G. Martinez et al., Tetrahedron: Asymmetry, 13, 17 (2002)
2
O
O 1) EtMgBr (2.5 eq)
THF, 25 ºC 3) SnCl4 (1.1 eq)
OH 2) PhCHO, cat. HCl CH2Cl2
O Ph
MgSO4, 25 ºC –78 to –23 ºC

72% (2 steps) 87%

L. E. Overman et al., J. Am. Chem. Soc., 1987, 109, 4748

3
30% AcOOH(1.05 eq.)
NaOAc(1.5 eq.) ZnBr2(0.1 mol%)

CH2Cl2 toluene CHO

0 °C to rt reflux

54% 59%

J. Altarejos et al., Tetrahedron, 61, 11192 (2005)

4
1) Me3NO
3(OC)Fe acetone, 56 ºC H
63%

O 2) ethylene
Grubbs' 2nd gen cat H
O
PhH, 50 to 80 ºC
74%

M. L. Snapper et al., J. Am. Chem. Soc., 2000, 122, 8071

5
1) i-AmONO
Ti(Oi-Pr)4 (cat) benzene, rt
O EtMgBr (2 eq) 68%
N R
MeO R Et2O, rt 2) MeOH O
R = n-C6H13 reflux
91%

O. G. Kulinkovich et al., Synthesis, 234 (1991)

O. G. Kulinkovich et al., Synlett, 3427 (2006)
 Fukuyama Group - Group Meeting Problems
04/18/2007
1
1) thiourea, NaI
EtOH, reflux; S
NH2CH2CH2NH2 3) Ac2O, pyridine H
Ar Ar O
C19H19NO4S
H H
Cl 2) PhCONHCH(OH)CO2H 4) PhCl, 150 °C O N
DCC, DMAP(cat.), DMF
Ar = PMP Ph

M.J. Melnick and S. M. Weinreb, J. Org. Chem., 53, 850 (1988)

2
1) CCl3COCl
Zn(Cu) 3) CeCl3, NaBH4 Ph
DME-CH2Cl2 MeOH 5) Ph
C10H8O
Ph 2) Zn 4) ClCO2Me DMSO
TMEDA, AcOH Et3N, DMAP Δ MeO2CO
EtOH CH2Cl2
20%(4 steps) 33%

F. L. Bideau et al., Synlett. , 800 (2007)

3 1) 2-cycloheptenone MeO2C
KHMDS
THF TBSO
O – 80 °C Pb(OAc)4
TBS O
2) KHMDS MeOH-benzene
TBS
18-crown-6 rt CHO
THF
– 80 °C; TBSO
Davis' oxaziridine

K. Takeda et al., J. Org. Chem., 72, 1379 (2007)

4
Ph3SnH
AIBN O
O

toluene
OTES reflux
OTES
3.5 h
39%
A. Nishida et al., Tetrahedron Lett., 36, 3015 (1995)
1) n-BuLi;
work up (acidic), 61%
O O
5 2)
N2
O
O TMS H , n-BuLi, 85%
+ NC
I
PPh3 3) O3; PPh3, 79%
4) KOH, THF-H2O, 99%
O

D. F. Taber et al., J. Org. Chem., 70, 8739 (2005)

 Fukuyama Group - Group Meeting Problems
05/02/2007
1 1) p-TsOH·H2O
RuCl3·nH2O
OMe MeNO2
70 °C, 90% NaIO4
tricyclic
O OMe compound HO2C CO2H
2) DIBAL, toluene MeCN-CCl4 O
O 0 °C
–78 °C, 100%
3) BF3·OEt2
MeCN, 0 °C, 99%
S. Nagumo et al., Tetrahedron Lett., 43, 5333 (2002)
2
H O
H2N
S NaNO2 (3 eq)* , HCl S
MeO
N
O MeOH
CO2H N O
H

* theoretical amount
R. J. Stoodley et al., Tetrahedron Lett., 10, 941 (1967)
3
1) vinyl magnesium bromide
Me 1) TMSC(Li)N2,THF Pd(PPh3)4, PhH, 70 °C Me
–78 °C to rt, 71% 88%
C11H17IO I
OHC O 2) Bu3SnCu(Bu)CNLi2 O
2) H2, CO, Rh(acac)(CO)2
Me THF, –78 °C; (S, R)-BINAPHOS Me Me Me
MeI, DMPU PhH, 30-35 °C, 20 atm
–78 °C to rt 3) CrCl2, CHI3, THF
3) I2, Et2O, 0 °C 72% (2 steps)
80% (2 steps)
E. N. Jacobsen et al., J. Am. Chem. Soc., 123, 10772 (2001)
4
thionyl chloride
(theoretically 1 eq)
CH2Cl2, MgBr
H Me
N –10 °C to rt; (1 eq)

filtration; THF toluene N

N reflux H
Me
96%
(as 4 eq) 51%
NH2

96%
Kim, Y. H. et al. Tetrahedron Lett. 26, 3821 (1995)
Julia, S. A. et al. Tetrahedron Lett. 27, 837 (1996)

5
1) MeLi (1.05 eq) Ot-Bu
1) benzene THF, –78 °C; THF, MW O
reflux, quant TFAA, 82% 120 °C;
t-BuO Ot-Bu C12H18O4 O
2) NBS, CCl4 2) Li DMP
OMe
C10H18O2 83% CH2Cl2, 0 °C
OMe
75%
, THF
37% (dr = 3:2)

F. Serratosa, Acc. Chem. Res., 16, 170 (1983)

D. C. Harrowven et al., Angew. Chem. Int. Ed., 46, 425 (2007)
 Fukuyama Group - Group Meeting Problems
05/12/2007
1
1) COOMe
N N
MeOOC MeOOC 105 ºC, 45h MeOOC OH

BocN S BocN S
2) Pb(OAc)4 (2.2 eq), benzene, reflux
3) NaOAc, MeOH

R. B. Woodward et al., J. Am. Chem. Soc., 88, 852 (1966)

2 1) t-BuOCl (1.2 equiv)

Me CH2Cl2, –78 °C; Me prenyl 9-BBN:
prenyl 9-BBN (2 equiv)
H –78 °C H
60%
H NC H NC
B
2) hυ, Et3N (xs)
PhH, rt
N 41% N
H (63% based on RSM) H

P. S. Baran et al., Nature, 446, 404 (2007)

1) allyl bromide
3 K2CO3, acetone 4) acrylonitrile, DABCO
reflux, 8 h, 92% H2O, rt
2) 180º C, decalin 3-5 days OCH3
5 h, 95% 67%
C8H8O3 H3CO
C12H14O3
isovanillin
3) MeI, K2CO3 5) Grubbs' 2nd gen. (5 mol%)
acetone, reflux 0.05 M CH2Cl2, rt CN
8 h, 83% 5-8 h, 90%

E. Wang et al., Tetrahedron, 63, 2824 (2007)

4 1) PhNTf2
NaHMDS
1) iBuO2CCl THF, –78 °C
Et3N, Et2O; 2) CH2=C(OEt)SnBu3 EtO H
OTBS CH2N2, Et2O Pd(PPh3)4, LiCl
O 0 °C to rt, 81% bicyclic THF, reflux
O
compound
O OH 2) Cu(CF3COCHCOCF3)2 3) methyl vinyl ketone
H H toluene, reflux HH
CH2Cl2, reflux, 96%
67% (3 steps) O OTBS

J. S. Clark et al., Angew. Chem. Int. Ed., 46, 437 (2007)

5
O
1) Mg 3) NH2NH2, KOH, HO OH H OH
Me Br(CH2)2Br, Br O HO(CH2)2OH H
MeO O 110 to 190 °C, 8 h O
THF, 1.5 h, 92%

2) TsOH, acetone, reflux 4) O3, EtOAc, –78 °C, 4 h;

nBu 11 h, 82% PPh3, overnight nBu
51% (2 steps)

D. Kim et al., J. Org. Chem., 65, 4846 (2000)

 Fukuyama Group - Group Meeting Problems
05/30/2007

1 O

H n-BuLi (1 eq) KH (1.3 eq)

Br n-BuLi (1 eq) cyclohexanone 18-crown-6
C11H18O
Ph3P CH3 −23 °C to rt THF, reflux
THF CHO
0 °C to rt;
56% 76%

E. J. Enholm et al., J. Org. Chem., 55, 324 (1990)

2 OMe
Ph
OMe
S OH TFAA 1) mCPBA (1 eq)
O (1.5 eq) 98% OHC O
+ C23H20O4S
O CH3CN 2) n-BuLi (5 eq) O
−40 ºC THF, −78 ºC;
O Me
DMF (5 eq) O
83% 56%
Me
Y. Kita et al., Org. Lett., 2, 2279 (2000)

3
O O
HO
BF3⋅OEt2, O2 tetracyclic compound H2, Pd/C
N3 N
–78 to 0 ºC C12H17NO3
THF
H H
40% 77%

F. G. West et al., Org. Lett., 9, 703 (2007)

4
O CO2Me
Me
CHO MeNHOH DMAD CO2Me
N
H
rt PhMe, reflux Me
O Me H
85% 50% O

S. Kanemasa et al., Chem. Lett., 797 (1984)

5
NOH

PhI(OAc)2 (1.5 eq) 1) conc. HCl S O

BzO O I2 (1.0 eq), hν dioxane, 40 °C Py, DMAP, O2 BzO
OH O
CN benzene 2) (COCl)2, cat. DMF toluene, 80 °C; OH
benzene P(OMe)3

S. Hatakeyama et al., J. Am. Chem. Soc., 116, 4081 (1994)

 Fukuyama Group - Group Meeting Problems
06/02/2007
1) MeLi, Et2O;
1 MeI;
pyrrolidine, Et2O 3) MsCl, Et3N,
86% 0 °C Including
Cr(CO)6
Cr
2) n-BuLi, –78 °C; 4) NaOH, EtOH
MeCHO, –78 °C 70% (3 steps)
1) LDA, THF MeO2C
–78 °C; Burgess rgt. (3 eq.) 4-NO2C6H4
NH
O
CHO THF
4-NO2 C6H4
74% 25%
A. Papagni et al., Eur. J. Org. Chem., 1149 (2001)

PPh3 (2.5 eq.) Cl

2 CCl4 (3.0 eq.)
O
Cl
O DBU (3.0 eq.)
NR2 = N
NH2 A
H N MeCN Cl
H Cl O
O (COCl)2, DMF (cat.) O
DCE, 40 min; ZnBr2 (cat.) N2
OH i-Pr2NH
R2N evaporation; R2N
EtO2C CH2Cl2 EtO2C
A, DCE, 2 h;
F CO2Et H2O, overnight 35 min F CO2Et

M. M. Bio, et al., Synthesis, 19 (2005)

3 Me
1) Ac2O
BrMg OBn
O Me Et3N, DMAP Me
(2 eq) CHO [Rh(CO)2Cl]2
CH2Cl2
Me (Cp)2TiCl2 LDA rt (0.5 mol%)
C25H36O Me
THF THF toluene H
CO2Me 2) NaCN Me
–40 °C to rt –78 °C DMSO 110 °C
Me Me 130 °C OBn
51% 81% 93%
51% (2 steps)
P. A. Wender et al., Org. Lett., 2, 2323 (2000)
4 1) LDA, HMPA
THF, −78 °C; Me
R O TMSCl, to 0 °C; 1) TBAF, THF 1) TBSCl, imidazole
HCl, H2O, 74% quant DMF, 97% H
R
OTIPS2) s-BuLi, PPh3CH3Br 2) Red-Al, Et2O 2) PPh3, Ag2CO3
THF, −78 °C to 0 °C
Me 0 °C; −78 °C Pd(OAc)2, 65 °C;
85% NIS, 97% TBAF, THF OH
R = (CH2)3CH(OCH2CH2O) 90 %
L. E. Overman et al., J. Am. Chem. Soc., 121, 5467 (1999)
5
1) LiOH, MeOH
2) i-BuO2CCl
1) SmI2 Et3N, Et2O; H
O
CHO MeOH-THF CH2N2
three O
CO2Et stereocenters
O 2) TBSCl, Im 3) Cu(CF3COCHCOCF3)2
DMF (5 mol%) H
CH2Cl2, reflux OTBS

J. S. Clark et al., Angew. Chem. Int. Ed., 46, 437 (2007)

 Fukuyama Group - Group Meeting Problems
06/06/2007

1
Bu
H 1) NCS, CH2Cl2, 0 °C
N
N
Bu 2) cat. CuCl, THF, 50 °C
58% (2 steps) Cl

R. Göttlich, Synthesis, 1561 (2000)

2 1) LAH
Et2O, 0 ºC
79%
Me
Me
1) KOt-Bu, 18-c-6 2) MsCl, Et3N
Me H O Me
HO THF, 0 ºC; MeI CH2Cl2
H 98% 79% M
tetracyclic e
compound MeO H Me
Me OMe 2) p-TsOH 3) KOt-Bu H
acetone/H2O, reflux t-BuOH, 40 ºC
Me
H 74% 84% Me
MeO

L. A. Paquette et al., J. Org. Chem., 64, 3244 (1999)

3
O
H
1)
O
H (C10H8O2)
SO2Ph
O
t-BuOLi, THF, –78 °C
O C18H10O4
2) DDQ, benzene, reflux 1,2-dichlorobenzene O
O reflux O
C17H10O3
83% for 3 steps
D. Mal et al., Chem. Commun., 1181 (1996)

4
1) 28% NH3 (aq.) 1) Jones reagent
dioxane acetone
OMe O
sealed tube 2) CH2N2, Et2O H
OMe CH2=S(O)Me2 120 ºC 0 ºC, 84%
C11H16O3
THF 2) HONO (aq.) 3) hυ
O
0 ºC 0 ºC to rt benzene, 96% MeO2C H
77% (2 steps) 4) DBU, THF
96% reflux, 96%

N-C. Chang et al., J. Org. Chem., 58, 4756 (1993)

 Fukuyama Group - Group Meeting Problems
06/09/2007
1 1) KCN (6.0 eq)
OMe Boc2O (3.0 eq) OMe
CH2Cl2-H2O TosMIC (1.0 eq) MeO
MeO tricyclic
15 h, 96% K2CO3 (1.0 eq)
N compound N
MeO 2) DIBAL MeOH C22H24N2O6 o-dichlorobenzene MeO
toluene reflux, 1 h; reflux, 20 h
–78 °C, 3 h KOH, reflux, 6 h
90% O
63%
C14H13NO3 82%

J. K. Cha et al., J. Am. Chem. Soc., 123, 3243 (2001)

2 1) NH2OH·HCl
O NaOH
EtOH-H2O
A XP =
(C6H10ClNO) N
2) Cl2, CH2Cl2 SO2
78% (2 steps)

NaHMDS
XP n-C7H15 THF, –78 °C; 1) NaBH3CN, MeOH
O O n-Bu n-C7H15
O A; 2) NaH, toluene, reflux; N
H
1N HCl aq. n-BuLi, CeCl3
–78 oC to rt
64% 59% (2 steps)
W. Oppolzer et al., Tetrahedron Lett., 35, 7015 (1994)

3 O
O
MeO S
Et Ac2O, TsOH
MeO N O CO2Me
toluene MeO
N
O 70% O
MeO
MeO2C
A. Padwa et al., J. Org. Chem., 61, 4888 (1996)

4 1) Ph3P, toluene
1) DMF, POCl3 reflux CO2Me
O CH2Cl2, 0 °C to rt monocyclic 94% (E/Z = 92/8) CO2Me
compound
Ph Me 2) NaN3, DMF, rt 2) DMAD, toluene
C9H7NO N Ph
3) hv (Pyrex filter) reflux, 55%
MeCN, rt

T. Nakata et al., Heterocycles, 48, 2551 (1998)

5
1) hexamethylenetetramine
CHCl3, rt 4) NaIO4 (1 eq)
O 2) conc. HCl, EtOH, rt MeOH-H2O, rt O
(acidic workup) 89% Cl
Cl Br
3) 2,5-dimethoxytetrahydrofuran 5) TFAA N
SMe NaOAc, AcOH, 100 °C DMF, 0 °C S
75% (3 steps) 42%
V. Nacci et al., J. Med. Chem., 41, 3763 (1998)
 Fukuyama Group - Group Meeting Problems
06/23/2007

1 1)
O

OEt MeO

Ba(OH)2 P(OEt)2
O MeO NH2
O wet THF MeO
rt, 86% 1) Ac2O, Et3N, CH2Cl2 TsOH (10 mol%)
C13H19NO2
H 2) LHMDS, toluene,
2) TFA toluene MeO N
N Et3SiH –78 to 80 oC reflux H O
Tr CH2Cl2 77% (2 steps)
3) DIBAL, toluene, NH
0 oC, 71%
–78 oC, 59%

N. A. Magomedov et al., J. Org. Chem. 72, 3808 (2007)

2 Pb(OAc)4 A
Me2C NNHCO2Me
MeOH C6H12N2O3
MeO
40-80% O
OMe
CO2H N
MeO
1) DPPA, TEA A*
MeO
2) toluene, reflux toluene, reflux *Theoretically: 2.0 eq
N N
Me Me
75%

J. Warkentin, Synthesis, 279 (1970)

James H. Rigby, Patrick J. Burke, Heterocycles, 67, 643 (2007)

3
6N NaOH (4.0 eq)
H LiTMP (1.0 eq)*, TMSCl (1.0 eq)* aq. H2O2 (3.0 eq), H
Me O Me O
THF, –78 to 0 ºC; MeOH, 0 ºC, 83%;
Me H Me OH
Pd(OAc)2 (0.5 eq), CH3CN Li, NH3, THF, –33 ºC, 63%;
TBSO aq. HF/CH3CN (5:95 v/v)
68% (2 steps) 86% O
O OH
* theoretical amount
S. J. Danishefsky et al., Angew. Chem. Int. Ed., 46, 2199 (2007)

4 1) SeO2, TBHP, CH2Cl2, 90%

2) NaH, AllylBr (theoretically 1 equiv)
OH THF, 73% O
O
3) DBU, toluene, 220 °C, 75%
4) TPAP, NMO (theoretically 1 equiv)
MS4A, CH2Cl2, 70%
L. Barriault et al., Org. Lett., 4, 1371 (2002)

5
1) Jones' reagent, acetone, 0 °C, 96%
2) SOCl2, CH2Cl2, 0 °C to rt; evaporation; Ph
CONEt2
PhNHCH(Me)CO2Me, toluene, 89% N Me
2
3) LiOH·H2O, THF-H2O, reflux, 99%
OTBS 4) DCC, CH2Cl2, 89% CONEt2

G. Bélanger et al., J. Org. Chem., 72, 1104 (2007)

 Fukuyama Group - Group Meeting Problems
07/04/2007

1
N2
O HO OTIPS
Br hν (vycor)
+ OTIPS Br
ClCH2CH2Cl
rt; reflux
Me
68% Me

R. L. Danheiser et al., J. Am. Chem. Soc., 116, 9471 (1994)

2 1) In (powder)
1) O
Me
O H
Bn Cl Br
N OMs
Et3N, CH2Cl2, 0 °C THF-aq. NH4Cl
C14H15NO3 O
O H H Me
2) PTSA 2) MsCl, Et3N H H
O
THF/H2O, Δ toluene N
3) NaIO4, NaHCO3 sealed tube O Bn
CH2Cl2 rt to 190 °C

43% (2 steps)
B. Alcaide et al., Eur. J. Org. Chem., 98 (2005)

3
OtBu
1) HCl, NaNO2 AcHN
Me2N NMe2 H2O, 0 ºC
O CO2Me C14H22N2O5
N CO2Me
Boc toluene, 100 ºC 2) H2, Pd/C O N
AcOH, Ac2O Boc
87% 35%, 86% de
(2 steps)

B. Stanovnik et al., Eur. J. Org. Chem., 1581 (1999)

4
O MgBr DMAP O
CuI IBX, NMO formalin HCl
O
THF DMSO THF CH2Cl2
–20 ºC to rt 70 ºC 50 ºC 0 ºC

85% 64% 63% 68%

C. M. Williams et al., Eur. J. Org. Chem., 3181 (2006)

5
1) Me2NCH(OMe)2
O dichloroethane, rt; O
O O
HO evaporation;
Ac2O, 100 ºC, 68% O
HO O O
2) LiHMDS, t-BuOOH
OH THF, 0 ºC, 77% OH
O O
B. Trost et al., J. Am. Chem. Soc., 121, 6131 (1999)
 Fukuyama Group - Group Meeting Problems
07/17/2007
s-BuLi
1 Ti(Oi-Pr)4, TMEDA
TMS A
THF, –78 to –40 °C
C6H14Si C18H41O4LiSiTi
OBn OBn
OBn OBn OH
1) A, THF, –78 °C 3) hν, THF, 77%
CHO tricyclic
compound
2) toluene, 100 °C 4) n-Bu4NOH
N3 80% (2 steps) DMF, –20 °C HN
OBn 49% OBn

M. A. Ciufolini et al., Angew. Chem. Int. Ed., 41, 4688 (2002)

2
1) PMBNH2
O CF3CH2OH PMB CO H
2
70 °C Et3N (excess) N
+ CN mixture of two
O
OMe 2) CSA, PhH diastereomers
OH THF-H2O (10:1)
CO2H 56% (2 steps) 70 °C OH
OMe
quant. single isomer

Y. Kobayashi et al., Synlett 1585 (2007)

3 1) Pd/C, H2
O O
MeOH, rt;
Cl Cl LAH,THF
NO2 Br Br 0 °C to reflux
(1 eq)
S 48%
Et Zn (2 eq)
C19H22N2O3 N N
NH toluene 2) AcOH
–78 °C to rt H
reflux rt Et
72% (*epimerization)
66%

A. Padwa et al., Org. Lett., 7, 2925 (2005)

Cr(CO)5
4 Me OMe
TMS OH O
dioxane
reflux; Me
evaporation;
O silica gel/CHCl3
Me Me
45%
L. Zhang and J. W. Herndon, Heterocycles, 67, 233 (2006)

5) KOH, MeOH
5 N2
1) copper (ll)∗ 60 °C; HCl;
I
tol, reflux 3) KHMDS, THF; NaHCO3, KI
91% CS2, MeI I2, THF-H2O O
O
AcO O OTBS
O 2) K2CO3 4) n-Bu3SnH, AIBN 6) TBSOTf
Me MeOH tol, 110 °C 2,6-lutidine Me
60% (3 steps) CH2Cl2, 0 °C to rt
77% (3 steps)
∗ bis-(N-t-butylsalicylaldiminato) copper
S. J. Danishefsky et al., J. Am. Chem. Soc., 129, 3498 (2007)
 Fukuyama Group - Group Meeting Problems
07/25/2007

1
O N
t-BuOK MeLi, Et2O, 0 °C to rt; R
CHBr3 O N R; R=
68% DDQ (aromatization)

40%
M. Lechner et al., Angew. Chem. Int. Ed., 14, 765 (1975)

2 1) (CH3)3SiCH(CH3)CO2Et
LDA, THF, –78 °C to reflux
1) LDA (2 eq), THF 2) NaOH, EtOH, reflux
–78 °C to reflux 75% (2 steps)
O C11H18O
2) CCl4, reflux 3) (COCl)2, benzene, rt to 55 °C
O O 72% (2 steps) 4) Et3N, toluene, reflux
O
31% (2 steps)
5) HI, benzene, 51%

B. B. Snider et al., J. Org. Chem., 53, 4508 (1988)

3
OMe OMe
4)
OTBS 1) MeN3, toluene · O
rt, 87% PPTS, rt, 63%
O C13H14N2O3 O
Ph N 2) hν, dioxane, 78% 5) hν, MeCN Ph N
3) AcOH-H2O-THF 47% (dr = 4 : 1)
NMe
55 °C, 67% O
O

P. Garner et al., J. Org. Chem., 54, 2041 (1989)

4
COMe
O
O O O glycine
+ +
toluene, reflux
O
72% COMe

L. T. Scott et al., J. Am. Chem. Soc., 119, 10963 (1997)

5 [Rh(nbd)dppp]PF6 (5 mol%)
BHT (10 mol%)
1) Cl3CCOCl (1 eq) O
Zn-Cu m-xylene, 135 °C
ether, reflux, 1 d 81%
C12H12O
2) Zn Ni(cod)2 (10 mol%)
H2O PCy3 (20 mol%)
AcOH, 80 °C, 1 d
(yield not reported) toluene, 100 °C O
89%

Murakami, M. et al. J. Am. Chem. Soc. 124, 13976 (2002)

Murakami, M. et al. Chem. Commun. 4599 (2006)
 Fukuyama Group - Group Meeting Problems
09/05/2007

1 DIBAL
propargylbromide
Bu4NHSO4 t-BuOK
O O
O O
O ether 50% NaOH aq t-BuOH
0 ºC rt reflux O
O
O H 43% 57% quant
H O
O

K. Kanematsu et al., Tetrahedron, 51, 3499 (1996)

2 O
O
1) toluene 3) MeOTf (1.0 eq)
110 ºC CDCl3
O O H
OBz 2) TBSCl, DMF 4) CsF in DMF O
imidazole CH2Cl2 (0.02 M), rt MeO
91% (2 steps) 89% OBz

P. A. Wender et al., Org. Lett., 9, 1829 (2007)

3 3) cat. Tf2NH
1) Et3N*, TMSOTf* allylSiMe3*
O O Me
Et2O, –20 °C to 0 °C CH2Cl2-liq. SO2
Me Me 97% –78 °C;
C21H22O3 Ph O O Ph
2) BzF*, TBAF* evaporation; Me
O
THF, rt, 90% Et3N*, TMSOTf*
MeOH, –78 to –50 °C Me
Ph Me
68%

*theoretical amount: 1 equiv

P. Vogel et al., Org. Lett., 6, 1053 (2004)

4
OH
1) mCPBA H O
O
2) Ac2O, Py, DMAP 3) TMP, DMSO, Δ O
H
81% (2steps) 26% O
O
O
O
D. Trauner et al., Org. Lett., 8, 5901 (2006)

5
1) Pd(PPh3)4 (5 mol%), PhI
CO (200 psi), CO2 (200 psi), Et3N O Me
HO Me
OBn 100 °C, 77%

2) BBr3, CH2Cl2, –78 °C O

O O Ph
3) o-NO2PhSeCN, P(n-Bu)3, THF O
4) H2O2, THF, 73% (3 steps)

K. C. Nicolaou et al., Angew. Chem. Int. Ed., 46, 4708 (2007)

 Fukuyama Group - Group Meeting Problems
09/11/2007
1 2.5 mol% [RhCl(C2H4)2]2
5 mol% (R)-BINAP Ar
MeO2C Me Me
ArB(OH)2
Me Me
MeO2C dioxane
100 ºC, 2 h MeO2C O

Ar = 3-ClC6H4 80%, 94% ee

M. Murakami et al., J. Am. Chem. Soc., 127, 1390 (2005)

2 O

O
O OH
NTs 1) MeMgBr, Et2O, 0 °C CN
2) MCPBA, CH2Cl2, 0 °C LiOtBu Me
O C14H17NO4S
3) CH(OMe)3, BF3⋅Et2O THF N
CH2Cl2 –60 °C to rt;
then air O CN
c.a. 86% (3 steps)
84%

Norbert D. Kimpe et al., Synlett, 741, (2007)

3
1) hν (500 W halogen lamp) 1) NaH, MeO2C CO2Me
Me NEt2 O
cyclohexane
reflux, 71% THF OMe Me
S S MeO
C9H13NO2
N O 2) hν (125 W Hg arc lamp) 2) TsOH, toluene NMe
TEMPO, toluene reflux, 73% (2 steps) MeO C
Me 2
rt, 83% 3) MeO
3) mCPBA, CH2Cl2, 84% , toluene
MeO 140 °C, 86%

R. S. Grainger et al., Angew. Chem. Int. Ed., 46, 5377 (2007)

4 MeO2C
HO Et O 1) O
H
MeS 2) DMTSF* O
MeO2C Cl MeCN, –40 ºC; 3) TsOH
NH Et O
MeS N
MS, CH2Cl2 Et3N THF MeS

71% 67% 72%

* Dimethyl(methylthio)sulfonium Me Me
tetrafluoroborate S S
Me BF4 A. Padwa et al., J. Org. Chem., 70, 5197 (2005)

O O OO
O (theoretically 2 eq) OH
O
Mn(OAc)3·2H2O (2 eq)
AcOH, 50 °C H
O
56%
M. Balci et al., J. Org. Chem., 72, 3353 (2007)
 Fukuyama Group - Group Meeting Problems
09/26/2007

1 1) MgBr
CuBr·Me2S,
LDA, THF, –78 °C; THF-Me2S
PhNO, –78 °C; H2O2, NaOH –40 °C to rt O
O
LiOH Et2O-H2O 2) 4.5 mol% HNTf2
CO2Me dioxane-H2O 0 °C to rt; DCE, 70 °C
30 °C H2SO4 (aq) 81% (2 steps)

75% 68%
H. Yamamoto et al., J. Am. Chem. Soc., 129, 9534 (2007)
2
OMs
OH
Silica gel Silica gel

CH2Cl2 CH2Cl2
O
O 40% CO2R 40% CO2Me
(R=t-Bu) (R=Me)

A. E. Nadany and J. E. Mckendrick, Tetrahedron Lett., 48, 4071 (2007)

3
t-BuOK (2 eq.)
THF 1) CH2N2, Et2O
O O HO OH
–78 to 40 ºC; NaOH (6 eq.) 0 ºC
CO2Me
Br2 (1 eq.) DMSO-H2O 2) NaBH4, MeOH
pentane O2 0 ºC
40 ºC 70 ºC 84% (2 steps)

67% 79%

A. Krief et al., Tetrahedron Lett., 43, 6167 (2002)

4
O

LDA SH
O O Me Me
THF, 0 ºC;
Me Ph C10H12N2 N
N N Ph
(PhO)2P(O)Cl, rt; Et2O, rt H
Me S
NaN3, DMF
72%
50%

H. Heimgartner et al., Helv. Chim. Acta, 75, 1866 (1992)

5 Cl

Br
1) Pd(PPh3)4 (5 mol%)
1) K2CO3 ZnEt2 (6 eq)
CH3CN 1) (COCl)2, DMSO Et2O-hexane
CN
CO2Me 98% Et3N, CH2Cl2, −78 °C ; I2, 91%
OTBS OTBS
BnHN 2) LiBH4 2) PH3P=CH2, THF 2) NaCN, DMSO N
MeOH-Et2O −78 to 0 °C 77% Bn
95% 85% (2 steps)
T. Cohen et al., Org Lett., 9. 3825 (2007)
 Fukuyama Group - Group Meeting Problems
10/03/2007
1 tBu
1) Si 3) PhMgBr, THF OH
tBu
0 °C to rt;
Me C6D6, reflux 3 N aq. HCl, 77% Ph OH
C27H56O3Si2 H Me
TIPSO 2) 4) CsF, CsOH·H2O HO
O2N NC
t-BuOOH, Et2O
CH2Cl2, rt; reflux, 88%
1 N aq. HCl, 57%

K. A. Woerpel et al., J. Am. Chem. Soc., 124, 6524 (2002)

2
1) CBr4, PPh3
Chloramine-T CH2Cl2 Ts
NBS (cat.) MgBr SnCl4 (1.0 eq) 0 °C to rt, 78% N

O OMe MeCN Et2O CH2Cl2 2) t-BuLi, THF

–30 °C to rt 0 °C to rt –78 to 0 °C
79% 56%
56% 32%

A. Armstrong et al., J. Org. Chem., 72, 8019 (2007)

3
N NH2
O O
4 N H2SO4
O C11H10N2O2 O
AcOH 100 °C
118 °C
O O
2 eq

M. E. Baumann et al., Helv. Chim. Acta., 67, 1897 (1984)

4
OMe
1) NH2NH2, DMF
80 oC
MeO2C CO2Me C17H14N2O3 2) TsCl, Py.
N N O
N tetracyclic N
H compound 3) Na2CO3 H
Me MeOH, rt
ethylene glycol CHO
170 oC, 10 min
quant
71% (3 steps)

V. S. Giri et al., Synth. Communications, 28, 9 (1998)

5
Br HS 1) KOt-Bu
EtOH (20 mM) 3) mCPBA CN
79% CH2Cl2, 76% 1,2-dichloromethane
+ C19H21N3O2 N
N 2) hν (Hg, 180 W) 4) Me2NCOCl relfux
P(OMe)3 CH2Cl2. rt; "not a pyridine"
64% TMSCN 54% (2 steps)
Br SH

Fürstner, A. et al., J. Am. Chem. Soc., 129, 12676 (2007)

 Fukuyama Group - Group Meeting Problems
10/09/2007
1) NH2OH•HCl 4) Ac2O, rt, 89%
NaOH 5) LAH
1F EtOH, reflux dioxane, reflux F
89% 91% N Et
C12H13FN2
N 6) CO2Me
N
2) PPA, 90 ºC ; H
H MeOH, rt, 75%
O H2O, 71% CO2Me
3) LAH
dioxane, reflux
65%
J. B. Hester, J. Org. Chem., 32, 3804 (1967)
Voskressensky L. G. et al., Tetrahedron, 62, 12392 (2006)
2
OTMS O
MeLi, THF, 0 ºC; PhI(OAc)2, I2 1) NaN3, DMSO, 24 h
C15H19IO2 NH OH
O CH2Cl2, 0 ºC 2) H2, Lindlar's catalyst
MeOH, 24 h Ph
Ph 62% (2 steps)
BF3• OEt2, –78 ºC syn-product 74%
30 min anti-product 71%

G. H. Posner et al., Org. Lett., 9, 2673 (2007)

3
O Cl
TIPSO
CHCl3
50% aq NaOH AgBF4, MeCN
C24H38Cl2O2Si
BnEt3NCl reflux Et
Et
OMe 81% (2 steps)
OMe
F. G. West et al., Org. Lett., 9, 3789 (2007)
4
1) trichloroacetyl chloride 3) n-BuLi (2.2 equiv)
THF, 0 °C to rt Et2O-hexane
97% –78 °C to rt;
morpholine C6H8Cl3NO A
(2.1 equiv) 2) PPh3 (1.1 equiv) TMSCl (1.2 equiv)
o-xylene, 150 °C –20 °C to rt
80% 75%

BF3•OEt2 (1.4 equiv)

A (1.4 equiv) KHF2 (5.0 equiv) O
O O
PhO
CH2Cl2, 0 °C; H2O, MeCN PhO
0 °C to rt

M. Movassaghi and E. N. Jacobsen, J. Am. Chem. Soc., 124, 2456 (2002)

5
1) LDA, TolS(O)CH2Cl 4) *n-BuLi, CH3CN
CN
THF, –78 °C THF, –78 °C to rt, 91%
O
2) Ac2O, Py, DMAP 5) H3PO4, AcOH-H2O O
94% (2 steps) reflux, 99%
3) n-BuLi, 2-piperidone
THF, 0 °C, 99% * n-BuLi, CH3CN: 5 eq.
T. Satoh et.al., Tetrahedron, 63, 3953 (2007)
 Fukuyama Group - Group Meeting Problems
10/17/2007

1 O
MeO O OTBS
AgOTf·1/2benzene
OTBS C6D6, rt; filt.; MeO
Me O
NTr BnMe3N+CN− N NTr
N Me
MeCN, rt
O
I 33%
E. Vedejs et al., J. Org. Chem., 72, 8506 (2007)
2
O CO2Et Cl NaOEt (10 eq)
+ Me CO2Et
Me N CO2Et N
Cl EtOH, reflux, 2 h H
H
38%

T. P. Curran et al., J. Org. Chem., 61, 9068 (1996)

O
3
Me Me MTAD :
N
N Me
N Me
N Me OH
O N
MTAD, CH2Cl2
H H
N –5 ºC; evapration; 110 ºC N
H H
O C35H37N7O5 O
H O O2, sunlamp 30 min H O
N methylene blue, N
MeOH, –28 ºC, 7.5 h;
Me2S;
N Me Me N Me Me
H H
C32H34N4O2 C32H34N4O3

4 E. J. Corey et al., J. Am. Chem. Soc., 125, 5628 (2003)

1) O
OEt
N
OEt Me Ph
(CO)5W pentane, 93%
Ph Me
2) Ph H N
Ph [(COD)2RhCl]2 (2.5 mol %)
THF-EtOH, 69%
O
R. Aumann et al., Eur. J. Org. Chem., 2545 (1999)
5
Me Me
O N O N O
H2N O
O
Pd(PPh3)4
CHO H H
Na2SO4 PdCl2(CH3CN)2 i-Pr2NEt
O
THF, 50 ºC CHCl3, 60 ºC DMA, 100 ºC N
I H
93% 99% 98%

M. Sasaki et al., Tetrahedron Lett., 48, 4255 (2007)

 Fukuyama Group - Group Meeting Problems
10/24/2007

1 CO2Et
1) 10% NaOCl
CO2Et AcOH-acetone NaHMDS
0 °C, 50% THF, –78 °C; DMP
C20H36O5ClNSi EtO2C
2) TBSONH2 TBAF CH2Cl2, rt
PPTS, MS4A –78 to 0 °C EtO2C O
CH2Cl2, rt, 75% 65%
Cl 99%
S. M. Weinreb et al., J. Am. Chem. Soc., 129, 10342 (2007)

2
1) NaH (1.1 eq), THF-DMF; EtO2C
homoallyl bromide, 72% [Cu(PPh3)Cl]4
N O
EtO2C N Ph
2) hν (300 nm), benzene THF
O 81%* reflux Ph
* 1.7:1 mixture of two diastereomers 89%
(The major diastereomer was used in the next step.)
D. StC. Black et al., Synthesis, 1981 (2006)

3
1) CO2H
PMBO
PPh3, DEAD
THF, rt TFA-CH2Cl2, rt; O
H OH
82% MsCl, TEA, 0 °C; O
C17H21NO5 HO H
EtO2C 2) o-dichlorobenzene H2, Pd/C, MeOH, rt
N
O 150 °C N
74%

Brandi et al., Org. Lett., 2, 2475 (2000)

4
CO2Et
Bn CO2Et CO Me
H 2
Bn HO 1) AcOH
N N
Bn N CO2Me
N 2) MeO2C CO2Me
Bn Me
O H
O toluene, 110 °C
59% (2 steps)

V. M. William et al., J. Org. Chem., 72, 3097 (2007)

5
1) Pd(OAc)2 (1.5 eq)
ethylvinyl ether (4 eq)
NaOAc (2 eq), NaI (0.2 eq)
HO H2C=CHCOC5H11 (20 eq) HO
3) (S)-BINAL-H BrPPh3(CH2)4CO2H
rt, 3 h, 72% (endo:exo = 3:1) 70% KHMDS 4 CO2H

2) PPTS, EtOH 4) 0.25 N HCl THF, 1.5 h C5H11

TBSO 98% (exo only) THF-H2O 54% HO
77% OH

R. C. Larock et al., J. Am. Chem. Soc., 113, 7815 (1991)

 Fukuyama Group - Group Meeting Problems
11/07/2007

1 COCO2CH3
MeLi (2 eq.) PhNHOH
THF, –20 °C; (1 eq.)
1,7-octadiyne
ClCO2Me (2 eq.) benzene N
reflux H CH2CO2CH3
92%
62%

A. Padwa et al., J. Org. Chem., 51, 3125 (1986)

2
CbzHN S CbzHN
Hg(OTFA)2 O
N H2O, CH2Cl2 CO2CH2CCl3
O O N
H
CO2CH2CCl3

T. E. Gunda et al., Org. Lett., 2, 103 (2000)

3
I
1) i-PrMgCl (3.5 eq), THF
O –78 oC to rt; 1) AIBN, allyltributyltin O
Li2CuCl4, allyl bromide benzene, 80 oC HO
HO I
C19H25IO4
2) TMSI, CH2Cl2, 0 oC; 2) 2-methyl-2-butene
O 1N HCl Grubbs' 2nd gen. cat. O O
O
66% (2 steps) CH2Cl2, 40 oC
I 60% (2 steps)

S. J. Danishefsky et al., J. Am. Chem. Soc., 128, 1048 (2005)

4
O
Ph Br
Ph Ph PhCH2NH2 S N Et
O 20 mol% A, DBU p-TsOH, MS4A Ph N Ph
Me
Ph SiMe3 i-PrOH-THF
reflux; 65% Ph HO A

K. A. Scheidt et al., Org. Lett., 6, 2465 (2004)

5
3) DCC, DMSO 5) 5-hexenal
1) hν (quartz) H3PO4, benzene benzene, MS 4A H
OAc pentane, 90% 81% 85%
C8H8N2
2) KOH, MeOH 4) NaCN, NH4Cl 6) 400 °C NC N H
81-94% MeOH, rt 0.01 Torr
88% 49%

R. W. Hoffmann et al., Chem. Ber., 118, 634 (1985)

 Fukuyama Group - Group Meeting Problems
11/17/2007
1
OH 1) cat. MeLi, PhOEt 1) LHMDS, THF, –78 °C;
OMe 210 °C MWI, 80% MeI 92%
(d.r. 3:1) 2) CAN, MeCN/H2O, rt, 96%
tricyclic H
compound O
2) NaOMe, MeOH 3) H2, Pd/C, CHCl3, rt
reflux 4) BF3•OEt2, CH2Cl2, 0 °C
OMe (d.r. 7:1) 95% (2 steps)
HO

T. V. Ovaska et al., Org. Lett., 9, 3837 (2007)

2 OC(O)CO2Me SiMe3 BF3·Et2O 1) Me , BF3·Et2O, –78 °C

OHC –78 °C,4 h; TMS 16 h, 70%
H
C20H24O5
+ 2) Ac2O, Et3N, DMAP, rt , 24 h, 85%
H CO2Et Ba(OH)2·8H2O
0 °C, 2 h
Me OPMB OAc
C10H12O7 C18H28O2Si Grubbs 2nd gen. cat. H
62%
(3x5 mol%), toluene
95 °C, 6 h O H Me
O
chromatographic H
separation Me
of epimers
C24H30O6 OPMB
70%
O. Reiser et al., Angew. Chem. Int. Ed., 46, 6361(2007)
3
Me
N
N Me
O N
(1.1 equiv) O
Me Cl
Ph H (10 mol%) Ph
DBU (15 mol%)
+ β-lactone
intermediate 78%
ClCH2CH2Cl MeO2C Ph
(1.0 equiv) O 0 °C to rt cis:trans = 9:1
> 99% ee (cis)
MeO2C Ph 68% ee (trans)

J. W. Bode et al., J. Am. Chem. Soc., 129, 3520 (2007)

4 n-BuN3, benzene N O
reflux, 24 h; TMS
TMS S N
C14H16OSi
Ph moist silica gel hν, r.t., 8 h
Ph
61% 71%
S. Aoyagi et al., Synlett, 16, 2553 (2007)
5
O O
CAN (2.2 eq.)
O
CH3CN
O O
95%
R. A. Flowers, II et al., J. Org. Chem., 71, 4516 (2006)
 Fukuyama Group - Group Meeting Problems
11/21/2007
1 I2
Me NC (2 eq.)
N
NH N
CH2Cl2
MeO2C I
–78 ºC, 20 h N
MeO2C
Me
85%

R. Lavilla et al., Angew. Chem. Int. Ed., 46, 3043 (2007)

i-Pr i-Pr
2 N N
Cl
i-Pr i-Pr
(20 mol%) O
CHO K2CO3, 18-crown-6
NTs MeO2C O
+
MeO2C toluene
Cl Cl
50 °C, air, 24 h
NHTs
75%
Chen, Y.-C. et al., Org. Lett ., 8, 1521 (2006)
3
O 1) PhCH2MgCl Me
H SnCl4 (2 eq) H
2 THF, rt, 16 h, 60%
Me C16H22O2
O
2) VO(acac)2, TBHP CH2Cl2
Me benzene, reflux, 3 h –78 ºC, 105 min
Me
58%* (dr = 1:1)
80%
* The C2-S isomer was used in the next step.

Marson, C. M. et al., Angew. Chem. Int. Ed., 37, 1122 (1998)

4
Me
N OTf CsF
N Me +
TMS MeCN, 50 °C
Me
N
70% Me Ph

Y. Zhang et al., Org. Lett., 9, 781 (2007)

5
NMe2 NMe2
PtCl2 (cat.)
O S + O S CO2Me
O OMe DCE
50 ºC, 1 h

82%
cis/trans = 69:31

K. Ohe et al., Tetrahedron. Lett., 48, 6651 (2007)

 Fukuyama Group - Group Meeting Problems
11/27/2007
1
1) DEAD, CH2Cl2, 4 °C; H
cyclopentadiene KO2CN=NCO2K
O O Et2NH AcOH, 0 °C
H C15H22O2N2
MeOH 2) KOH, EtOH, reflux CH3CN O H
O 0 °C to rt 3) K3Fe(CN)6, H2O reflux
93% (3 steps) O
90% 80%

R. D. Little. et al., J. Org. Chem., 62, 1610 (1997)

2
O2 N O
N
NO2PF6 Furan (excess)
TMS
CHCl3-MeNO2 CHCl3-MeNO2
0 ºC to rt 50 ºC O
CHO
12-22% 38%
Phillip. E. Eaton et al., Synthesis, 2013 (2002)

3
1) triplet oxygen, hν
Me tetraphenylporphine(TPP) S
CCl4, 0 °C Lawesson's reagent
CO2H IR: 1835 cm-1 O
2) cat. conc. H2SO4 toluene, reflux
35% (2 steps) 40%
3) Ph3P
CHCl3, –30 °C
59%
W. Adam, L. Hasemann, Chem. Ber., 123, 1449 (1990)

4 MesN NMes
Cl
Ru
Cl
O NO2
3) NBS, AIBN O
1) Cat A, CH2Cl2 CCl4, reflux
O rt, 74% 52% K2CO3
H HO
2) CrO3 4) TFA, CH2Cl2 THF
NBoc 3,5-dimethylpyrazole rt rt N
CH2Cl2, –20 °C
77% 87% (2 steps)
T. Honda et al., Org. Lett., 6, 87 (2004)

5 OMe OMe
(CH2OH)2
p-TsOH (cat.)
O Me
Me toluene, reflux O
O 100%
OMOM H

K. Ogasawara et al., Org. Lett., 3, 1737 (2001)

 Fukuyama Group - Group Meeting Problems
12/12/2007
1
OMe O
t-BuLi, HMPA, –78 C to rt; OMe
N hν (>500 nm), –78 °C; NH4Cl
CONHtBu
Ph THF
MeO
Ph
OMe 24%

J. Clayden et al., J. Am. Chem. Soc., 125, 9278 (2003)

2
O O
B B Cl
H O O 1) cat. [Rh(cod)2]BF4 H Ph
Br n-BuLi n-BuLi PhH, reflux, 58%
C24H40B2O4 Ph
Br THF-Et2O THF-Et2O 2) cat. PdCl2(dppf)
H –110 °C to rt –110 °C PhI (2 eq), KOH aq. H
DME, 60 °C, 89%
84% 48%

T. Hiyama et al., Chem. Lett., 35, 1222 (2006)

3 Me
Me
Me
HgCl2 (1 eq) S I
O
NaSO2Ph O (1 eq) mCPBA
DMSO-H2O; NaH (1 eq) BF3·OEt2
C13H14O3S
NaOH, Na2CO3 DMSO-THF CH2Cl2 CH2Cl2
0 °C to rt –78 °C to rt
84% SO2Ph
95%
74% 60%

J. Bäckvall et al., J. Org. Chem., 60, 3586 (1995)

H
4 1) N
O

I O
OSiEt3 cat. piperidine, MeOH O
MAD 60% (2 steps) NH
O Bicyclic
toluene compound
2) TBAF, THF
MeO2C –20 oC 3) CrO3, H2SO4, acetone MeO2C
4) toluene-MeCN, 90 oC I
73% (3 steps)

T. Fukuyama et al., Angew. Chem. Int. Ed., 39, 4073 (2000)

5 1) NaHMDS 3) PhCHO
THF LiHMDS
Cl –78 to –30 °C THF, –78 °C
82% 98% O Ph
Ph
N CN 2) MeOTf 4) 50 °C N Me
Bn CH2Cl2, 0 °C neat, vaccum
83% 4h
81%

O. David et al., Chem. Commun. 2500 (2007)

 Fukuyama Group - Group Meeting Problems
12/18/2007
1) Ph Ph
1
HO OH 1) DDQ
TMSOTf, TMSOMe CH3CN/H2O I O
CHO THF, −78 °C, 83% 60 °C CAN O
bicyclo
compound
2) NIS (2.5 eq), CH3CN; 2) NaClO2, NaH2PO4 CH3CN-H2O O
H2O (5.0 eq) 2-methyl-2-butene rt;
62%* t-BuOH-H2O K2CO3
* other stereoisomer obtained in 18% yield 84% (2 steps)
80%
Y. Kita et al., Angew. Chem. Int. Ed., 44, 734 (2005)

2 O
Li (powder) (* eq) Me
TMSCl (* eq) H O CF3 N O
N C16H32N2Si2
Me TBAF H
N theoretically (2.0 eq) N
45%
58%
Daniel L. Comins et al., Org Lett., 8, 179 (2006)

3
Me Me MeONa (1.1 eq.) PhSNa (1.5 eq.) O
O O dry Et2O MeOH
O HO
O + C9H13O5Cl O
Me OMe reflux, 2h reflux, 0.5h
Cl Cl PhS
CHO
95% (two steps)

S. Tsuboi et al., Heterocycles, 66, 503 (2005)

n-BuLi (3.0 equiv)
4 TMP (3.0 equiv)
O O EtMgBr LiCl (6.0 equiv) O
(1.2 equiv) THF, 0 °C; TFA HO
N N O
THF C10H21 CH2Cl2
I
0 °C to rt C10H21
OPMB
(5.0 equiv) 96%
88%
–78 °C to rt

66%, dr = 90:10
S. P. Marsden et al., Synthesis, 3263 (2005)
S. P. Marsden et al., J. Am. Chem. Soc., 129, 12600 (2007)

5
*vinyllithium n-Bu3SnH TBSO Me
TBSO S
1) toluene, 150 °C THF, –78 °C; AIBN (cat.) Me
O O benzene O
2) Raney Ni *2,3-dibromopropene
THF, 60 °C –78 °C reflux O
80% (2 steps)
79% 81% (3:1)
(* 1 eq.)
J. L. Mascareñas et al., J. Org. Chem., 58, 5585 (1993)
J. L. Mascareñas et al., Org. Lett., 3, 1181 (2001)
 Fukuyama Group - Group Meeting Problems
12/25/2007
N
1) Me
1 S

OTES (1.2 eq)

ZnCl2 (2.0 eq)
CH2Cl2, rt, 14 h TESOTf (1.2 eq) Me
O Et3SiH (20 eq) H H
83%, (dr > 19:1) Me O OH
Me IR = 1827
H 1714 cm-1
2) O3, CH2Cl2 CH2Cl2 (0.01M) O
OBn –78 ºC, 3 min; 0 ºC, 6 h OBn
Ph3P, –78 ºC, 6 h
89% 67%
D. Romo, et al., J. Org. Chem., 72, 9053 (2007)
2
H2N
O Me Me OH
Me Me HN 1) AlMe3, CH2Cl2, 0 °C, 76%
O
2) Na2WO4•2H2O, H2O2-Urea N
O N
O MeOH/H2O, 46%
N 3) silica gel HO HN
H H CHCl3-MeOH-i-Pr2NEt, 63% O

S. Omura et al., Org. Lett., 7, 941 (2005)

3
OMOM
1) Pb(OAc)4 (2.4 eq)
MeOMOM
Me Me
CH3CN, rt, 19 h, 84% HO
HO Me
2) LiAlH4, THF
HO
OH OH

S. Arseniyadis et al., Org. Lett., 9, 4745 (2007)

4 3) LHMDS, HMPA
THF, –78 ºC; O
1) PhSH, Et3N AcOH
O
THF 45% (3 steps)
Br
2) NaIO4 4) toluene, CaCO3
CO2Et reflux
MeOH-H2O
78% CO2Et

M. Pohmakotr et al., Tetrahedron Lett., 41, 377 (2000)

5
OH
O
CHO + N
Me N
C6D6

55% Me

J. Streith et al., Tetrahedron Lett, 27, 3135 (1986)

 Fukuyama Group - Group Meeting Problems
01/22/2008
1
MeO2C CO2Me
H
O O Br2 (2 equiv.) DBU O OH
CHCl3, rt THF, 55 °C Br
Me 80% 70% Me

G. Grohmann, et al., J. Org. Chem., 60, 554 (1995)

2
OMOM 1) Bestmann's rgt Bu3SnH (slow addition) OH
O K2CO3, MeOH AIBN, toluene, reflux; O
98% evaporation;
CHO
H 2) 5% HCl SiO2, CH2Cl2 H
DCE-H2O
H 96% 57% H
NCbz NCbz

H. Muratake, et al., Tetrahedron, 62, 7093 (2006)

3
O
NC
N NH2 N
CN KOH
NH
DMF, rt
O O O
95%
CN

V. J. Ram, et al., Tetrahedron Lett., 48, 7982 (2007)

4 1) CCl3CONCO, CH2Cl2
0 °C; evaporation;
Me
K2CO3, MeOH/H2O Me
96% H
O N O
2) PPh3, CBr4 O
OiPr OMe
Et3N, CH2Cl2 OiPr
OH –20 to 0 °C;
Bu3SnOMe, MeOH
74%

Y. Ichikawa et al., J. Chem. Soc., Perkin Trans. 1, 1449 (1994)

5
Ph
Et
Ph
diketene

Et TMSOTf N O
O
62% O Me
NH
A. Padwa, et al., J. Org. Chem, 60, 2952 (1995)
 Fukuyama Group - Group Meeting Problems
02/06/2008
1 BnO R Me Me
OH Me
H MeLi, THF, h!, PhH;
ClCH2COCl, Et3N –78 °C; evap; R Cl
R=
toluene, reflux Me
Et2O, –78 °C to rt TFAA; BnO Me O O
OEt basic work up
54% 65%
76%
R. L. Danheiser et al., Org. Lett., 21, 3407 (2000)

2 Cl 1) DBU (1 eq.), THF; Cl

Me COCl2 (10 eq.) Me H
Me
Et3N, 0 °C to rt;
H filt; evap H2SiF6 Martin sulfurane (ex.) Me H
TBSO Me
O C20H24ClNO3 O Me
H
O Me 2) SmI2 (8 eq.), LiCl, MeCN CH2Cl2-benzene Me
t-BuOH, –78 °C 60 °C O
O 89% (2 steps) 73% N
N 95%
H H

C26H38ClNO4Si C20H22ClNO2

J. L. Wood et al., J. Am. Chem. Soc., 130, 2087 (2008)

3 1) ClO2S N · O Br
10 °C; 1) TBAF, rt, 57%
NaHCO3, NaHSO3 NaOH aq. 2) CBr4, Ph3P
H2O, –20 °C, 62% Et4NBr rt, 64% H
OAc bicyclic
compound H H
2) (4 eq.) 91% 3) n-Bu3SnH, AIBN N
toluene, reflux O
OTBS
41%
n-BuLi (4 eq.)
CuI (2 eq.) J. D. Kilburn et al., Tetrahedron Lett., 41, 10347 (2000)
THF, –30 °C, 54% S. J. Mickel et al., Org. Synth., 64, 135 (1987)

4 Me BsO
N

CHO
NH2 (1.2 eq) O
DMF-CH2Cl2, rt;

DBU (1 eq);
(CO2H)2, H2O

91%

H. Rapoport et al., J. Am. Chem. Soc., 104, 4446 (1982)

5
O2N H
O O N
H
N 1) Ac2O, THF P(OEt)3

O 2) PhBr, reflux; reflux

N air
H N N
CO2H 35% (2 steps) 54%
H H

C. J. Moody et al., J. Org. Chem., 57, 2105 (1992)

 Fukuyama Group - Group Meeting Problems
02/12/2008
1 N
PhOCOCl
DMAP Tf2O COCl NC
N
N CO2Me
H ClCH2CH2Cl CH2Cl2 toluene
MeO2C reflux 0 °C to reflux; 75 °C NH COCl
TMSCN, rt
66%
68%
P. Magnus et al., Tetrahedron, 58, 3423 (2002)

1) O2, MB*, h"

2 CDCl3, rt
O
30 sec
Me • 2) O2, MB*, h"
n-BuLi MeOH, 8 °C Me O
O AgNO3 on SiO2 C20H30O TMSCl 2 min
Me O
Me ! = 7.21, d, 1H Me
hexane-DCM(5:1) THF 3) SiO2 O
H ! = 6.12, d, 1H
rt, 90% rt, 95% rt, 30 min, 73% H

Me Me * MB = "methylene blue"
Me Me

G. Vassilikogiannakis et al., Org. Lett., 9, 5585 (2007)

3 Me
CO2tBu
I Pd(OAc)2 (15 mol%) Me
PPh3 (33 mol%)

norbornene (7 eq)
TsN CO2tBu Cs2CO3, DME
TsN
I 62%

M. Lautens et al., Angew. Chem. Int. Ed., 46, 1485 (2007)

4
1) SO2Cl2
MT-sulfone CHCl3, reflux
n-C6H13 Me Bu3P=CHCN 99% OH
C17H28O2S2
OH benzene 2) AgNO3 n-C6H13 Me
120 °C MeCN-H2O
81%
72% 3) LAH
THF, 0 °C

T. Tsunoda et al., Tetrahedron Lett., 36, 2531 (1995)

5
Br 5 mol% [RhCl(cod)]2
NaH (2 eq.) 1) CHBr3, NaOH 10 mol% DPPP O
DME, 60 °C; BnEt3NCl CO (1 atm)
C13H16
4'-methylacetophenone CH2Cl2-H2O p-xylene, 130 °C
PPh3 Ar
70 °C reflux, 54% Me Me
Br 2) Zn, AcOH, 56% 82%
83% Ar = 4-MeC6H4

M. Murakami et al., J. Am. Chem. Soc., 129, 12596 (2007)

 Fukuyama Group - Group Meeting Problems
02/27/2008
1 1) DIBAL-H
CH2Cl2, –78 ºC to rt;
Me OTIPS SiO2 HO
2) DIBAL-H NMe
CH2Cl2-THF, –78 ºC; Me
O H
CN NH4Cl aq., rt Mg, MeOH;
Tetracyclic
Compound
3) NaBH3CN, AcOH HCl aq.
CH3CN, rt;
N NaBH3CN, formaldehyde 64% N
Ts 70% (3 steps) H

S. F. Martin et al., J. Am. Chem. Soc., 123, 5918 (2001)

O
2
O
[Rh[CH(CH2)6CO2]]2 (0.5 mol%) O
H
DMAD*
N2 MeO2C
N CH2Cl2, rt MeO2C H
O 70% N
*theoritically 1 eq.

A. Padwa et al., Tetrahedron Lett., 34, 7853 (1993)

3
I i-PrMgCl (1 eq.) TiCl3 (2 eq.)
O THF, 0 ºC; Zn (4 eq.)

N BzCl (1.5 eq.) DME, reflux

Me 0 ºC to rt N
Me
82%
quant.
B. Z. Lu et al., Org. Lett., ASAP (doi: 10.1021/ol7029905)

4
O 1) LHMDS 1) SmI2, HFIP
TMSCl THF-HMPA O
THF, –78 ºC 1 N HCl –78 ºC, 46%
C13H14O2
2) Pd(OAc)2 THF 2) TFA
CH2Cl2, 0 ºC O
MeCN Me
68% (2 steps) 85% 86%
TBSO
HFIP = hexafluoro-2-propanol
C19H30O2Si
K. C. Nicolaou et al., Angew. Chem. Int. Ed., 45, 7086 (2006)
 Fukuyama Group - Group Meeting Problems
03/05/2008
1) NaClO2
1 i-Pr 1) KHMDS NaH2PO4•2H2O
Me
H THF, –30 ºC 2-methyl-2-butene
N 83% t-BuOH-H2O, 0 °C i-Pr
O Bicyclic O
Compound O
Me O Ph 2) TPAP, NMO 2) NaBH4* N
MeCN MeOH H
Br quant. 93% (2 steps) O Ph

*Reduction of N-Cl bond

S. G. Pyne et al., J. Org. Chem., 73, 2943 (2008)

2
O Cl
Me
N
Me H O
H2SiF6
Me Me
TIPSO
H Me MeCN, 65 °C H Me
O
Me Me
O H
N
H
J. L. Wood et al., J. Am. Chem. Soc., 130, 2087 (2008)
3
CO2Et
O DEAD (2.5 eq.) EtO2C N
PPh3 (1.2 eq.) N

toluene Ar
Ar
Ar Ar reflux H N N
EtO2C CO2Et
Ar = 2-(trifluoromethyl)phenyl 74%

V. Nair et al., Angew. Chem. Int. Ed., 46, 2070 (2007)

4
O
SnMe3 PMP
1) Pd(PPh3)4 (14 mol%) 3) SmI2 (2.5 eq) O
LiCl (8.2 eq), CuCl (6.9 eq) HMPA, THF O
Me Me DMSO, 60 °C, 78% rt; PhSeBr, 50% O
O PMP
O Me 2) hv (450W Hg lamp) 4) mCPBA (1.05 eq)
Ph O diisopropylamine –78 °C, 86%
O Me Me Me
Et2O, 82%
OAc Me
Me
E. J. Sorensen et al., J. Am. Chem. Soc., 128, 7025 (2006)
5
t-BuLi, Et2O, –78 to –45 ºC; 1) TBAF, THF, 98% S a= O
a, Et2O, –78 to –25 ºC; 2) MsCl, Et3N,CH2Cl2
S S S TBSO Bu
b, HMPA/Et2O, –78 to 0 ºC 3) K2CO3, MeOH N
TBS 5% Na-Hg, Na2HPO4 Bu Ts
56% Pr N
95% (2 steps) b=
Pr

A. B. Smith, III et al., Org. Lett., 6, 1493 (2004)

 Fukuyama Group - Group Meeting Problems
03/12/2008
1
n-BuLi, THF NBS (1 eq)
Br CHO
–78 °C; THF-H2O;

PhCHO 1N HCl Ph
O –78 °C O
72%
90%

P. J. Walsh et al., J. Am. Chem. Soc., 130, 4097 (2008)

2 OH OH
(COCl)2, DMSO
–78 °C;

Et3N O
N –78 °C to rt; N
Me Me
acidic work up

67%
J. C. Menendez et al., Synlett, 2792 (2007)

3 O OH

1) Li, liq. NH3 Me CO2Me

OMe EtOH, THF hν, AcOEt;

–78 °C Zn, CH2Br2, TiCl4 evaporation; Me Me
Me Me C9H14 O
2) 1N HCl, THF THF-CH2Cl2 aq. Na2CO3
59% (2 steps) MeOH HO Me
62% O
77%

H. Takeshita et al., Bull. Chem. Soc. Jpn., 68, 2393 (1995)

4 1) NaNO2
aq. HCl, 0 °C;
OH

3) H2 (50 psi) O
Me O Me
NH2 cat. Pd/C
90% EtOH, 70%* Me N
NO2 C10H9N3O3 N N
2) conc. HCl 4) NaNO2 N
H2O aq. H2SO4
rt 0 to 60 °C
94% 91%
*The double bond of the enone is not reduced under this condition.
C. Venturello et al., Synthesis 283 (1979)
A. M. Almerico et al., J. Med. Chem. 48, 2859 (2005)
5
O
CO2Me MeO2C
Me 1) PhN2BF4, Py H2, Pd/C
NO2 CO2Me NH CO2Me
H2O, –10 to –5 °C 5% HCl

2) NaBH4, MeOH MeOH

MeO N CO2Me 70% (2 steps) MeO N CO2Me
66%
OMe OMe

S. M. Weinreb et al. J. Org. Chem. 47, 2833 (1982)

 Fukuyama Group - Group Meeting Problems
04/02/2008
1
1) Br2 1) L-selectride
Me AcOH/H2O (1:1) THF, −78 °C; 10% Na(Hg)
Me H
O 0 °C, 77% PhNTf2, 70% Na2HPO4
N tetracyclic H
H compound*
2) toluene (0.05 M) 2) HCO2H, Et3N THF/t-BuOH N
SO2Ph reflux, 70% PdCl2(PPh3)2 (3:1) H
*except for Ph group DMF, 60 °C
84% 82%

K. M. Peese and D. Y. Gin et al., Org. Lett., 7, 3323 (2005)

2
1) PhI(OH)OTs (1.0 eq)
p-TsOH, MeOH
–72 to 30 °C, 2.5 h;
O 1) vinylMgBr refrigerator O
THF, 89% 2 weeks, 55%
O
C15H22OSi
2) HMDS, I2 2) cat. RuCl3, NaIO4 O O
CH2Cl2, 99% H2O-CCl4-MeCN (3:2:2) C24H24O4
1.5 h, rt, 83%
C10H10O

L. F. Silva et al., Org. Lett., 10, 1017 (2008)

3
NaNO2 (xs)
LDA (1.05 equiv) CH2Cl2-Ac2O-AcOH
O Et2O, 0 °C; rt; O
Ph N OtBu Ph N
N OMe
PhMgCl (1.2 equiv) filtration;
Me Me ZnCl2 (1.2 equiv) evaporation; Me Ph
THF, –78 °C to rt NaHCO3, MeOH
reflux
74%, dr = 87:13
84%
P. Somfai et al., Angew. Chem. Int. Ed., 47, 1907 (2008)

4
Me
Me 1) AuCl (1 mol%)
Me Me
CH2Cl2, 88% Me
Me
2) HCl, MeCN
91% O
OTIPS

S. A. Kozmin et al., J. Am. Chem. Soc., 126, 11806 (2004)

 Fukuyama Group - Group Meeting Problems
04/09/2008

1
1) HC(OMe)3
OH MeO OMe
1) ethyl vinyl ketone* mesitylene
OMe DAIB*, MeOH, 98% 220 ºC, 70% O
C17H28O4Si
2) TMSOTf*, Et3N* 2) 1% (CO2H)2 O
benzene, 99% Et2O, 95% Me
Me Me

*theoretically 1 eq. C.-C. Liao et al., J. Org. Chem., 73, 2554 (2008)

2
O MeO
L-Selectride 1) Pd(PPh3)4, LiCl, CO KH, 18-C-6
THF, -78 °C; Bu3SnH, THF, 70 °C THF;

Me PhNTf2, 82% 2) Ph Ph –78 °C to rt Me2SO4 Me

71% 0 °C, 98%
OBn TsN NTs
B OBn

A. B. Smith. Ⅲet al., J. Am Chem. Soc, 129, 14873 (2007)

3
(–)-sparteine (1.2 eq)
s-BuLi (1.2 eq)
Boc Et2O, –78 °C;
N BocHN Me
BEt3 (1.4 eq), –78 °C; OH
TMSOTf (1.0 eq)
–78 °C to rt;
NaOH, H2O2, H2O
0 °C to rt

58%, 90% ee

V. K. Aggarwal et al., Org. Lett., 10, 141 (2008)

4
3) O3
1) TiCl4,CH2Cl2 CH2Cl2, –78 °C; O
Me
–78 to 0 °C, 68% Me2S, 96%
TMSO
Me N
N3 2) PCC, NaOAc 4) t-BuOK
O O
silica, CH2Cl2 t-BuOH, 40 °C
85% 80%

Y.-Q. Tu et al., Org. Lett., 10, 1763 (2008)

 Fukuyama Group - Group Meeting Problems
04/16/2008

1
I O O
O + CO2Et LDA (1 eq) I
Ph OEt
Ph SiMe3 N2 THF 0 °C
–78 °C;
84%

K. A. Scheidt et al. Chem. Commun., 1926 (2008)

2 1) cyclopentadiene, Et3N 3) KH, THF, 0 °C to rt; O

TFE/Et2O (1:1) vinyllithium
O −78 °C to rt −78 °C to rt, 67%
tricyclic
Br Br compound H
2) NaBH4, EtOH 4) DMP, CH2Cl2, 0°C H
64% (2 steps) 76%
5) Grubb's cataylst
ethylene, CH2Cl2
75%
M. Harmata et. al., Org. Lett., 7, 2563 (2005)

3
1) O
MeO OMe

AcOH (COCl)2
reflux, 2 h DMSO cat. TFA
NH2 92% CH2Cl2; 1H-NMR:
PhNH2 N
1H
2) ethyleneglycol Et3N MeCN OH
N Cl δ = 9.75 ppm N N
KOH, DMSO –78 °C reflux, 4 h
50 °C, 94% Ph
84% 90%

X. Bai, Q. Dang et al., J. Org. Chem., 73, 3281 (2008)

4 1) Et3N, DMAP, DCC

Meldrum's acid
NHTs CH2Cl2; concentration; 3) CuOTf, CH2Cl2 O
MeOH, reflux, 72% 50%

N CO2H 2) Et3N, p-ABSA 4) LiCl, H2O N

Boc CH3CN, 86% DMSO, 130 °C Boc N
Ts
87%

Y. Qin et al., Angew. Chem. Int. Ed., 47, 3618 (2008)

 Fukuyama Group - Group Meeting Problems
04/23/2008

1
1) PhC(O)CO2Et 3) t-BuOK
neat, 90 °C toluene, reflux, 60 %
CO2Me
N 2) TsNHNH2, HCl (gas) 4) HCl (gas) N
H DME, reflux MeOH, 0 °C, 100 % H H
Ph
80 % (2 steps) ·HCl
Ritalin

J. D. Winkler et al. J. Org. Chem., 63, 9628 (1998)

2
OH
O
NaOCN SOCl2, Py PhMgBr P(OMe)3 HN
R O
TFA-Et2O toluene THF, –60 °C MeOH, 60 °C
0 °C to rt
OH
R 88% 79% (2 steps)
85%
R=n-C13H27

S. M. Weinreb et al. J. Am. Chem. Soc., 105, 4499 (1983)

3 O
Ph
Ph

O O2N O
OK (1 eq) L-Selectride H2 (160psi)
(1 eq) MAPh (1 eq) Raney Ni N
Cl HO
C28H33NO7
Oi-Pr CH3NO2/CH2Cl2 CH2Cl2 THF MeOH H
–6 °C –78 °C –78 °C O
O 64% HO
69% 94% 91%
C8H11NO4
Ph Ph
O O
MAPh = Al
Me
Ph Ph
(used as Lewis acid)
S. E. Denmark et al., J. Am. Chem. Soc., 118, 8266 (1996)

4
HO 2) p-TsOH 1) Ph3P=CHCO2Me
N
MeOH, rt CH2Cl2, rt MeO2C
CO2Bn 93% 93%
bicyclic HO HN
xylene compound
3) (COCl)2 2) Zn Me
reflux DMSO, CH2Cl2; AcOH-H2O, 50 °C H
84% Et3N, –78 °C 94%
OTHP
97% 3) 1,2-dichlorobenzene
reflux
84%

Z. Zhao et al., Org. Lett., 1, 681 (1999)

 Fukuyama Group - Group Meeting Problems
05/07/2008

1
CHO N
O H
NH•HCl 1) CH2Cl2, rt, 3 d; neutralize Me
+ O
N Me O
H 2) THF, rt, 12 h, 69% N O
MeO2C 3) Et3N, THF, reflux, 32% H
Cl CO2Me

M. E. Kuehne et al., Tetrahedron, 39, 3707 (1983)

2
(COCl)2
Me DMSO, Et3N (PCy3)2Cl2Ru=CHPh O
H Me
OBn OsO4, NMO CH2Cl2, –78 ºC; CH2Cl2, reflux; LHMDS
OBn tBuOMe-tBuOH-H O OBn
MgBr LTA THF
2
Me –100 ºC OBn
HO Me
94% 78% 95%
85%

M. Hirama et al., J. Am. Chem. Soc., 125, 10772 (2003)

1) NBS, Me2S, CH2Cl2

Z
–20 ºC to rt 3) mCPBA, CHCl3 TBSO
TBS OH CN
2) n-BuLi, CH3CN 4) NaHMDS, THF
THF, –80 ºC –30 to 5 ºC

K. Takeda et al., J. Org. Chem., 70, 10515 (2005)

BCl3
medium ring
intermediate quant
solvent
I (CH2Cl2 or toluene?) (determined by GC)

R. Priefer et al., Tetrahedron Lett., 49, 2677 (2008)

 Fukuyama Group - Group Meeting Problems
05/14/2008

1
1) t-BuLi (2.4 eq), Et2O, –10 ºC, 4 h; 1) t-BuOK (1.2 eq), TIPSCl (1.2 eq)
LaCl3·2LiCl (1.3 eq), –70 ºC, 5 min; THF, rt, 1 h;
NHBoc O NBoc LDA (5.0 eq), –50 to –30 ºC
, –70 ºC to rt, 1 h, 75% 2 h, 77% NH2

2) t-BuOK (0.1 eq) 2) TFA–CH2Cl2 (1:10) N

THF, 70 ºC, 4 h, 90% 0 ºC to rt, 2 h, 98% H

K. C. Nicolaou et al., Angew. Chem. Int. Ed., 47, 4217 (2008)

2
OTES 1 mol % OTES OTES
15 mol %
Pd(OAc)2 Pd(OAc)2

K2CO3, n-Bu4NCl dppb

N N N Me
N Me HCO2Na N MeCN, 80 °C N
MeO2C DMF, 80 °C MeO2C MeO2C
I
48%
80%
Me
L. E. Overman et al., J. Am. Chem. Soc., 130, 5368 (2008)

3
Me2N 1) DMAD, MeCN CO2Me
S 25 ºC, 52% CO2Me
N
2) MeCN, reflux
Me 90% Me2N N Me

M. Alajarín et al., J. Org. Chem., 71, 5328 (2006)

NH2
4
N
Me
CO2Me 1H NMR
Br2 Cs2CO3

cyclohexane MeCN δ 2.94 (d, J = 2.8 Hz, 1 H)

NHTeoc 0 °C to rt δ 2.98 (d, J = 2.8 Hz, 1 H)
91%
45%
N CO2Me
PPh3AuCl (1 mol%) H
TBAF AgOTf (1 mol%)

THF CH2Cl2 NH
reflux N H
61% Me
89%
R. L. Funk et al., Org. Lett., 8, 3995 (2006)
 Fukuyama Group - Group Meeting Problems
05/21/2008

malononitrile (3 eq) TMS Me

TMS
Et3N (1 eq)
Me
toluene, reflux, 2 h NC CN
O NH2

S.-X. Liu et al., J. Org. Chem., 73, 3596 (2008)

2 1)
NC (1.2 equiv) O
CHCl3, 150 °C (microwave) Ph
O 75%
CO2H O N
Ph 2) LHMDS (1.2 equiv)
THF, –78 °C to rt;
concentration;
TFA-CH2Cl2, rt
75%

S. J. Danishefsky et al., J. Am. Chem. Soc., 130, 5446 (2008)

3
Me
1) HO
O
O
CH2Cl2 MeO O O
MeO O Me OH

2) 35 °C, 64 h, Et2O; Pr
Cr(CO)5
DDQ, CH3CN
51%
O

M. F. Semmelhack et al., J. Am. Chem. Soc., 104, 5850 (1982)

4
1) n-BuLi, THF, DMPU, –78 °C;
trimethyl 4-bromoorthobutyrate, –78 °C to rt
2) H2, Lindlar cat., py., MeOH HO
PMBO
3) A, toluene, MS 4A, 45 °C; Et3N, 75°C PMBO N
O
53% (3 steps) Ph
4) Zn(BH4)2, Et2O, –10 °C, 84%
NHOH·HCl
A= OH
Ph C. Kouklovsky et al., Org. Biomol. Chem., 6, 1502 (2008)
 Fukuyama Group - Group Meeting Problems
06/14/2008
1
Ph
Me
HgO (yellow)
Ph Na2SO4 cat. 2-anilinonaphthalene* TsOH
N
Ph NH2 ether, rt neat, rt 200 °C, 10 min

81% 55% Ph

*polymerization inhibitor
J. B. Miller, J. Org. Chem., 24, 560 (1959)
R. Huisgen et al., Helv. Chim. Acta, 91, 783 (2008)

2
1) HBTU 3) HBTU, DIPEA
BocHN CO2H HN
DIPEA A, CH2Cl2;
CH2Cl2 TFA
Bn O Me
95% 84% (2 steps) B
H H
CN N N CO2t-Bu
2) TFA 4) Oxone DMF FmocHN N
Br S CH2Cl2 DMF, H2O 40 °C H
O Bn O Me
MeSPh
41% (2 steps) Me
Me
H
BocN N CO2tBu
HOHN
A B ·oxalate O Me
FmocHN CO2H Me
J. W. Bode et al., J. Am. Chem. Soc., 130, 4253 (2008)

3
OH
CO2i-Pr LDA decane CO2i-Pr
Me
n-Pr O THF 180 °C
−78 °C to rt
74% Me
87%

M. Hiersemann, Eur. J. Org. Chem., 2001, 483

4
4) SPh , t-BuOLi, THF
1) PhI(OAc)2 (1.2 eq) −60 °C, 48%
MeOH, 0 °C, 97% O
OMe OMe O
2) NaH, Me3S(O)I
DMSO, 62% O
C7H6O2
3) 10% HCl(aq.) 5) K2CO3, Me2SO4
MeOH, 88% acetone, reflux, 65%
OH 6) Zn, AcOH OMe O
reflux, 66%
C7H8O2 C17H16O4

D. Mal et al., Eur. J. Org. Chem., 2008, 3014

 Fukuyama Group - Group Meeting Problems
06/18/2008
1 NO *
N
CHBr3* NH2
KOH* (powder) O

Br t-BuOK* TEBACl (cat.) MeLi* NaOMe (ex.)

DMSO CH2Cl2 Et2O pentane

0 °C to rt 0 °C 0 °C
66%
80% 84% 36%
*theoretical amount: 1 eq.

A. de Meijere et al., Angew. Chem. Int. Ed., 30, 1518 (1991)

2
TMS SnBu3 OH
HO Pd(PPh3)4 HO
TMS
HO
Br toluene, 85 °C

62% H

C. Bour et al., Tetrahedron, 62, 10567 (2006)

3
1) Mg(ClO4)2
BnOH, 120 °C, 80%
2) NaN3, Tf2O, TBAB
Me Mn(OAc)3·2H2O* 2N NaOH aq.-n-Hex-MeCN O Ph
Cu(OAc)2*, KOAc 0 °C, 92%
bicyclic compound
O except for Ph H H
AcOH, 70 °C 3) Rh2(OAc)4
Ph O
Ph O O CH2Cl2 O
62% 89%

*theoretical amount: 1 eq.

G. Bruton et al., J. Org. Chem., 69, 122 (2004)

4
1)
Br

t-BuLi, CeCl3
O TMS 67% + diastereomer 13%
H
2) MeLi (0.1 eq)
Ph2O, 195 °C, 1 h; H O
acidic workup
85%

T. V. Ovaska et al., Tetrahedron Lett., 39, 5705 (1998)

 Fukuyama Group - Group Meeting Problems
07/01/2008
1
O O
Rh2(esp)2 (2 mol%) S
OSO2NH2 DAIB (1.1 eq.) HN O

OAllyl toluene, rt, 2 h;

NaBH4, MeOH O
85%

B. Blakey et al., J. Am. Chem. Soc., 130, 5020 (2008)

2
1) Br2
MeOH-Et2O, –40 °C; Et3N O O
H H
NH3 CH2Cl2, 0 °C to rt; O
furfuryl alcohol +
2) TfOH (15 mol%) dicyclopentadiene
THF; H H O
Ac2O, NaOAc 58%
H2O
70% (2 steps)
S. Caddick et al., Tetrahedron, 56, 8953 (2000)
M. M. Salunkhe et al., Synthesis, 1883 (2008)

3
1) Pd(OAc)2 (0.1 eq)
Ph3P (0.4 eq)
wet AcOH, CO (1 atm) 3) CHBr3, BnEt3NCl
reflux, 12 h CO2Me
CH2Cl2-aq. NaOH, rt
Me 50% 50% Me

H 2) K2CO3, MeI 4) Et3SiH, NaHCO3

Me Me OAc Br
acetone, rt (CF3)2CHOH, rt, 12 h H
92% 99% Me Me
C15H24O2 C16H25BrO2

M. Koreeda et al., Org. Lett., 4, 537 (2004)

O NH2NH2·H2O, DMSO; Cl
Ph
Ph H Cl3CCO2Et, Et3N CO2Et
CuCl2 (cat.)

58% (Z/E = 5.7/1)

V. G. Nenajdenko et al., Synthesis, 573 (2004)

 Fukuyama Group - Group Meeting Problems
07/09/2008
1
1) N2CHCO2Et, Pd(OAc)2
Et2O, 60% SOCl2
Cl
2) CH3ONa, CH3OH, 92% CHCl3
(single isomer) 74%
3) LAH, Et2O, 96%

A. Menzeket al., Helv. Chim. Acta, 86, 324 (2003)

2
1) MgBr
LDA (3.2 eq) CeCl3
[Fe(DMF)3Cl2][FeCl4] THF, –78 °C O
O NBoc (3.5 eq) 99% N
CO2t-Bu C29H38N2O7
THF, –78 °C to rt 2) TFA, CO2t-Bu
CH2Cl2, 0 °C N
N CO2t-Bu H CO2t-Bu
H 60–63% 3) (CH2O)n, CSA
PhH, 70 °C

L. E. Overman et al., J. Am. Chem. Soc., 130, 7568 (2008)

3 O
Me Me
Me Me
Me N N Me
(2.5 eq, slow addition)
Pd2(dba)3 (5 mol%) Me O Me Me
L* (22 mol%) Me Me O Me
Ph Me N N Me L* = P N
65 °C, 6 h O
Me
Ph Me
80% (90% ee)

Y. Shi et al., J. Am. Chem. Soc., 130, 8590 (2008)

4 1) NH2
3) mCPBA
Ph Me CH2Cl2 HO
PhH, reflux rt, 3-5 sec
quant. 72%
OHC CO2Et H
2) cyclopentadiene 4) H2-Pd(OH)2/C H
TFA, CF3CH2OH 90% EtO2C NH2
0 ºC, 72%

P. D. Bailey et al., Chem. Commun., 2451 (2000)

 Fukuyama Group - Group Meeting Problems
07/16/2008
1
1) n-BuLi (2.2 eq)
THF, –78 to –40 ºC;
methyl triflate (2.0 eq), –40 ºC;
1) CH3CO2CHO EtOH, –40 ºC to rt O
TBDPSO pyridine, rt 56%
Me O
OH 2) CCl4, PPh3 2) 3% HCl/MeOH, rt,
THF, 60 ºC 94%
85% (2 steps)

T. Minehan et al., Org. Lett., 8, 451 (2006)

2 Et3N (3 eq)
PhSCl (2 eq) xs. H2O2
HO OH A
C16H14O4S2
CH2Cl2 AcOH-H2O
–78 °C to rt 90 °C

74% 75%

cat. Mn(phen)2 xs. Zn

NOH A (1.2 eq) AcOOH (1.5 eq) xs. NH4Cl HO OTIPS
TIPSO CHCl3 MeCN-AcOH THF-H2O
N
90 °C (sealed tube) –15 to 0 °C 70 °C

75%, dr = 1:1* 26% 68%

*The undesired isomer resulted in almost no reaction in the next step (i.e. epoxidation).
A. Padwa et al., Org. Lett., 10, 1871 (2008)

3
Ph Cr(CO)5(THF) (5 mol%)
Et3N (3 eq) Ph
O
THF, rt, 24 h OH
97%

S. Uemura et al., J. Am. Chem. Soc., 124, 526 (2002)

4
O
1) 10% [CpRu(CH3CN)3]PF6
MeO 5 15% SnBr4, 1.5 eq. LiBr
acetone*, 60 °C, 70% 1) Zn, AcOH, 89%
6 CO2Me
+ C19H32O3
2) CrCl2, NiCl2, DMF, 71% 2) H2, Pd/C Me
O MeOH, 91% 4
3) PDC, CH2Cl2, 0 °C, 81%
Me
5
* reagent grade
B. M. Trost et al., J. Org. Chem., 66, 7714 (2001)
 Fukuyama Group - Group Meeting Problems
07/23/2008
1

3) CBr4 (1 eq), hν
1) F3CCH2NCO PhCF3, rt
pyridine 4) Ag2CO3 (1.25 eq)
Me OH Me CH2Cl2, rt, 97% CH2Cl2; AcOH Me OH OH

Me Me 2) AcOBr (1 eq) 5) K2CO3 Me Me

Me
CH2Cl2, 0 °C MeOH, rt
dark 69% (4 steps)

P. S. Baran et al., J. Am. Chem. Soc., 130, 7247 (2008)

2
H
O
N2 Ph Rh2(pfb)4 (cat.)
O N
O
benzene xylene
O O reflux N
94% O Ph
68%

A. Padwa et al., J. Org. Chem., 68, 227 (2003)

3 1) Yb(OTf)3 4) SmI2 (3 eq)

Ph (20 mol%) HMPA (3 eq) Ph
I CH2Cl2 tricyclic THF, 40 °C
98% compound 62%
O (excluding
N + 2) Pd(PPh3)4 the two 5) TsOH N
Ph (10 mol%) Ph-groups) (10 mol%)
MeO2C CO2Me CO2Me
MeCN benzene Ph
reflux 80 °C
3) LiCl (10 eq.) 87%
DMSO-H2O
160 °C
73% (2 steps)

M. A. Kerr et al., Org. Lett., 2008, ASAP

4
OH
Na2CO3
EtOH - H2O EtO2C O
Me 80 °C, 2 h ; xylenes
N N
CN NH·HCl Me
EtO2C CO2Et reflux, 20 h
HO
rt, 0.5 h
58%
78%

B.N.Naidu, Synlett, 547 (2008)

 Fukuyama Group - Group Meeting Problems
08/06/2008
1
3) dimethyl fumarate
NO2 1) PhNHNH2 Et3N, CH2Cl2
Et3N, EtOH 80% H
N H N
2) HCl, MeOH 4) HCl, MeOH, reflux CO2Me
NO2 85% (2 steps) 84% NH
Cl
H CO2Me

Rolf Huisgen et al., Eur. J. Org. Chem., 1998, 379

Rolf Huisgen et al., Tetrahedron , 54, 3745 (1998)

LDA (1.2 eq) NaNO2 (1.5 eq)

THF NaBH4 (3.0 eq) HCl
N –78 °C to rt; TFA Cu(acac)2 (0.20 eq) CuCl (cat.)

o-NO2PhCOCl CH2Cl2 EtOH MeOH MeO NBz

I Et3N –78 °C to rt 0 °C to rt
95%
TMS 57% (2 steps) 81%
(1.1 eq)
S. M. Weinreb et al., Org. Lett., 3, 3507 (2001)

1) LDA (2.0 eq)

O THF, – 78 °C to rt
O O 57% N OEt
+ N3
OEt 2) PPh3 O O
THF, rt
60%
P. Langer et al., Chem. Commun., 3044 (2003)

CO2Me 1) Pd(OAc)2 (1 eq), O2 (1 atm)

O O N
AcOH/THF/H2O (1:1:1)
H O H
H N NFmoc
29% (45% brsm) H
N O
2) Et2NH, THF; evap.
N benzene, reflux, 95% N
HMe H
Me 3) mCPBA, CH2Cl2; evap. Me Me
NaOMe, MeOH, reflux, 54%

E. J. Corey et al., J. Am. Chem. Soc., 124, 7904 (2002)

 Fukuyama Group - Group Meeting Problems
09/03/2008
1
Hg(NO3)2 (1.04 eq)
CH2Cl2
CN –30 °C to rt; 1) conc. HCl aq.
NaOH, MeOH, 0 °C; Bicyclic reflux
+ O
(except for indole) HN
N NaBH4 C20H26N2 2) O2,Adams cat.
H NaOH, MeOH EtOAc; H2, 0 °C HN
(7.0 eq) 0 °C to rt 3) NaOH, MeOH
reflux

C. H. Heathcock et al., J. Org. Chem., 58, 564 (1993)

2
NaHMDS (1.3 eq)
THF, –80 ºC;
O
BnO MeO2C
TBS SiMe2Ph ; O
O Pb(OAc)4 TBSO
–80 to –20 ºC; Bicyclic OBn
O compound
NaHMDS, –80 ºC; MeOH-PhH
O
N 95% PhMe2Si CHO
PhO2S Ph
64%
K. Takeda et al., Org. Lett ., 10, 1803 (2008)

OH OH
1) NaIO4 *NaH Me H H
MeCN-H2O, 0 °C *MeI hν Me
TsN
NTs
2) Zn, NH4Cl THF benzene
dioxane, reflux O Me
Me 72% 52%
62% (2 steps)
*theoretically amount: 1 eq.
V. Singh et al., Synlett, 1222 (2008)

4
O
O hν, aq MeOH, 10 °C; MeLi O H
Tricyclic
O
55 °C, 60% C14H16O3 Et2O
Me OAc –78 °C to reflux Me
OH H
C15H16O5 63%

F. G. West et al., Org. Lett., 10, 3733 (2008)

 Fukuyama Group - Group Meeting Problems
09/24/2008
1
CH3COOH
PMBNH2 MeOOC COOMe
1) MeOH, rt, 12h
PhCHO
NC 2) MeOOC COOMe Ph Me
HClaq, toluene N
100 ºC, 63% PMB

R. W. Armstrong et al., J. Am. Chem. Soc., 118, 2574 (1996)

2
AuCl3 (2 mol%) O
AgSbF6 (6 mol%) H

O toluene, 50 °C

Et 87% Et

Y. Yamamoto et al., Org. Lett., 10, 3137 (2008)

H 1) n-BuLi, THF-DMSO 3) NaBH3CN, TFA N

N –20 to –10 ºC, 80% MeOH, rt, 89%
N
Me 2) TsOH, THF-H2O 4) Raney Ni
MeO2C rt, 73% acetone-cyclohexane N O
H
reflux, 92% Me

Y. Langlois, J. Org. Chem., 50, 961 (1985)

1) H2O2, Na2CO3
EtOH, 0 °C, 95% Cl
OBn
H 2) NaOH 1) Al(Oi-Pr)3 EtO2C H
H O EtOH, rt, 60% i-PrOH, reflux
C21H22O4 H
3) LHMDS, BOMCl 2) SOCl2
O THF, –78 to –20 °C CH2Cl2, 60 °C
53% 97% (2 steps)

D. Y. Gin et al., Angew. Chem. Int. Ed., 47, 6821 (2008)

 Fukuyama Group - Group Meeting Problems
10/14/2008
1
O2
S
1) t-BuOK t-BuOK OTBS
O DMSO, 0 °C THF, –105 °C;
Cr(CO)3 NCS (1 eq), rt;
78% TMS

TsO 2) KBH4 hν, Cl(CH2)2Cl; t-BuOK, –105 °C; H H

H MeOH, 0 °C evaporation; –105 °C to rt
TMS
3) TBSCl CO, MeOH 60%
imidazole 70%
DMF, rt
80% (2 steps)

J. H. Rigby et al., J. Am. Chem. Soc., 121, 8237 (1999)

2
HS PPh2
BH3
N3Tf
CuSO4 DCC DABCO O
HO2C
H2N aq. K2CO3 CH2Cl2 THF HN
CH2Cl2 H2O
MeOH 98 % 70 °C

99 % 80%

J. H. van Maarseveen et al., Angew. Chem. Int. Ed., 42, 4373 (2003)

3
O O NHPh
L-Proline (5 mol%) NHPh O
PhNO EuCl3 (30 mol%)
+
DMF EtOH
O O 105 °C O O O O
86%, >99%ee

43%
Y. Hayashi et al., J. Org. Chem., 69, 5966 (2004)
H. Yamamoto et al., Synlett, 705 (2006)

4
1) NaHMDS (4 eq)
1) PPh3, phenol CCl3CO2H THF, –78 °C;
90 °C, 48 h CCl3CO2Na PhCHO, 90%
Br salt A
PhO Ph
(MW < 400) MeCN, 95% 2) t-BuOK
2) EtOAc, reflux
24 h rt, 2 h, 60%

P. L. Fuchs et al., J. Am. Chem. Soc. 126, 14314 (2004)

 Fukuyama Group - Group Meeting Problems
10/22/2008
1
OMe
NC 1) Pd/C
O CO2Me mesitylene
98% O
NBn
Et TMSOTf, EtNO2 N NBn
2) NaOH, EtOH/H2O (1:1) H Et
74% reflux
75%

Brian L. Pagenkopf et al., Org. Lett., 10, 157 (2008)

CO2Me O
OEt nBu
3SnH
OTMS hν 1) 10% HCl aq. AIBN
Tetracyclic
Compound CO2Me
O ZnCl2, Et2O hexane 2) (imid)2CS benzene
CuBr·SMe2 DMAP, THF reflux
HMPA, THF 95% 85% (2 steps)
O
92% HO
83%

M. T. Crimmins et al., Tetrahedron Lett., 37, 8703 (1996)

1) PhI, CO, CO2 O Me

Me Et3N, Pd(PPh3)4 1) o-NO2C6H4SeCN
OBn 100 °C, 79% P(n-Bu)3, THF, 90%
HO
O O
O 2) BBr3, CH2Cl2 2) H2O2, THF, 85% Ph
O O
95%

K. C. Nicolaou et al., J. Am. Chem. Soc., 130, 11114 (2008)

4 Mg (5 equiv), THF
–65 °C → rt → 65 °C;
CuI (1.1 equiv) 1) NaOH
TMEDA (3 equiv) MeOH-H2O, 65 °C H
–65 to –40 °C; 100%
C16H26O2 Me
Cl
CO2Me 2) (COCl)2
(0.95 equiv) toluene, rt H O
–78 °C 3) i-Pr2NEt
toluene, reflux dr = 3:1
76% 57% (2 steps)

W. Oppolzer et al., Tetrahedron Lett., 27, 5471 (1986)

 Fukuyama Group - Group Meeting Problems
10/28/2008
1
1) nBuLi (2.2 eq),THF, -78oC to rt ;
ICH2CH(OCH3)2* 1) LHMDS (3.0 eq), nBu3SnCl N Ts
  
  HMPA, -78oC to rt, 81% THF, 0oC, 66%
OTBS

2) TBAF, THF, 90% 2) PhI+CN -OTf, CH2Cl2, -40 oC ;

3) BocNHTs, PPh3, DEAD, THF, 89% tBuOK, THF, -40 oC OCH3
4) HCl, MeOH, 85% 56%

* theoretical amount: 1 eq.

K. S. Feldman et al., J.Org. Chem., 61, 5440, (1996)

2
S O
hυ Ph2O PhLi, 0 °C, THF; NMe
Et2N S NMe
hexane aq. NaOH O
reflux
reflux 66% Ph
89%
74%*
*mixture of two stereoisomers

R. S. Grainger et al., J. Org. Chem., 73, 8116 (2008)

3
PhCHO, Na2SO4
Ti(Oi-Pr)4 (0.1 equiv.) Al(OTf)3 (0.3 equiv.) O
OH EtMgBr (4 equiv.) CH2Cl2, –10 °C;
CO2Et
THF-Et2O (4:1) TiCl4 (1 equiv.)
O Ph
51% 55%

K. E. O'Neil et al., Org. Lett., 7, 515 (2005)

4
POCl3 O
CHO POCl3
(12.0 eq.) (12.0 eq.)
MeO Cl MeO MeO
Cl
DMF DMF
O O
Cl 120 °C 80 °C
20 min 20 min

78% 69%

M. Shi et al., J. Org. Chem., 73, 8317 (2008)

 Fukuyama Group - Group Meeting Problems
11/05/2008
1
1)
O O
MeO
MeO
benzene, 75 °C
73% MeO
MeO
O 2) AcOH MeO
MeO
THF-H2O, 100 °C
O 70%
O

D. L. Boger et al., J. Am. Chem. Soc., 108, 6713 (1986)

H COMe
CO2Me O O COMe
CH2Cl2 H CO2Me
+ + N
N
rt H H CO Me
CO2Me Cl N 2
89% CO2Me
CO2Me

E. Karimi et al., Tetrahedron. Lett., 49, 6433 (2008)

3
tBuO N CO2tBu
2C N Ar
O PPh3 H2SO4
Ph Ar MeOH Ph N
toluene N
HN reflux reflux H
Ar = 3-O2NC6H4 98% 90%

Y.-G. Wang et al., Org. Lett., 10, 13 (2008)

4 t-Bu
Si (1 eq.)
O t-Bu
1) LAH, THF OH
O Me AgOCOCF3 (1 mol%) reflux, 94% Me
Me Me
tol 2) Ph(CH3)2OOH (3 eq.)
KH, NMP-THF; Me OH
Me 95% CsF (4 eq.)
93%

K. A. Woerpel et al., J. Am. Chem. Soc., 127, 2046 (2005)

 Fukuyama Group - Group Meeting Problems
11/12/2008
1
TMS O
1) BnBr (1.1 eq.), KOH 1) cyclopentadiene
NO2 H2O;1 N HCl H O N
TBAI (cat.), 78% Grubbs 2nd cat.
C8H13NO5
2) PhI(OAc)2 (1.0 eq) 2) O CH2Cl2, 45 °C;
O O O Grubbs 2nd cat. TMS H
CH2Cl2, 0 ° to rt
N
74% O
O 80%
NaHCO3, THF
61% (2 steps)
C. Kouklovsky et al., Org. Lett., 9, 1485 (2007)

MeO OTES PhCH2N3

O
BF3•OEt2 Rh2(OAc)4

CH2Cl2 CH2Cl2 N
–78 °C to rt, 20 h 0 °C to rt, 20 h Ph

47% 90%

J. Aube et al., Org. Lett., 2, 1657 (2000)

3 TMSCN
H

ZnCl2 toluene, reflux

MsO PhMgBr N
Pd(PPh3)4 (cat.) 50% H CN
Me Me

N3 THF O

85% O2 HN

toluene, reflux
O
62%

K. Feldman et al., J. Org. Chem., 73, 5090 (2008)

O O O
NH4OAc aq. NaOH
PhHN NMe2 PhN
AcOH, 90 °C EtOH
O
82% 91%

D. Dong et al., J. Org. Chem., 73, 8089 (2008)

 Fukuyama Group - Group Meeting Problems
11/25/2008
1
pyrrolidine
OTIPS Pd2(dba)3, t-BuONa hν OTIPS
rac-BINAP [W(CO)6] (10 mol%)
N
toluene, reflux toluene, rt
Br
42% 65%

N. Iwasawa et al., Angew. Chem. Int. Ed., 47, 4906 (2008)

PhCMe2O2H
2 1) NCS (1.0 eq.) Ti(Oi-Pr)4
benzene (–)-DET
A
S S
2) P(OEt)3, 60 °C CH2Cl2
78% (2 steps) (S,S)-C8H17O5PS2
43%, 99%ee
1) A, LiOH·H2O (0.99 eq.) Pd/C CO2H
OMe O THF, 80 °C, 80% H2 (100 psi)
NHBn
MeO H AcOH
2) PdCl2(CH3CN)2 (1 mol%)
acetone, 60 °C;
BnNHOH·HCl 65%
NaHCO3, 60 °C, 70%
V. K. Aggarwal et al., Org. Lett., 6, 1227 (2002)

3
S

N NH2
Cl
H
(10 mol%) O
O ∗ NO2 DMAP (10mol%) D N ∗
O
+ Ph
S
Ph D CHCl3, rt
Ph Ph
(*; 13C)
83% (dr = 97:3) O

W.-J. Xiao et al., J. Am. Chem. Soc., 130, 6946 (2008)

4
Br
1) methylene bromide Br MgBr
LiTMP, THF
–90 ºC (2.2 eq)
PhCO2Et
2) MeONH2•HCl THF
MeOH –42 ºC to rt N N

80% Ph Ph

K. Oshima et al., J. Am. Chem. Soc., 124, 9032 (2002)

 Fukuyama Group - Group Meeting Problems
11/29/2008
1
O O
Li O H H
i-PrO O
, THF, -78 ºC;
i-PrO
CH2=CHLi, 0 ºC; OH
i-PrO O sat NH4Cl aq i-PrO O
OH

Paquette, L. A.; et al., J. Am. Chem. Soc., 124, 9199 (2002)

2
HO H
1) hv, I2
MOMO 1) NaBH4, CeCl3 PhI(OAc)2 MOMO
O MeOH, 89% O
O CH2Cl2, 80%
C29H42O8* H
2) ethyl vinyl ether 2) n-BuLi, THF BnO
BnO CHO NBS, Et2O, 61% −78 °C O
HO 3) Bu3SnH, AIBN quant
benzene, 77% EtO
* 1: 1.2 diaetereomer mixture

H. Nagaoka et al., Org. Lett., 2, 3751 (2000)

3
NHBn
PMBNH2 PMB H
furfural Tricyclic 1) allyl alcohol N O
CO2H BnNC Compound NaH, DMF, –40 ºC, 73% O OAc
I H O
MeOH, 50 ºC (except for 2) Hoveyda-Grubbs' 2nd cat. H
aromatic ring) vinyl acetate H
O
68% benzene, rt, 100%

M. Sasaki et al., Eur. J. Org. Chem., 5215 (2008)

4 1) 1,2-dibromoethane (1.51 equiv)

NaH (3.01 equiv)
DMF, 0 °C;
MeOH, –78 to 0 °C
86% A
δ 1.47 (dd, 2H, J = 7.9, 4.1 Hz)
TBSO N O 2) NaH (1.50 equiv) δ 1.73 (dd, 2H, J = 7.9, 4.1 Hz)
Bn
BnBr (1.50 equiv)
–45 to 0 °C
87%

1) Et3N (10.1 equiv)

TMSOTf (7.18 equiv) N OTBDPS
BocN OTBDPS CH2Cl2, –78 to –20 °C

2) A (1.01 equiv) H
MgI2 (1.01 equiv) BnO N O
Bn
THF, 80 °C (sealed tube)
E. M. Carreira et al., Chem. Eur. J., 12, 8208 (2006)
 Fukuyama Group - Group Meeting Problems
12/3/2008
1 O OAc

Me i-Pr
m-CPBA O
NaOH t-BuOLi (2.2 eq) O S
S PF6- Ph
H2O THF, rt Me
Ph
40 °C 74%
67% i-Pr

T. Fujimoto et al., Eur. J. Org. Chem. 2265 (2001)

2
CO2Et CO2Et
1) HCO2Me 3) n-BuLi, MeOCH2SPh
H Me NaH, DME, 97% THF, -78 °C H Me
O O
2) n-PrSH, TsOH 4) HgCl2, HCl/MeCN
benzene, 50 °C 80 °C, 86% (2 steps)
93%
CHO
S. J. Danishefsky et al., J. Am. Chem. Soc., 127, 13514 (2005)

3 3) TBSOC(O)CF3(1.5 eq.)
2,6-lutidine (0.5 eq.)
0 to 20 °C, 48h, 96%
4) Ti(Oi-Pr)4 (0.5 eq.)
1) Br3CCHO (1.2 eq.) 1.5 M EtMgBr (4.0 eq.)
H2SO4-AcOH (1:1) THF-Et2O (1:1) O
HO 0 °C, 4h, 88%
CO2H 0 °C, 2h, 87%
HO2C C5H8O3
2) BH3•SMe2 (0.5 eq.) 5) NaH (1.0 eq.) OBn
THF, −10 °C, 1h; BnBr (1.0 eq.)
MeOH, 20 °C TBAI (3.0 eq.)
overnight, 83% 0 to 50 °C, 88%
6) SiO2
MeOH-CH2Cl2
97%, 80% ee

P. P. Piras et al., Synlett, 18, 2823 (2008)

4
O
1) cyclopentadiene 1) Me3SiCl, HMDS
CO2H MeOH, 0 °C, 70% pyridine, 0 °C, 92% H
O OH
2) NaBH4, NaHCO3, H2O; 2) BF3·OEt2, 84% H
H2SO4, 75 °C, 43% H O
O

M. E. Maier et al., J. Org. Chem. 67, 8692 (2002)

 Fukuyama Group - Group Meeting Problems
12/16/2008
1

O I
1) ClCO2i Bu, TEA, diethyl ether, 0 °C;
COOH CH2N2, diethyl ether, 0 °C to rt
O
NC 2) 3 mol% [Rh2(OAc)4], CH2Cl2
I CN O

E. Lee et al., Angew. Chem. Int. Ed., 47, 4009 (2008)

H 1) H2O2, NaOH 1) TiCl4, CH2Cl2 H OMe

AcO O MeOH, 85% –78%, 50% HO

2) NaBH4, MeOH 2) HCl, MeOH O

OTBS
Me THF, 91% 80% Me OH
Me 3) TESCl, imidazole Me
DMF, 93%

S. Danishefsky et al., J. Am. Chem. Soc., 130, 13765 (2008)

3
1) O
O
N
O
Ph O
P
Ph
O O
THF-H2O, rt
N3 N2
2) NaHCO3 aq., rt
67%
R. T. Raines et al., Angew. Chem. Int. Ed., Early View (10.1002/anie.200804689)

O2 N CH(NMe2)3 (2 eq) HN

O THF, reflux O
N N
H Me 80% H Me

J. Bonjoch et al., Tetrahedron, 50, 9769 (1994)

 Fukuyama Group - Group Meeting Problems
01/07/2009
1

1) LTA (1 eq) OMe CO Me

3-butyn-1-ol (4 eq) O 2
H CH2Cl2, 37%
N C9H14O3
N CO2Me
2) toluene, reflux IR: 3610 cm-1 (br) 74%
O

J. Warkentin et al., J. Org. Chem., 59, 5071 (1994)

CHO H
BnNHOH AuCl3 (2 mol%)
BnN
CO2Et CH2Cl2 CH3NO2 CO2Et
70 ºC, 1 h
CO2Et O CO2Et
92%
82%

Yeom, H. S. et al. Angew. Chem. Int. Ed., 47, 7040 (2008)

O PhCO2H
MeO BzO H
hν MgSO4
N O
MeCN toluene N
O
O 76% 69%

Booker-Milburn, K. et al. Org. Lett. 9, 4681 (2007)

4
1) NaH, THF, 0 °C;
Me Me Ac2O, 80 °C; BnO CO2Me , 87% O
S C9H12O2S2 BnO
O p-TolSO2Na, NaOAc 2) Br , K2CO3
AcOH, 100 °C DMF, rt, 95% OMe SMe
3) DABCO
71% MeOH, rt, 83%

K. Ogura et al., Bull. Chem. Soc. Jpn., 56, 3543 (1983)

K. Ogura et al., Tetrahedron Lett., 28, 5703 (1987)
 Fukuyama Group - Group Meeting Problems
02/04/2009
1

cinnamaldehyde ZnEt2, ICH2Cl

OH Ph O
H Na2SO4 Et2O, 0 °C;
N
Ph
CH2Cl2 n-BuLi, THF Ph
N
–30 °C
95%, >98%de
72%, >98%dr
V. K. Aggarwal et al., Org. Lett., 5, 1757 (2003)

2 Me
Me OTIPS H H
ZnCl2, CH2Cl2; DIBAL Me O OH
S Et3SiH, CH2Cl2
N –78 to 0 ºC OBn
O H
O
54% (2 steps)
Me OBn
0 ºC
D. Romo et al., Angew. Chem. Int. Ed., 47, 5026 (2008)

3 O
N3
O 1) HMDS 3) CSA N3
O
Cl3C HFIP*, rt benzene, 60 °C H
O 85% 29% N
O OMe
O
2) Ac2O, py. 4) 1N NaOH
NC
CH2Cl2, rt MeOH, rt AcO
OMe 92% 62%
OMe HFIP = 1,1,1,3,3,3,-hexafluoroisopropanol

Y. Kobayashi et al., Angew. Chem. Int. Ed., ASAP

4
O 1) semicarbazide hydrochloride
NaOAc, EtOH-H2O, rt
O 2) LTA, CH2Cl2, –10 ºC; O
2.4 N HCl aq, 0 ºC
3) CH3CN, reflux
44% (3 steps)
J. Warkentin et al., Can. J. Chem., 56, 308 (1978)
 Fukuyama Group - Group Meeting Problems
02/10/2009
1
Cl Pd(OCOCF3)2 (5 mol%)
OH N PCy3 (20 mol%)
Cs2CO3 (1.2 eq)
N i-Pr N N
i-Pr
xylene, reflux, 19 h
(1.2 eq)
77%

K. Oshima et al., Angew. Chem. Int. Ed., 46, 2643 (2007)

2 i-Pr i-Pr
N N
Cl
i-Pr i-Pr O
(20 mol%)
CHO NO DBU(20 mol%) O2 N
+ O
THF, –5 ºC HN
O2N Me
81%
Me

G. Zhong et al., J. Org. Chem., ASAP

3
1) benzaldehyde
NaOEt, EtOH N
N reflux, 88%

CN 2) 1-butanol
reflux, 86% NC
Ph
a 1:1 diastereomeric mixture

D. N. Reinhoudt et al., J. Org. Chem., 49, 269 (1984)

4
O Me
1) COCl2, Et3N 3) H2, Pd/C
Ph O
O MeCN-toluene, 40% EtOAc, 97%
Ph
HN O Ph Ph
2) benzene, reflux 4) Cr(OAc)2, H3PO2
quant. DMF, 94% Me
Ph

J. Fischer et al., Tetrahedron, 42, 2063 (1986)

 Fukuyama Group - Group Meeting Problems
03/18/2009
1
Tf2O (2.0 eq) Me
O Py (5.0 eq)
N CH2Cl2 N
toluene O
OH -78 ºC to rt 130 ºC O S
Me CF3
75% 96%

A. Padwa et al., Org. Lett., 5, 189 (2003)

2
• OMe OH
O Pd/C, H2
nBuLi
SnCl4 (Boc)2O O
O

MeCN MeOH, rt H OMe

N+ THF, –78 ºC;
O Bn H2O –30 ºC to rt NHBoc
82%, dr = 7:1 O
68%
81%
H.-U.Reißig et al., Eur. J. Org. Chem., 1003 (2005)
H.-U.Reißig et al., Eur. J. Org. Chem., 282 (2009)

3 CuI (0.21 equiv)

1) PMBNH2 (2.0 equiv) 1H BnMgBr (3.0 equiv)
NMR (CDCl3):
K2CO3 (1.0 equiv) THF, –30 C to rt; O PMB
THF, rt 7.27 (2H, d) BnBr (1.5 equiv) N
99% 6.89 (2H, d) 0 to 40 °C; Ph
2,3-dibromopropene 4.75-4.67 (2H, m) BnO
2) Na (2.8 equiv) 3.81 (3H, s) AcOH (2.0 equiv)
liq. NH3-Et2O, –33 °C 3.63 (2H, s) 0 °C to rt;
88% Et3N (4.4 equiv) Ph
2.11 (2H, s)
BnOCH2COCl
(1.3 equiv)
–78 °C to rt

50%
M. Shipman et al., J. Org. Chem., 73, 9762 (2008)

4
O Me
Me 1) 1,3-dimethylcyclopentadiene
Eu(FOD)3 (10mol%) 3) LiDBB, THF
toluene, 80 °C, 84% −78 to 10 °C, 57% Me
Me C15H22O H
2) hν, Corex, 79% 4) PDC, DMF Me
O 84% Me

V. H. Rawal et al., Org. Lett., 2, 2711 (2000)

 Fukuyama Group - Group Meeting Problems
04/08/2009
1
O H NBS (1.1 eq)
N CH2Cl2, 0 °C ;
H H2N

EtOH DBU, 0 °C to rt
rt
78% (E:Z = 20:1)
94%

R. J. Thomson et al., Org. Lett., 11, 465 (2009)

2 EtO O
MeLi, THF, –78 °C;
A
TFAA;
EtO O aqueous workup

O
1) n-BuLi, THF, –78 to 0 °C; 3) n-BuLi, THF, –78 °C;
Me
TsCl, 0 °C to rt, 95% A, –78 to 0 °C, 62%
N
OH 2) 2-methylimidazole 4) !, MeCN, 35min; EtO Me
MeCN, 70 °C, 92%
Pd/C, 80 °C, 4h, 26% O N

H. W. Moore et al., J. Org. Chem., 53, 2477 (1988)

S. F. Martin et al., Angew. Chem. Int. Ed., 48, 2569 (2009)

3
MeO2C CO2Me
N N
OMe CO2Me
O O OMe BF3·OEt2 MeO2C
Ar
Ar Ar toluene CH2Cl2
O O
reflux 0 °C H Ar
Ar = 2-Cl-C6H4 91% 65%

V. Nair et al., Org. Lett., 4, 2821 (2002)

4
OH
TiCl4
O
CH2Cl2 N
N3 OTMS
–78 °C to rt
O
78%

T. Q. Tu et al., Org. Lett., 8, 5271 (2006)

 Fukuyama Group - Group Meeting Problems
04/15/2009
1
TrO
n-Bu3SnH TrO
O O AIBN
O
O N benzene
reflux OH
O
64%
G. M. Sammins et al., Org. Lett., ASAP
DOI: 10.1021/ol900481e

2
1) Br(CH2)3PPh3Br
Ph Ph
NaH (2.0 eq.)
O Br
DME, 70 °C, 82% AgOAc (1.5 eq.)
C17H14Br2 + Br
Ph Ph
2) CHBr3, NaOH BF3•Et2O Me
BnEt3NCl TFA, -10 °C
CH2Cl2-H2O 53% 36%
reflux, 54%

M. Murakami et al., J. Am. Chem. Soc., 129, 12596 (2007)

M. Shi et al., Tetrahedron Lett., 50, 1636 (2009)

N
C6H5COCl, KCN 1) CH2=CH2CN, HCl, dioxane, 0 °C to rt
N H2O, rt 2) NaOH aq., rt, 34% ( 2steps ) NC NH

77% C6H5

W. E. McEwen et al., J. Org. Chem., 31, 4110 (1966)

4
1) Tf2O, NEt3
NaH, THF, 0 °C; CH2Cl2, –78 °C
O O n-BuLi; 96% OH
cyclic
compound
OMe benzaldehyde; 2) MeMgBr (2 eq) Ph
2M NaOH toluene
–78 °C to rt
58% 95%
G. B. Dudley et al., J. Am. Chem. Soc., 130, 5050 (2008)
 Fukuyama Group - Group Meeting Problems
05/09/2009
1
Me OAc
Me OAc 1) (COCl)2
CH2Cl2, rt PhSeCl H H
Cu(hfacac)2
C13H18O4 O SePh
O 2) CH2N2, Et2O CH2Cl2 CH2Cl2
CH2Cl2, 0 °C reflux 0 °C
CO2H 67% (2 steps)
50% 78% O Cl

J. S. Clark et al., Chem. Comm., 1079 (2000)

2
activated Zn BnO2C OTBS
O Et2O, reflux; DBU Me
O
Br
BnO A, –30 ºC; benzene, 80 ºC O
B, –30 º C to rt Ph
Me
60%
44%
O
O
TBS
BnO
Ph Br
O B J. S. Johnson et al., Angew. Chem. Int. Ed, 48, 3689 (2009)
A

3
O
1) DAIB, allyl alcohol 3) KH, 18-C-6 O
OMe CH2Cl2, rt, 77% THF, reflux, 97%

OH 2) 4) H2, Pd/C
O O
MeOH, rt, 95%
CeCl2
O
THF, –78 °C, 76%
O OMe

C.-C. Liao et al., Org. Lett., 5, 4741 (2003)

4
3) diallylamine
O 1) TosMIC, KOt-Bu PPh3, Pd(OTf)2
H MeOH, DMF, 68% benzene, reflux CHO
H
SES N
2) DIBAL, toluene 4) 5% HCl SES N
H −78 °C to rt, 90% 68% (2 steps) H

S. M. Weinreb et al., J. Org. Chem., 62, 1920 (1997)

 Fukuyama Group - Group Meeting Problems
05/16/2009
1
O OMe
1) 14M KOH vinyl lithium
MeOH, reflux THF, –78 °C;
bicyclic compound
SPh (except for Ph group) O
2) (COCl)2 MeI, rt
benzene, rt;
Et3N 87% SPh
benzene, reflux
57% (2 steps)
L. A. Paquette et al., J. Am. Chem. Soc., 119, 2767 (1997)

aq. HCHO
NaOAc
HO 80 °C (MW)
NH·HCl
t-Bu N
EtOH t-Bu O
73%

A. Meijere et al., Eur. J. Org. Chem., 1251 (2006)

3 allyl chloride, dIpc2BOMe 1) Pd(OAc)2 (5 mol%)

P(Oi-Pr)3 (35 mol%)
LiN(c-Hex)2, Et2O-THF, –95 °C;
n-BuLi (10 mol%)
BF3·OEt2, –95 °C; CO2 (40 psi)
A, –95 °C; THF, 78% O
O O
CHO O
evap., rt; 2) 50% NaOH
1,4-dioxane-H2O
A NaOH, H2O2, THF-H2O
3) 2 N HCl aq.
0 °C to rt 99% (2 steps)

)2BOMe 64%
dIpc
2BOMe = A. C. Oehischlager et al., J. Org. Chem., 64, 2524 (1999)

1) Tf2O, CH2Cl2
BrMg –50 ˚C, 11 h, 65% CH2OH

O Br
CeCl3, THF 2) LAH, 98%
OMe
76%
M. Harmata et al., Tetrahedron Lett., 43, 2347, (2002)
 Fukuyama Group - Group Meeting Problems
06/03/2009
1
O
MEMO
PhCOCl BF3·OEt2
SnBu3 dihydrofuran Ph
toluene CH2Cl2
SO2Ph reflux O
–78 ºC to rt
83% 45%
M. Pohmakotr et al., Tetrahedron Lett., 37, 4585 (1996)

2 H
O O N
H
S N EDCI O
O Et3N NaOMe HN
O NH
CH2Cl2 MeOH
OEt N 0 °C to reflux; 0 °C to rt
N
Ts 71% Ts
J. J. Tepe et al., J. Org. Chem., 74, 3406 (2009)

3 Ph
Me O
O Ph
N Me
+ CO2Me
N O Me CCl4
80 °C O
CO2Me Me
46 %

J. Hegmann et al., Angew. Chem. Int. Ed. Engl. 27, 931 (1988)

4
CCl3
1) Na2CO3 O
O NH o-xylene 3) P(OMe)3, MeOH
140 ºC reflux HN CCl3
PhS H
2) mCPBA 4) (PCy3)2Cl2Ru=CHPh HO N O
O NH
CH2Cl2 CH2Cl2, rt
–20 ºC, 97% Cl3C
CCl3
(dr=1:1)
N. Chida et al., Org. Lett., 11, 2687 (2009)
 Fukuyama Group - Group Meeting Problems
06/09/2009
1
O
MeMgBr (2.1 eq), THF, 0 °C;
MeO Br PdCl2(PPh3)2 (5 mol%), 65 °C;
+
O MeO
OH DMSO
100 °C
O
Br 61%
B. L. Flynn et al., Org. Lett., 6, 457 (2004)

2
Ph
Me
Ph O N
+ N Ar Ph
Ar benzene/MeCN, 80 °C
Ph Ph
60% Ph Me
Ar = 4-Cl-C6H4
A. P. Molchanov et al., J. Org. Chem., 73, 2396 (2008)

3
O HO H
hν N
H2N Pyrex NiCl2·6H2O, NaBH4

S CH3CN MeOH/THF
0 °C 0 °C to rt
O
100% 56%

J. D. Winkler et al., J. Am. Chem. Soc., 128, 9040 (2006)

4
O
5% aq. H2SO4, rt; 1) Boc2O, 1) DMAD,MeOH OH OH
neutralize; i-PrOAc, rt –10 °C to rt HN
C12H25N3O4 OMe
O MeNH2•HCl 2) 50% aq. NH2OH 2) o-xylene, 120°C N
NaCN, 0 °C to rt MeOH, rt to 60 °C 45% (2 steps) N O
75% (3 steps) Boc Me

Y. L. Zhong et al., Org. Process Res. Dev., 12, 1245 (2008)

 Fukuyama Group - Group Meeting Problems
06/20/2009
1

OTs TsO
NaNO2 N NH
MeOH-H2O, rt; O
O O
Meldrum′s acid
TsCl, pH 7 buffer, 0 °C to rt toluene, 60 °C O
O O O
O
57% 38%

R. L. Danheiser et al., J. Org. Chem., 63, 7840 (1998)

2
Me3S(O)I* OMe
OMe H
NaH*
CO2Et
CO2Et
DMF
rt MeO O
MeO O O H OH
79%

*theoritically 2 eq.
S. Ohta et al., Org. Lett., 3, 1359 (2001)

3
SNH2

O2N NO2 Ph
Ph
Ph Ph PhI(OAc)2
S
N
CH2Cl2, rt
O2 N NO2
98%
M. Shi et al., Tetrahedron, 63, 11016 (2007)

4 OMe
OMe
MeO MeO
SO2Ph
(CH2OH)2 PhSO2Cl NMe
p-TsOH LiAlH4 TEA
O
CO2Me THF THF CH2Cl2 H
NH reflux reflux 0 °C to rt O
OMOM
77% 95% O
82%

K. Ogasawara et al., Org. Lett., 4, 4515 (2002)

 Fukuyama Group - Group Meeting Problems
06/27/2009
1
(CH2=O)n (5 eq.) CO2Me
CO2Me (4 eq.)
toluene, 100 °C, 4 h;
CO2H N
N
H Bu2SnCl2 (0.1 eq.)

78% MeO2C

H. Ardrill et al., Tetrahedron., 50, 5067 (1994)

2
OMe OBn
1) LAH, toluene 3) p-TsOH
O O 80 ºC, 97% benzene, reflux HO
O NH BnO
Ar 2) 3 N HCl aq 4) NaBH4 N
THF, rt MeOH-THF
OBn OBn 90% –78 ºC
63% (2 steps) dr= 2:1 Ar

Ar = OMe
K. M. Brummond et al., J. Org. Chem., 70, 907 (2005)

3 O
H OMe
Ph
O
OMe
O 260 psi H2
O2 N H N
O O Ra-Ni HO
Ti(O-i-Pr)2Cl2 benzene Ph
O Ph 25 ˚C MeOH MeO2C H O
CH2Cl2
–90 to –78 ˚C 68% O
88%
97.7% ee
71%
S. E. Denmark et al., J. Org. Chem., 59, 5672 (1994)

4
O LHMDS (2.2 eq.) 1) Cu(OTf)2 (0.1 eq.) OH O
THF, –60 ºC; CH2Cl2, 98%
t-BuO NH O
Ph OH
I2 (1.2 eq.), –60 ºC 2) LiOH (2.0 eq.)
Ph OMe H2O, 90% NH2
85%
threo
phenylserine

A. Vecchione et al., Org. Lett., 1, 2153 (1999)

 Fukuyama Group - Group Meeting Problems
07/01/2009
1 3) PhSeCH2CH(OEt)2
1) (+)-(Ipc)2BCl, Et3N PPTS, DME, 85 °C, 67%
Et2O, 0 °C; A, –78 °C; H2O2 4) NaIO4 O
OBn
pH 7 buffer, MeOH, rt EtOAc-MeOH-H2O, rt
O OBn
O
OTBS
2) Me4NHB(OAc)3 5) DBU, m-xylene
MeCN, AcOH, –35 °C OMe 180 °C
51% (2 steps) 55% (2 steps)

CHO
A A. B. Holmes et al., Synlett, 972 (1999)

Me
O
2 Cl n-BuLi
B
Cl THF
Cl –78 to –40 °C
A
Cl
H 1) Br2, CHCl3, rt
N NaH, DMF, rt;
Me
N
B, 80-90 °C 2) aq. NaOH
N Cl N
41% from A 89% N

P. J. Crowley et al., Tetrahedron, 62, 8966 (2006)

3 1) Pd(OAc)2 (3.0 mol%) 1H NMR (500 MHz, CDCl3):

n-Bu4NCl (2.0 equiv) d = 9.62 (d, J = 2.3 Hz, 1 H)
4-penten-1-ol
(1.1 equiv) 6.89 (s, 1 H) 3) NIS (3.1 equiv)
LiCl (1.0 equiv) 6.60 (s, 1 H) K2CO3 (3.1 equiv)
3.81 (s, 3 H) MeOH (10.4 equiv) MeO
LiOAc (3.0 equiv)
MeO I DMF, rt, 63% 3.49 (dt, MeCN, rt, 84%
J = 3.6, 2.3 Hz, 1 H) Me
Me 2) A (20 mol%) 2.75 (t, J = 6.3 Hz, 2 H) 4) MeMgBr
CAN (2.0 equiv) (2.0 equiv) HO
2.18 (s, 3 H) THF-Et2O
H2O (2.0 equiv)
O A DME 2.17-2.13 (m, 1 H) 0 °C to rt, 65%
NMe –78 to –30 °C 1.94-1.88 (m, 1 H)
Bn t-Bu 56%, 90% ee 1.81-1.76 (m, 2 H)
N
H
K. C. Nicolaou et al., J. Am. Chem. Soc, 131, 2086 (2009)

4
BuLi, THF, 0 °C, 30 min;
OMe THF, 90 °C, 3 h;
OTMS air, sunlight, hexane, 2 h; HO O
(OC)5Cr Ph , 78 °C to rt; filtration;

Li conc. HCl, acetone, rt, 15 min

Et , –78 °C to rt; H
aq. H3PO4 (quench); Ph Et
filtration; 76%, >98%ee

J. Barluenga et al., J. Am. Chem. Soc., 124, 9056 (2002)

 Fukuyama Group - Group Meeting Problems
07/07/2009
1

O
asymmetric
O bicyclic compound
160 °C 200 °C
O
11%

M. Oda et al., J. Chem. Soc., Chem. Commun., 446 (1976)

2
H
O MgBr

TMSCl, HMPA, CuI Et2Zn, CH2I2 Fe(NO3)3

H
H H
THF, –78 °C hexane, 0 °C DMA O
Ph Ph
50% 56%

K. I. Booker-Milburn et al., Org. Lett., 5, 1107 (2003)

3
1) Zu-Cu
CCl3COCl in DME 3) CeCl3, NaBH4 Ph
Et2O, rt cyclic MeOH, rt Ph
Ph compound
2) Zn 4) ClCO2Me, Et3N
(excluding Ph group)
TMEDA-AcOH DMAP, DCM, rt MeO2CO H
EtOH 52% (2 steps)
0 °C to rt 5) DMSO, reflux

39% (2 steps) 33%

F. L. Bideau et al., Synlett., 800 (2007)

4
toluene, reflux, 5min;
S (COCl)2 TMSCHN2 (2.4 eq.) S
acetone, 0ºC 0ºC to rt, 3h; Rh2(OAc)4 (3 mol%) TMS
NH2
o-xylene, rt, 1h N
92% i-Pr2NEt (5 eq.)
rt, 1d
82% OH
75%
T. Aoyama et al., Tetrahedron, 64, 1753 (2008)
 Fukuyama Group - Group Meeting Problems
07/15/2009
1

DEAD O N
Me SO2N3 N Me S N
1,4-dioxane
10 ºC to rt, 5 h O

76%

X. Xu et al., J. Am. Chem. Soc., 130, 14048 (2008)

2
1) Zn/CuCl
Cl3CCOCl (excess)
BnO Me THF, -5 ºC Me
BnO
54–55%
O O
N S 2) n-Bu3SnH, AIBN N O
H
Boc iPr toluene, reflux Boc
80–85%

J. P. Marino et al., J. Am. Chem. Soc., 114, 5566 (1992)

3
1) DMP, NaHCO3,
CH2Cl2, rt, 3 h
2) BrMg SiMe3 O
O OH THF, 0 °C, 3 h,
OMe 1) Cp2Zr, BF3•OEt2 OH
65% (2 steps)
toluene 3) 1% HCl, MeOH, rt, 4 h, 68%
PMBO OTBS PMBO OTBS 4) C6H6, reflux, 4 h, 100% OPMB
85%

L. A. Paquette et al., Org. Lett., 2, 221 (2002)

4 1) mCPBA
MeO CH2Cl2, rt, 82% CHO
N 2) NaOH
MeOH, rt, 71% CO2Me
N
H
3) TFA HO
N
N CH2Cl2, rt, 52%
MeO2C Cl

G. Lewin et al., J. Org. Chem., 60, 3282 (1995)

 Fukuyama Group - Group Meeting Problems
07/22/2009
1
1) DAST, CH2Cl2
-78 ºC, 86%
2) SeO2, dioxane O
H microwave, 110 ºC
62% F3C
N O
F3C OH
3) H2 (1 atm), PtO2 HN
O Ph
CH2Cl2, 67%
dr 19:1 Ph

Pigza et al., J. Org. Chem., DOI: 10.1021/jo900654y

2
1) CAN(2.2 eq) 1) CAN(2.1. eq)
OMe OH
MeCN-H2O, rt H2O-MeCN(1:1), 0 °C
CO2Me 99% 99% CO2Me

2) Et3N, CH2Cl2 2) K2CO3(5 eq)

0 °C to rt DMF, 100 °C
OMe 94% 70% O

D. Trauner et al., Org. Lett., 7, 5865 (2005)

D. Trauner et al., J. Am. Chem. Soc., 130, 9230 (2008)

O 1) Et3N, TMSCl, DMF 4) TIPSOTf, diisopropylethylamine COOMe

2) n-BuLi, 1,1-dichloroethane CH2Cl2, -78 ºC to rt, 90% Me
anhydrous ether, -30 ºC to rt 5) methyl propiolate, EtAlCl2
3) toluene, ! CH2Cl2, -40ºC to rt, 92 % Me
MeOOC
Me Me 3 steps 69% OTIPS

M. Ihara et al., J. Am. Chem. Soc., 126, 1352 (2004)

4 1) Pd(OAc)2 (2.5 mol%)

dppe (2.5 mol%) OH
CF3CO2H-AcOH H
OH LAH (3 eq) O3 O
reflux, 65% Tricyclic
O THF compound methylcyclohexane
2) OH
0 °C to 60 °C chloroform Me
O (1.2 eq) pyridine (cat.)
O 78% –60 °C
toluene, reflux, 86%
30%

M. Santelli et al., Tetrahedoron Lett., 50, 627 (2009)

M. Santelli et al., Tetrahedoron, 63, 9100 (2007)
 Fukuyama Group - Group Meeting Problems
08/05/2009
1
CrCl3 (20 mol%) Ph
Ph OMe MgCl (4.0 eq) OMe
Me
Ph OMe THF, 0 °C; OMe
I2
Ph
72%
K. Oshima et al., J. Am. Chem. Soc., 123, 4629 (2001)

CO2Me
2 H
1) O2N CO2Me (2 eq.) N CO2Me
CHO
Et2NH, rt O H
O
N 2) TiCl4 (4 eq.), CH2Cl2, rt N H
Ts Ts
58%

K. Harada et al., Heterocycles, 36, 449 (1993)

3
O
Allylamine
CHO t-BuNC Mn(OAc)3•2H2O (4.5 eq.)
AcOH diethyl malonate N
OMe H CO2Et
MeOH, rt; AcOH MeO
OMe evap; CO2Et
90 °C
MeO
59%
L. El Kaim et al., Org. Lett., 9, 4171 (2007)

1) Ac2O-DMSO (1:1), rt
4 O 2) ClTi(Oi-Pr)3 (2.5 eq.) 4) AcOH-H2O (4:1); Me
EtMgBr (5.0 eq.), THF
  
  NaIO4 (3.0 eq.), rt
OMe 0 °C to rt
Me OH O Me OH
3) Me3Al (1.0 eq.), toluene 5) SmI2, (15.0 eq.)
Me OH
-10 °C THF, reflux
O
(60%, 3 steps) (64%, 2 steps)

E. J. Corey et al., J. Am. Chem. Soc., 127, 13813 (2005)

 Fukuyama Group - Group Meeting Problems
09/02/2009
1
mCPBA (1 eq)
CH2Cl2, 0 C; O

N Ph3PAuNTf2 N
(5 mol%)
0 °C

87%
L. Zhang et al., J. Am. Chem. Soc., 131, 8394 (2009)

2 1) cat. SnCl2
n-BuLi acetone HO
THF 2) H2, Pd(OH)2 HO
0 ºC; MeOH, rt CO2Me
O NHBoc
i-BuO O 3) HCl H
O O CO2Me
MeOH-H2O, rt BocN
50% (3 steps)
THF O
0 ºC

77% G. F. Keaney et al., Tetrahedron. Lett., 48, 5411 (2007)

3
O
Ph O
Cl DIBAL (1.5 eq)
TMSOTf Ph
OTBS Me CH2Cl2, –78 °C;
Me
Bn Et3N, THF Ac2O, Py, DMAP CH2Cl2 Bn
O O
0 °C to rt, 16 h –78 to 0 °C –78 °C H H
92% 99% 88%
S. D. Rychnovsky et al., J. Am. Chem. Soc., 126, 15663 (2004)

4
1) i-Pr2NEt (1 eq) 1) Rh2(OAc)4 (3 mol%)
O Cl O CH2Cl2, rt, 74%
2) 6N HCl, 1,4-dioxane O
OH DMF, rt, 65% rt, 93%
OH H
2) isobutyl chloroformate (1 eq) 3) NaH, MeI, DMF, rt
Et3N (1 eq), THF; 73% O
O
CH2N2 (3 eq), Et2O, –15 to 5 °C 4) 1-methylcyclohexene MeO
51% 150 °C, 60%

G. J. Pritchard et al., Org. Lett., 1, 1933 (1999)

 Fukuyama Group - Group Meeting Problems
09/09/2009

1
SMe

H2N NH2
O I Monocyclic Compound O
Ph O
Et3N 1H NMR (DMSO-d6) pyridine O NH
N 2.49 (s, 3H)
Cl Ph
THF, rt 6.29 (s, 1H) reflux
7.45-7.83 (m, 5H) N N SMe
Cl
89% 9.00 (s, 1H) 62%
11.57 (s, 1H)

B. S. Drach et al., Synthesis, 3462 (2006)

2
1) KHMDS(2.05 eq)
THF, –78 to –30 °C;
Br
MeO O
PMB CHO
1) diphenyl phosphite
N N
heat OBn , 84% MeO PMB
one phosphorus
N N atom contained
PMB PMB 2) MeO COCl 2) AIBN(0.5 eq)
Bu3SnH(1.5 eq)
(theoretically MeO Br benzene, reflux, 3 h OBn
0.33 eq) Et3N, CH2Cl2 65%
rt, 2 h, 92%
A. Couture et al., J. Org. Chem., 63, 3128 (1998)

3
1)
N
Cl
O 1) TESCl, pyridine, DMAP O
N MeOH, reflux, 52% t-BuOH, 65 °C, 84%
O
2) BrMg 2) Tf2O, DTBMP
DCE, –20 °C to 65 °C; H
THF, –78 °C, 67% aq. KHCO3/Et2O, 80%

L. E. Overman et al., J. Org. Chem., 67, 6425 (2002)

4
OH
Ni(cod)2 H
OHC HO
Ph TMEDA Ph

OHC THF

61%

J. Montgomery et al., J. Am. Chem. Soc., 125, 13481 (2003)

 Fukuyama Group - Group Meeting Problems
09/16/2009

1
t-Bu OH
Si 1) 9-BBN, THF;
OBn t-Bu
H2O2, NaOH
AgOCOCF3 (1 mol%) 75% HO
monocyclic compound
H
toluene, 50 °C (except for Bn Group)
2) PhMe2COOH, KH
18-crown-6
65% THF, 0 to 50 °C;
TBAF
57%

K. A. Woerpel et al., J. Org. Chem., doi:10.1021/jo901843w

2
1) (R)-phenylglycinol 1) toluene
toluene, reflux, 80% 280 °C, 99%
(Dean-stark) (sealed tube)
bicyclic compound H H
(except for Ph group) N
HO2C O 2) KH, PhS(O)OMe 2) Et3SiH, TiCl4 OH
THF, rt CH2Cl2
3) toluene, reflux –78 to 0 °C O Ph
88% (2 steps) 72%

J. E. Resek, J. Org. Chem., 73, 9792 (2008)

3
1) ClCH2Si(Me)2O-i-Pr
Mg, THF, –5 °C ; OH
4) p-NsCl, pyridine
ClCO2Me CHCl3, 25 °C, 70% MeO2C
bicyclic N Br
compound
N 2) H2O2, KF, KHCO3 5) NBS, THF/H2O
THF/MeOH, rt rt, 69% CH2Op-Ns
3) h! (300 nm), acetone, rt
19% (3 steps)

G. R. Krow et al., Tetrahedron, 56, 9227 (2000)

G. R. Krow et al., Org. Lett., 4, 1259 (2002)

O 1) toluene H
110 °C, 98% O
2) vinyllithium
OTMS THF H OH
–78 °C to rt;
sat. NaHCO3(aq.)
69%
H. W. Moore et al., J. Org. Chem., 63, 6905 (1998)
 Fukuyama Group - Group Meeting Problems
10/13/2009
1
4) 1O2, MB#, h$ #MB = Methylene Blue
1) n-BuLi (1.5 eq.), THF CH2Cl2 (Photosensitizer)
0 °C, 20 min; 0 °C, 2.5 min;
Me Ac2O (1.0 eq.)
"-spiroketal H
Br pyridine, 7 min, rt, 41%
5 min, 89% "-lactone O
intermediate Me
O 2) AD-mix-! (1.0 eq.) (after 5) mCPBA (1.5 eq.)
NaHCO3, CH2Cl2 O O O
MeSO2NH2 (1.0 eq.) the forth step) H OH
t-BuOH-H2O 0 °C to rt, 8h, 80%
0 °C, 40h, 71% 6) TiCl4 (1.0 eq.)
3) H2, Pd/CaCO3/PbO CH2Cl2, –50 °C, 80%
EtOAc, 10h, 95%
G. Vassilikogiannakis et al., Org. Lett., 11, 4556 (2009)

2
#
1) O C C C O (4 eq)
S CH2Cl2
–78 ºC to 25 ºC 1) H2, Pd/C
NH 72% EtOH, rt
Et N
O2N
2) LiAlH4 (2 eq) N
2) toluene H
120 ºC (sealted tube) THF, 0 ºC; Et
66% silica gel, rt
# 35% (2 steps)
Theoretically 1 equivalent
A. Padwa et al., J. Org. Chem., ASAP (Dol: jo901336z)

3
1) H2, Pd/C, toluene, 90%
2) NaBH4, MeOH Dowex 50W-X4
O OHC
Et3N 10 °C, 68% LiBr, H2O O
C10H8O4
CH2Cl2 3) NaH, BnBr, TBAI MeCN BnO OBn
AcO O
THF, 77% HO
60% 88%

G. K. Trivedi et al., J. Org. Chem., 69, 967 (2004)

4 1) Mg (2 eq), THF;
Cl
CO2, 68%
Cl A (C10H16O4)
Et 2) ethyl chloroformate containing one olefin
Cl Et3N, CH2Cl2
O
SPh
N PhS
A N

cholorobenzene
N Me 135 ºC
H N
33% H

E. L. McCaffery et al., J. Organomet. Chem., 8, 17 (1967)

P. Magnus et al., J. Am. Chem. Soc., 105, 4739 (1983)
 Fukuyama Group - Group Meeting Problems
10/21/2009
MeO OTMS
1
OH MeCN, rt 1) i-PrNH2
(o-silylation); MeCN, rt
evap.; 89%

OCO2Me 2) mCPBA
O CH2Cl2
S(O)Ph –78 to –35 °C
85%
Tf2O, 2,4,6-collidine
MeCN, –40 °C

73%
1) TFAA O
CH2Cl2, 0 °C
82% O O
C26H20O4S
2) TFA
CH2Cl2, 0 °C
87% O

Y. Kita et al., Angew. Chem. Int. Ed., 46, 7458 (2007)

2 1) Cp2ZrBu2
–78 to 20 °C, 1.5 h; Cp2ZrBu2 Cl
CuCl (0.1 eq.) –78 to 20 °C, 1.5 h;
3,4-dichlorobutene; CuCl (0.1 eq.) H
3M HCl, 83% 2,3-dichloropropene;
OBn H
MeO 2) NaOMe, DMF 3M HCl
rt, 66% 84% MeO

P. Hermann et al., J. Org. Chem., 73, 6202 (2008)

3
O
O NaClO2 Pd(OAc)2
OHC 1) NaBH4, CeCl3, OTBS NaH2PO4 Cu(OAc)2
OMe ZnCl2 O
MeOH, –78 ºC 2-methyl-2-butene NaOAc, O2 H H
O O
benzene 2) DMAP, Ac2O, 3M LiClO4 THF-t-BuOH-H2O DMSO O
TMSO rt pyridine, rt EtOAc rt 80 ºC O
0 ºC to rt H
71% 87 % in 2 steps 98 % 78 %
87%

Stephen P. Waters et al., Org. Lett., 2009, ASAP (doi: ol902154p)

 Fukuyama Group - Group Meeting Problems
10/31/2009
1
OH
CpRu(PPh3)2Cl (10 mol%)
OH NH4PF6 (20 mol%) O

100 °C O

OH 71%

B. M. Trost et al, J. Am. Chem. Soc., 114, 5476 (1992)

2
O3 CO2Me
O CH2Cl2-MeOH O
OBn –78 °C; O OBn
sunlight;

O O Me2S HIO4, MeOH O O

54% (2 steps)
dr = 4:1
A. J. Herrera et al, Synlett, 1851 (2007)

3 O
O O
O
S OH 1) p-AcNHC6H4SO2N3
O Et3N, MeCN, 100% h! (>290 nm) S O
O MeCN
O xylene 2) Rh2(OAc)4 (1 mol%) O
t-Bu2Si O reflux benzene, reflux, 88% O
69% t-Bu2Si O
88%

M. J. Porter et al., Org. Lett., 10, 5477 (2008)

N Cl
4 Bn N
N
Ph
(10 mol%) O
O OH
Br Et3N (1 eq.)
Ph O
H + Ph
toluene Ph
OH Ph
25 °C
OH
75%
83% ee

T. Rovis!
et al., J. Am. Chem. Soc., 126, 9518 (2004)
 Fukuyama Group - Group Meeting Problems
12/05/2009 OMe

1 OSiMe3 O OMe O
Me OMe O
AgSbF6 (10 mol%) TfOH O
A
CH2Cl2 N
N DCE CO2Me
CO2Me 40 ºC to rt; rt
Et3N MeO2C
58%
O
O H
O
O
Sc(OTf)3 1) LiOH H O
TFAA H2O/THF, rt O
A Br O
CH2Cl2 2) NBS
rt; NaHCO3 N Me
Et3N CH2Cl2 CO2Me
0 ºC to rt
51% 63% (2 steps)
J. A. Porco, Jr. et al., Org. Lett., 9, 4983 (2007)
O
2 Me
1) 2) DMAP (20 mol%) 4) O
AcO SiMe3 !!
!!CH2Cl2 NC H
Et3N S N CO2Me
50 °C, 92% O H
CN
O MeO2C O
MeO2C O Pd(dba)2 (5 mol%) 3) toluene, 150 °C toluene, 50 °C
N L1 (10 mol%) microwave 59% O
Me toluene, 60%, 95%ee 42% N
Me
N
P
O O

J. Patrick et al., Org. Lett., 11, 3782 (2009)

L1

3
O
SiMe3
SiMe3 Me
Me3Si MgBr
THF, –60 °C;
ZnBr2(1.2 eq) OSiMe3
–60 °C to rt

89%
I. Marek et al., Org. Lett., 7, 5313 (2005)
1)
Cl Cl
4 S
O2

Et3N (4 eq)* MeLi, THF, –78 °C;

CH2Cl2, rt SiMe2Ph
Li OH
OH dr = 1.4:1 HO
tricyclic –78 °C to –20 °C;
compound SiMe2Ph
O 2) isomerization*2 ICH2MgCl
dr = 6:1 –78 °C to rt
80% (2 steps)
61%
*theoretically 2 eq
*2BHT (cat.), AcOEt, MW, 120 °C P. Metz et al., Eur. J. Chem., 1144 (2006)
 Fukuyama Group - Group Meeting Problems
12/12/2009
1
1)
1) ethylene (20 atm)
C6H7ClO2 N
Na2CO3 O
Cl Cl C2Cl4, 170 °C, 75% CH2Cl2, 38 °C, 91%
1H NMR (CDCl3) N
!: 1.42-1.52 (m, 2H) O
2) KOH, MeOH 1.69-1.78 (m, 2H) 2) xylene, reflux, 56%
Cl Cl reflux, 41% 3.84 (s, 3H) Cl
3) AG 50W-X8 resin " O
CH2Cl2, rt, 80%
"
Armin de Meijere et al., Org. Synth., Vol. 69, 144 (1990)
acidic resin Armin de Meijere et al., J. Org. Chem., 64, 755 (1999)

2
1) RuCl3•3H2O
NaIO4
Et3N MeCN-CCl4, rt O
bicyclic O
compound xylene
150 °C 2) (COCl)2, rt
O (autoclave) 130 °C Me
3) CH2N2, Et2O
Me Cl –10 °C to rt
66% (3 steps) 60%
Me
R. D. Miller et al., J. Org. Chem., 56, 1453 (1991)

3
cyclohexene Ph
O2N CHO
50% NaOH aq Ph
Ph Br Bu4N·HSO4 BF3·OEt2
Ph Br
benzene, rt CH2Cl2, –10 °C O
O2N
44% 65%

K. Isagawa et al., J. Chem. Soc., Perkin Trans. I, 2283 (1991)

X. Huang et al., Adv. Synth. Cat., 351, 135 (2009)

4
O
N2 TIPSOTf, i-Pr2EtN h# (300 nm) TMSCHN2
O
Et2O-hexane benzene, rt CH2Cl2, rt;
0 °C to rt 1 M HCl aq.
89%
79% 69%

R. L. Danheiser et al., Org. Lett., 4, 2465 (2002)

 Fukuyama Group - Group Meeting Problems
01/27/2010
1

*IPrAuNTf2 (5 mol%) O *IPr =

Ph O rt; concentration; i-Pr i-Pr
+ Ph N N
Me OEt
TsOH (20 mol%) HO Me
acetone-H2O (2 mM), rt
i-Pr i-Pr
93%
L. Zhang et al., J. Am. Chem. Soc., 130, 6944 (2008)

EtO2C CO2Et TsN3 EtO2C CO2Et

CuI (cat.), Et3N

CHCl3-H2O, rt NHTs
89% O

S. Chang et al., J. Am. Chem. Soc., 127, 16046 (2005)

3
O Ph ( 1.1 eq.) O
nBuLi ( 1.05 eq.)
PtCl2 (cat.)

THF toluene Ph
–30 °C to –10 °C 110 °C

70%
59%

C. Fehr et al., Org. Lett., 9, 1839 (2006)

4
O
OTBS PtCl2 (5 mol%) O OTBS
O CO* (1 atm)
O
N toluene, 80 °C
N
Bn Bn H
Me Me
88%
* ligand
L. Zhang et al., J. Am. Chem. Soc., 129, 11358 (2007)
 Fukuyama Group - Group Meeting Problems
02/06/2010
1
Ph Ph O
O I2 (1.5 eq.)
+
Ph THF, rt
CHO Ph
94%

N. T. Patil et al., Euro. J. Org. Chem, 2009, 5178 (2009)

2
1) p-anisaldehyde (1.0 equiv)
CH2Cl2, rt; MgSO4; A (1 equiv)
filtration; evaporation; TFA (3.0 equiv)
mCPBA (1.0 equiv) CH2Cl2, rt;
OH CH2Cl2, 0 °C to rt evaporation; MeO2C Bn
A (MeO)3C Bn
t-Bu NH2 2) NH2OH·HCl (2.0 equiv) Et3N (6.0 equiv) OH
(3.0 equiv)
MeOH, rt AcCl (2.7 equiv)
58% (2 steps) CH2Cl2, –78 °C;
HCl, MeOH, reflux

80%, 96% ee
M. Breuning et al., Org. Lett, 11, 4032 (2009)

3 1) Ph
O N O
N N
CH2Cl2, rt
Me Me
O Me 61% (2 steps) OMe O Me
H 2) NaOAc, DMF H
OHC Me OHC
O 100 ºC, 69% MeO O
Me H Me H
3) CH(OMe)3
H p-TsOH•H2O H
AcO MeOH, rt AcO
H 4) PhI(OAc)2 H
CH3CN-H2O, 0 ºC
64% (2 steps)

M. D. Shair et al., J. Am. Chem. Soc., 132, 275 (2010)

OH H3C PPh3Br (4.0 eq) MeO2C

MeO2C CO2Me CO2Me
O t-BuOK (4.5 eq) N
NH C10H11N Ph
Ph N THF, 0 °C, 3 h DMSO, rt, 3 h
Ph 88% 70% H

A. K. Yudin et al., Org. lett., 12, 240 (2010)

 Fukuyama Group - Group Meeting Problems
03/02/2010
O
1 TsNHNHTs
DBU
Br
A
THF

94% LHMDS
THF, –78 ºC;
A PhNTf2, DMPU O
In(OTf)3 (10 mol%) –78 ºC to rt; toluene
OH
toluene KOt-Bu, –78 ºC 60 ºC, 1 h

87% 75% quant.

T. Fukuyama et al., Org. Lett., 9, 3195 (2007)
T. G. Minehan et al., Org. Lett., 10, 5091 (2008)
2
Pd(OAc)2 (10 mol%)
O O Cu(O2CiPr)2 O
Me Mg(ClO4)2 MgI2 CO2Me
Me
Me OMe
DMSO CH3CN Me
65 °C 40 °C
H
92%, dr = 10 : 1 86%

T. H. Lambert et al., J. Am. Chem. Soc., 131, 2496 (2009)

3
PhS CO2Me
SH cat. Et2NH
O CH2Cl2, 0 °C to rt; MeO2C CO2Me
N CO2Me
EtO CN cat. TiCl4 PhCl, MW, 150 °C
cat. BF3•OEt2 N
O A, MW, 0 to 80 °C 77% Ph

60%
N Ph

A P. Wipf et al., Tetrahedron Lett., 50, 6810 (2009)

4
1) CO(CO2Et)2
O (1 eq) A, CH2Cl2
Sn-Hex –78 °C to rt; NHBoc
KOtBu THF, reflux
N N N A
THF CO2Et P(OEt)3 CO2Et
PPh3 2) mCPBA (1.6 eq)
reflux BuLi (1.5 eq) Et3N, rt
CH2Cl2
59% 85%
50% (2 steps)
A. Armstrong et al., Angew. Chem. Int. Ed., 46, 5369 (2007)
 Fukuyama Group - Group Meeting Problems
04/07/2010
1
Ph3PAuSbF6
OPiv (5 mol%)

MeCN, –20 °C; O

H2O, rt
H
88%
98% ee 96% ee

F. D. Toste et al., J. Am. Chem. Soc., 127, 5802 (2005)

2
LDA (s)-trioxane N3
THF, –78 °C; BF3•OEt2 SbCl5
CO2Me
HO CO2Me
SiMe2Ph Trisyl azide CH2Cl2 CH2Cl2
–78 °C to rt –50 °C –50 °C Me

76% 91% 96%

dr: >30: 1
J. S. Panek et al., J. Org. Chem., 56, 7341 (1991)
J. S. Panek et al., J. Am. Chem. Soc., 124, 11368 (2002)

Rh(PPh3)3Cl (10 mol%)

O
(20 mol%) O
N NH2
C4H9
1-Hexene-toluene, 150 °C

98%

Chul-Ho Jun et al., J. Am. Chem. Soc., 121, 880 (1999)

OHC
4 OMe
(5 eq.) OMe
Me TMSOTf (5 eq.)
DIEA (3.5 eq.)
N N
CO2Me CO2Me
CH2Cl2
Me –78 °C to rt Me

O 69 % O

J. A. Porco, Jr. et al., Org. Lett., 9, 4983 (2007)

 Fukuyama Group - Group Meeting Problems
04/14/2010
1 O
TIPSOTf
Br
Et3N
OH OPh benzene
i-Pr2NEt rt;
OH
n-Pr NH n-Pr N
CH3CN LiAlH4
0 ºC Et2O
Ph Ph
0 ºC to rt
60%
79%

Y. Blanche et al., J. Org. Chem., 62, 8553 (1997)

2
CO2Me
Me OH Me
PhSCl 1) NaCH(CO2Me)2
Et3N Me O
THF, rt
O
CH2Cl2 2) P(OMe)3
H –78 °C to rt NaOMe (cat.) H
MeO MeOH, reflux
quant. 78% (2 steps) MeO

H. J. Altenbach et al., Tetrahedron Lett., 27, 1561 (1986)

3 1) O
H
N O
O H2N OMe O
OTBS
O HO
N N AcOH o-Cl2C6H4 N
H N THF, 35 °C 180 °C
O
N 2) TsCl, Et3N EDCI, DMAP 71% N
Bn CH2Cl2 CH2Cl2, rt
0 °C to rt Bn H CO2Me OTBS
81% (2 steps) 74%
D. L. Boger et al., J. Am. Chem. Soc., 132, 3009 (2010)

4 1)
H Ph
Ph 3) LDA (1.10 eq.),
N O PhNO (1.05 eq.)
H B Tf2N THF, –78 °C, 3h; 6) DMP (1.2 eq.)
o-tol H2O; evaporation; THF-CH2Cl2 (1:1)
(10 mol%) LiOH (5.0 eq.) O
0 °C to rt, 3h;
O 1,3-cyclohexadiene dioxane-H2O, rt, 24h; filtration; O
H
neat, 4 °C, 15h HCl(aq.), 68% evaporation;
OCH2CF3
H
2) NaOMe, MeOH 4) m-CPBA (1.1 eq.) MeMgBr (3.0 eq.)
22 °C, 15 min NaHCO3 (3.0 eq.) THF-Et2O Me
90%, 99% ee CH2Cl2, 0 °C, 3h, 85% 0 °C, 20 min;
5) LiOH (1.5 eq.) 4M H2SO4
THF-H2O (2:1) 0 °C to rt, 30 min
rt, 8h, 91% 65%, 99% ee
E. J. Corey et al., Org. Lett., 12, 1836 (2010)
 Fukuyama Group - Group Meeting Problems
04/20/2010
1
O Cl
OTIPS 1) 50% NaOH aq. Et
BnEt3NCl
Et CHCl3, rt

2) AgBF4
MeCN, reflux
OMe
81% (2 steps) OMe

G. West et al., Org. Lett., 9, 3789 (2007)

2
1) MVK, NaOMe
CHO MeOH
0 °C to rt, 42% hν *
C17H20 H
2) LiAlH4 MeCN Ph
Ph AlCl3
Et2O, 0 °C, 51% 40-60%
* 450W Hanovia medium-pressure lamp
and Vicor filter

P. S. Mariano et al., J. Am. Chem. Soc., 98, 5899 (1976)

3
1) Cl(CH2)3OH, Et3N
toluene, reflux;
NaBH4, EtOH O R
0°C, 70% O R
Cu(acac)2 (5 mol%)
C13H19N3O4 + O
2) EtO2CCH2COCl toluene, reflux O N
N N
Et3N, 60%
3) trisyl azide, Et3N
MeCN, rt, quant. 54% 23%
dr = 57:43
R= CO2Et
J.B. Sweeney et al., Org. Lett., 7, 2075 (2005)

4
NH2 CHO 1) MeCN, rt;
N
TFAA, 0 ºC;
OHC NaBH3CN, rt, 66% O
+ O
CO2i-Pr 2) NaOH, EtOH, 75 ºC
MeO N 88% N H
MeO
OMe Me TMS 3) K3Fe(CN)6, NaHCO3 OMe Me
t-BuOH-H2O, rt, 92%

E. J. Corey et al., J. Am. Chem. Soc., 121, 6771 (1999)

 Fukuyama Group - Group Meeting Problems
04/28/2010
1
O
O CHO
NH2 O
1) MeOH, rt, 82% O
+ O
2) 85% H3PO4 N N
N C HO2C 100 ºC, 72% H
CO2Et O

A. V. Ivachtchenko et al., J. Org. Chem., 71, 9544 (2006)

2 O
BocHN 1) A, CHCl3, rt 1) TFA, CH2Cl2, 0 °C O
SH
C24H38N2O5 MeHN OBn
2) n-Bu3SnH (2.5 eq.) N
2) cyclopentadiene
AIBN (1.0 eq.) HCHO, H2O Me O
toluene, 100 °C 3) Et3SiH, TFA
CHCl3, rt
62% (2 steps) (isolated as a HCl salt)
CN
OBn A 52% (3 steps)
O

S. J. Danishefsky et al., J. Am. Chem. Soc., 132, 4098 (2010)

3
1) CeCl3, CH2=CHMgBr
O THF, –70 °C;
AcOH, –70 to –20 °C
Boc aq. HCl, 60 °C; evap;
83% HN
N
HO2C H Cl
2) NaBH4, CeCl3·7H2O (CH2O)n, MeCN-H2O, 70 °C N
N CO2t-Bu MeOH-THF, 0 °C
H O
CO2t-Bu 86% 93%
OH

L. E. Overman et al., J. Am. Chem. Soc., 132, 4894 (2010)

4
Grubbs 2nd

TMSOTf, Et3N O
OH
O CH2Cl2, –78 °C; CH2Cl2, reflux; Ph O
CO2Et
PhCH(OAllyl)2 cat. Rh2(OAc)4, rt; O
N2 BF3·OEt2, –78 °C NaBH3CN, AcOH EtO2C
THF, 0 °C to rt
92%
26%
D. J. Hodgson et al., Org. Lett., 10, 5553 (2008)
 Fukuyama Group - Group Meeting Problems
05/01/2010
1
1) Ph3P CH2
COOH
THF, 0 °C Ni(COD)2 (4 mol%) O
N Me
O H (20 mol%) 77% PPh3 (8 mol%)
Ph
Me O CH3CN, 25 °C
Me H 2) LDA, THF
S O Ph
Me Ph –78 °C;
PhCOCl 94%
CHCl3, 0 °C
47%
68%
J. S. Johnson et al., Org. Lett., 8, 573 (2006)

2
OTIPS PhI(CN)OTf O
(1.2 eq.) KF, Al2O3
n-BuLi (2.1 eq.) CH2Cl2, –40 °C; THF
THF, –78°C; evaporation; –78 °C to r.t.;

MeO n-Bu3SnCl (2.0 eq.) LHMDS air MeO

–78 °C (1.3 eq.) N
DME, –40 °C 57%
MeO NHTs 77% MeO
64%
K. S. Feldman et al., J. Org. Chem., 67, 8528 (2002)

3
O
O H2NSO3-CH2CCl3 , MgO
Cl3C
[Rh(CF3CONH)2]2 (4 mol%) O
PhI(OAc)2 TFA O
O O
S
toluene, 0 °C to rt, 6 h DCM, 0 °C, 15 min N
PMP O
80% 90%
PMP

S. Hanessian et al., Org. lett., 12, 1816 (2010)

4
1) NIS (2 eq.)
1) t-BuNC allyl alcohol
N O THF-H2O acetone, rt
reflux, 100% 72%
Ph O
O
2) FeSO4 2) Pd(PPh3)4 (10 mol%) O N
NaNO2 Et3N Ph t-Bu
AcOH-H2O MeCN-THF (3:1)
rt, 92% reflux, 51%

S. Z. Zard et al., Org. Lett., 12, 416 (2010)

 Fukuyama Group - Group Meeting Problems
05/15/2010
1
[(MeCN)4Cu]BF4 O
OTBS N2 (5 mol%) Ph CO2Et
CO2Et
+
MeOC Ph CH2Cl2
N2 rt O

61%

Jose Barluenga et al., Angew. Chem. Int. Ed., 48, 7569 (2009)

1) BrMg Me
2 THF, 0 °C; Ph
O 1 N HCl
78% TMSCl, Et3N O
H 2) NaH, THF, rt; benzene, rt;
Ph 6 N HCl
NO2
O
–40 °C; 91%
1 N HCl
68%

J. L. Duffy-Matzner et al., Tetrahedron Lett., 50, 6446 (2009)

3 Br

O pyrrolidine Tf2O
Et3N NaH collidine H
O H
reflux THF CH2Cl2
microwave O
46% O
quant.
48%

N. Maulide et al., Angew. Chem. Int. Ed., 49, 1583 (2010)

4
TES Et3N•Mo(CO)5 s-BuLi* Pd(PPh3)4 TES
(20 mol%) Et2O-pentane (3 mol%)
H n-Bu3SnOTf* –60 ºC; CO (1 atm) H
HO O O O O
Et3N-Et2O RLi*,Cu(1-pentynyl)* i-Pr2NEt-MeOH-THF
rt Et2O, –78 ºC to rt; reflux
I2*, –78 ºC R
63% 91%
66%

* theoretically 1 equiv.
R=
P. J. Kocienski et al., J. Org. Chem., 68, 4008 (2003)
 Fukuyama Group - Group Meeting Problems
06/02/2010
1
HSi(i-Pr)3
NH2-NMe2 [RhCl(COD)]2 (10 mol%)
TpRuCl(PPh3)2 (10 mol%) P(Oi-Pr)3 (20 mol%)
MeO C9H9ON MeO Me
1,4-Dioxane, reflux ethylcyclohexane
160 °C
88%
75%
S. Murai et al., Organometallics, 21, 3845 (2002)
N. Chatani et al., Bull. Korean Chem. Soc., 31, 582 (2010)

2
3) (t-Bu)2P(o-biphenyl)AuCl
OTES 1) (COCl)2, DMSO (10 mol%)
CH2Cl2, –78 to –50 °C; AgSbF6 (5 mol%) O
OPh Et3N, –78 to 0 °C, 86% i-PrOH, CH2Cl2, rt, 78%
Me
2) O O 4) O3, MeOH-CH2Cl2, –78 °C; O
Me
OTES OP P OMe Me2S, –78 to –23 °C; OP
Me
OMe DBU, MeCN, 0 °C, 75%
N2
(P = TBDPS)
K2CO3
MeOH, rt, 90% L. E. Overman et al., J. Am. Chem. Soc., 132, 7876 (2010)

3 O
PtCl2 (10 mol%)
CO* (1 atm)
OH
Ph O toluene, 60 °C;
OAc silica gel
Ph O O
78%

*: Ligand

X. She et al., J. Am. Chem. Soc., 132, 1788 (2010)

4
O
1) TMSC(Li)N2, THF
OTBS O –78 °C

Me O 2) 10% citric acid Me

O 81 % (2 steps)
OTBS

T. Shioiri et al., Tetrahedron Lett., 41, 6859 (2000)

 Fukuyama Group - Group Meeting Problems
06/15/2010
1 1) Troc
N N
O OMe Troc MeSCH2CO2Et* O OMe
Me TFA, rt SO2Cl2*, proton sponge Me
N 95% CH2Cl2, –78 °C; N
NH
N 2) Zn dust Et3N, –78 °C to rt N
Ts AcOH Ts
MeS O
88% 66%
* these reagents are reacted
in advance

S. J. Danishefsky et al., Angew. Chem. Int. Ed., 46, 1448 (2007)

2
O
OTBDPS 1) Rh2(OAc)4, PhCF3 H
100 ºC, 73% 3) DMP, CH2Cl2, rt, 92%
N2 O H
O
OPMP 2) (NH4)2Ce(NO3)6 4) 2-methyl-2-butene O
NaH2PO4, NaClO2 OTBDPS
O O pyridine, MeCN-H2O
0 ºC, 91% t-BuOH-H2O, rt CO2Me
5) CH2N2, Et2O, 0ºC
85% (2 steps)

S. Hashimoto et al., Angew. Chem. Int. Ed., 45, 6532 (2006)

3
Ph Ts
TsNClNa
NBS (cat.) MgBr SnCl4(2 eq) N
O

O OMe MeCN, rt Et2O CH2Cl2

–30 °C to rt rt Ph
61%
61% 60%

A. Armstrong et al., Org. Lett., 7, 1335 (2005)

4 O

H
1) N-aminophthalimide*
LTA*, CH2Cl2, rt, 51%
Ph
Ph
2) hydrazine hydrate* CH2Cl2, MgSO4, 0 °C;
(E)-stilbene EtOH, 45 °C, 75% evaporation;
PhH, reflux, 42%
(* theoretical amount: 1 eq)
A. Eschenmoser et al., Org. Synth., Vol. 55, 114 (1976)
A. Padwa et al., J. Am. Chem. Soc, 115, 2637 (1993)
 Fukuyama Group - Group Meeting Problems
07/07/2010
1
O O OTBS
MeOTf, MS4A
MeO EtCN, rt; MeO
OTBS Ph
O BnMe3NCN N
Ph 0 °C to rt Me
N O
40%
E. Vedejs et al., J. Org. Chem., 62, 8506 (2007)

2
SO2Ph

1) AlCl3, CHCl2OMe 1) Raney-Ni, H2 MeO O

MeO CH2Cl2, 0 °C SO2Ph THF, reflux
CO2Me
toluene N
2) NH2OH·HCl 2) n-Bu3SnH, AIBN MeO
MeO NaOAc, MeOH, rt reflux toluene, reflux H

80%
77% (2 steps) 57% (2 steps) O

A. Padwa et al., J. Org. Chem., 74, 3491 (2009)

3
PhMgBr, ZnCl2 toluene-d8 NH
N3 cat. Pd(PPh3)4 reflux;
H CN
Me THF TMSCN Me
MsO –50 °C to rt CH2Cl2
0 °C to rt
85%
50%

K. S. Feldman et al., J. Am. Chem. Soc., 127, 4590 (2005)

4
Ph OMe BF3•Et2O (1 eq.) (COCl)2 1) PhMgBr (2.5 eq.) Ph
O Et3SiH (2 eq.) DMSO THF, rt
pyrrolidine
derivative
CH2Cl2 CH2Cl2, -78 °C; 2) BF3•Et2O (4 eq.) MsN
N
Ms reflux Et3N, 0 °C; CH2Cl2, 0 °C Ph
H
Ph3P=CHCO2Et
76% 71% (2 steps)
76%

M.-Y. Chang et al., Org. Lett., 12, 1176 (2010)

 Fukuyama Group - Group Meeting Problems
07/14/2010
1 3) MoO2Cl2 (1.5 mol%)
1) Thioacetic acid aq. H2O2
PPh3, DIAD acetone/H2O, rt O
THF, rt 47% (3 steps)
OH
Br
2) 4) PtCl2 (10 mol%) S
ClCH2CH2Cl
K2CO3, MeOH 90 ºC, 52%
rt

P. W. Davies et al., Angew. Chem. Int. Ed., 48, 8372 (2009)

2
Rh2(OAc)4
N2 toluene, 60 °C;
O
reflux;
N O
CO2Me + Ph Ph
DDQ, rt
N CO2Me
84%

H. M. L. Davies et al., J. Am. Chem. Soc., 130, 8602 (2008)

3 I H
N CO Et
EtO2C N 2
DEAD NH2
H
CH2Cl2, 0 °C Pd(OAc)2, K2CO3, LiCl
toluene, 100 °C
quant. N H
H
93%

K. V. Radhakrishnan et al., J. Am. Chem. Soc., 131, 5043 (2009)

4 3) LDA (1.2 eq.), THF

–78 °C, 30 min;
pyrrolidine 1H-NMR 1,2-dibromoethane
(1.5 eq.) –20 °C, 2.5h, 98%
cyclopentadiene (CDCl3, 1) methyl acrylate 4) (PhSe)2, NaBH4 Me Me
O
(2.5 eq.) 300 MHz) neat, 80 °C, 12h EtOH, reflux, 2h, 93%
Me Me δ = 2.19 ppm
MeOH (s, 6H) 2) H2, cat. PtO2 5) NaIO4, i-PrOH-H2O
12 min, rt; δ = 6.45 ∼ CH2Cl2-MeOH rt, 30 min; NaHCO3 H
AcOH (1:4) reflux, 99% CO2Me
6.53 ppm
86% (2 steps) 6) toluene, 140 °C
(m, 4H) dr = 1:1 24h, 94%

R. D. Little et al., J. Org. Chem., 49, 1849 (1984)

V. B. Birman et al., Org. Lett., 12, 3472 (2010)
 Fukuyama Group - Group Meeting Problems
07/21/2010
1
1) TiCl4, NaHCO3
EtNO2, —78 °C, 46%
2) [VO(acac)2] OH
OH TBHP, NaHCO3
BnO HO
OBn CH2Cl2, rt, 47%
+ O
O
3) TsOH·H2O OBn
O OTES MeOH, 40 °C, 67%
OMe

H. Watanabe et al., Angew. Chem. Int. Ed.,49, 5527 (2010)

2
Me
1,2-dibromoethane
O O K2CO3 SnCl4·5H2O
N DMF, rt
H xylene, 120 °C O N
OMe
99% 88% OMe

Q. Liu et al., Angew. Chem. Int. Ed., 46, 1726 (2007)

3
O 1) (MeO)3CH, TsOH, rt, 99%
CO2Et
2) TMSOTf, i-Pr2NEt 4) MeCN, TMSOTf
CH2Cl2, 0 °C to rt, 98% MeNO2, –40 °C, 95% N
C17H23NO5S Me
N 3) N2CHCO2Et, Cu(TBS)2* 5) SeO2 (5.0 eq) N
Ts CH2Cl2, reflux, 8 h, 90% dioxane, reflux H
24-40 h, 92%
* t-Bu
N
O
Cu
O
N
t-Bu
B. L. Pagenkopf et al., Org. Lett., 12, 3168 (2010)

4
MS 4A
TFA-CH2Cl2
N rt; evap.; hν (254 nm) LAH
H N
O NaHCO3 benzene, rt THF, reflux H N
Boc N OBoc CH2Cl2, rt
76% 95%
74-98%
J. Aubé et al., Org. Lett., 5, 2577 (2002)
 Fukuyama Group - Group Meeting Problems
08/04/2010
1 1) mCPBA
CH2Cl2
HO reflux HO
[Pt(C2H4)Cl2]2 (10 mol%) 88%
toluene 2) LiAlH4 HO
reflux THF
reflux
97% 82%
J. K. Snyder et al., Org. Lett., 4, 2731 (2002)

2
Me H Me H
Me Me
Me CHO 1) A, p-TsOH, MgSO TIPSO
4 TIPSO H H
CH2Cl2, –78 to –20 °C 3) hν, dioxane OH
Me H H
HO
O
2) cat. SnCl4, CH2Cl2 4) KOH, MeOH
–78 °C to rt 55% (2 steps) A
TBDPSO 84% (2 steps)
HO TMS

L. E. Overman et al., J. Org. Chem., 74, 5458 (2009)

3
1) CSI, CH2Cl2, 0 °C 1) Boc2O, DMAP O
OTBDMS 2) Red-Al, toluene, –78 °C CH3CN, 99%
C13H16N2OSi NH
PhMe2Si 3) Et2AlCN, toluene, 50 °C 2) Pd/C, H2
AcOH, 75% PhMe2Si
43% (3 steps) NHBoc

K. A. Woerpel et al., J. Org. Chem., 74, 6915 (2009)

4
Fe(CO)5
OBn 1) TsNHNH2 hν, THF, rt
MeOH, rt (under CO gas);
Tricyclic Compound O
(except for Bn group)
2) K2CO3 DBU, rt
O toluene, 130 ºC BnO
82% (2 steps) 31% (47% SM rec.)

D. F. Taber et al., J. Am. Chem. Soc., 132, 11179 (2010)

 Fukuyama Group - Group Meeting Problems
09/04/2010
1
1) Br(CH2)3PPh3Br
NaH (2 eq), DME 3) Zn, AcOH O
O
70 °C, 82% rt, 56%
Ar Me
2) CHBr3, NaOH 4) CO (1 atm) Ar
Ar = 4-MeC6H4 BnEt3NCl 5 mol% [RhCl(cod)]2 Me Me
CH2Cl2-H2O 10 mol% DPPP
reflux, 54% p-xylene
130 °C, 82%

M. Murakami et al., J. Am. Chem. Soc., 129, 12596 (2007)

2
HO 1) DAIB, I2, hν Zn
O3, MeOH-CH2Cl2 cyclohexane-CH2Cl2 NaI
–78 °C; Me2S; 15-20 °C, 85% H2O O
TBSO NaBH4 2) MsCl-Py DME H
H O
O –78 °C to rt; 0 °C, 98% reflux
O H+ O
78%
87%
A. Galindo et al., Tetrahedron Lett., 38, 6737 (1997)

3
1) Pd(OAc)2, PCy3
Zn, MS4A O
O Ph DMF 1) HCl, THF
N
100 °C, 78% 1) NaOMe, MeOH, rt 50 °C, 78%
O HO
2) diketene, TMSCl 2) Tf2O, Pyridine 2) Et3SiH
CN CH2Cl2, –78 °C Pd(OAc)2 Ph O
MOMO MeCN, 50 °C
56% (3 steps) dppf, DMF Me
70 °C, 96%

K. Ohe et al., Chem. Commun., 3466 (2009)

4 1) 5% NaOCl* aq.
rt pyridine
SESNH2 reagent A
2) SOCl2, reflux rt
(C5H15O2NSSi) 78% (2 steps) (C10H26O4N2S3Si2)

* theoretically 2 equiv.

H reagent A H
O toluene, 95 °C; O O
O
NBoc NaBH4 NBoc
H MeOH, 0 °C H
SESHN
S. M. Weinreb et al., J. Am. Chem. Soc., 121, 9574 (1999)
 Fukuyama Group - Group Meeting Problems
09/11/2010
1
SO2N3 CuI (0.1 eq), Et3N
O O PhO2SN CO2Et

Me OEt THF, 40 °C
Ph O Me
80%

Y. Shang et al., J. Org. Chem., 75, 5743 (2010)

2
N3
1) benzene
reflux N C2H5
C2H5 N MeO2C
2) hυ (pyrex)
N O MeOH, rt CO2Me
CO2Me 75%

A. G. Schultz et al., J. Org. Chem., 45, 2041 (1980)

3
LDA
O LiBr, THF, –78 °C; THF, –78 °C;
Ph3P CO2H
Ph H PhLi, O TMSCl
–78 to 70 °C Ph
Br O
–78 °C to rt 80%
57%

D. M. Hodgson et al., Org. Lett., 12, 4204 (2010)

4 1) (TMS)3SiH
hexane
sunlamp
N OBn 50 °C, 70 % O

2) 5% HCl
100 %

G. Pattenden et al., Tetrahedron Lett., 34, 6787 (1993)

 Fukuyama Group - Group Meeting Problems
09/15/2010
1
1) PBA∗
1H 1)
CH2Cl2, rt NMR (250 MHz, CDCl3): NH2
90% d = 3.10 (m, 2 H) THF, 0 °C to rt
2.25 (m, 2 H)
N
O 2) HCl aq. 2.10 (m, 2 H) 2) Tf2O, Py.,
CH2Cl2 1.80 (m, 4 H) CH2Cl2, rt Tf
rt 3) toluene, 130 °C
(in a sealed tube)
∗PBA = perbenzoic acid 74% (2 steps)
P. W. Jennings et al., J. Org. Chem., 54, 5186 (1989)
A. Padwa et al., J. Org. Chem., 68, 5139 (2003)

2
La(OTf)3 (0.1 eq)
O 2,6-lutidine (0.05 eq) 1) H2, Pd/C O
LiClO4 (0.75 eq) MeOH, rt
BnO
HO
DCE, 40 °C 2) NaIO4
Me Me
MeCN/H2O
84% 76% (2 steps)

T. H. Lambert et al., J. Am. Chem. Soc., 131, 7536 (2009)

3
LHMDS Mg
THF, HMPA BrCH2CH2Br H OH
OMe –78 °C; NaOH THF, rt; p-TsOH
O O
n-BuI MeOH, rt O acetone
–78 to –20 °C reflux
73% Br O
n-Bu
75% 92% 73%

D. Kim et al., J. Org. Chem., 65, 4864 (2000)

4
1H NMR (400 MHz) 1) mCPBA
Fe(CO)5 CH2Cl2, 0 °C
CO (2 bar) A δ 2.21 (s, 1H) 85%
A O
175 °C B no (s, 1H) signal 2) p-TsOH•H2O
0 < δ < 3.0 CH2Cl2, rt O
β-pinene
77% 99%
(A:B = 1:1)

S. Blechert et al., Synthesis, 607 (1999)

 Fukuyama Group - Group Meeting Problems
09/28/2010
1
Me
1) EtSCH2COCl (1.3 eq.) Me
Ac2O (10 eq.)
benzene, reflux p-TsOH (trace) OAc

H 2) NaIO4 (1.1 eq.) toluene, reflux N O

N MeOH-H2O, rt
PMB PMB
81%
O
90% (2 steps)

A. Padwa et al., J. Org. Chem., 65, 2368 (2000)

2
Bn O MeO2C CO2Me
N CHCl3, rt;
+ MeO2C CO2Me
Cl
H
O N
MeO PPh Me Bn OMe
Me O ,DBU

85%

B. A. Arndtsen et al., J. Am. Chem. Soc., 129, 12366 (2007)

3
1) tBuLi
EtO Et2O, –40 ϒC; EtO
MeO Ph MeO O
Bu3SnCl

PMP 2) mCPBA Ph
MeO O MeO O PMP
DMF, rt

50% (2 steps)

A. J. Frontier et al., J. Am. Chem. Soc., 131, 7560 (2009)

4
B PhS
H
CHO S
O TMS Ph
H Li OTBS H
THF, 0 °C; 2 M LiClO4-Et2O
H
4 M NaOH, rt THF 10 mol% TFA
O O
H –78 °C
OTBDPS 73% OTBDPS
66%
80% TBSO

P. A. Grieco et al., J. Am. Chem. Soc., 120, 5128 (1998)

 Fukuyama Group - Group Meeting Problems
10/06/2010
O
1 CO2Et
LHMDS (2 eq) O
THF, –78 °C; anisaldehyde Ph
O Ar
Tf2O (1 eq); LiOi-Pr (0.1 eq) Cs2CO3
CO2Ph C25H32O4Si O
LHMDS (2 eq); THF acetone CO2Et
Me TESCl –10 °C rt
–78 °C to rt Ph
68%(2 steps) 81%
(Ar = PMP)

D. Lepore et al., J. Am. Chem. Soc., 131, 4196 (2009)

2 ClMgCu
3 NaCN, THF, 45 °C; O
C10H21 C5H11 2 BzCl, 45 °C;
B C10H21
3
H Et2O H2O2, aq. NaOH
–78 °C to rt; 0 to 50 °C C5H11
silica gel (filtration)
83%
80% (crude)
C. G. Whiteley et al., Synthesis, 1141 (1993)

3 Cl
1) CONMe2
HO
O2N NO2 MnO2
O NH
N n-BuOH, reflux, 64% NaCN, Me2NH TBSO
NO2 N
O2 N 2) TBSCl, imidazole,DMF; i-PrOH-THF, rt MeO
EtOH, Me2NH O
MeO 50 to 65 °C, 55% 64%

C. D. Vanderwal et al., Org. Lett., 12, 3093 (2010)

4
1) MeLi (1.05 eq) THF, 120 °C Ot-Bu
1) PhH, reflux O
THF, –78 °C; microwave;
quant TFAA, 82% evap.;
t-BuO Ot-Bu C12H18O4 O
2) NBS, CCl4, rt 2) Li OMe Dess-Martin
83% OMe
C10H18O2 periodinane
CH2Cl2, 0 °C
THF, –78 °C 75% (single
37% (dr = 3:2) diastereoisomer)

F. Serratosa et al., Acc. Chem. Res., 16, 170 (1983)

D. C. Harrowven et al., Angew. Chem. Int. Ed., 46, 425 (2007)
 Fukuyama Group - Group Meeting Problems
10/16/2010

1
1) 1
1) SnCl4 SnCl4 CO2Me
CH2Cl2 CH2Cl2 N
0 °C to rt rt; aqueous workup Bn
OH 78% 78% CO2Me
Cl N
N 2) NaOEt Bn
2) MsCl N
EtOH Et3N 1
O rt CH2Cl2 O
95% 0 °C
34%
W. Zhang et al., Org. Lett., 12, 1696 (2010)

2
1) Br CO2Et
(1 eq) PPh3
CHCl3, reflux 2-ClC6H4CHO
CO2Et
EtO2C PPh3
2) Et3N (2 eq) CH2Cl2 CO2Et
Cl
CH2Cl2, rt; rt
AcCl (1 eq)
79% trans : cis = 10:1
74% (2 steps)
Z. He et al., Org. Lett., 12, 544 (2010)

PhO2S n-C5H11 Br2 (2 eq.) n-C5H11

PhO2S
Br3– salt
H MeCN, rt; aq. Na2S2O3
S
99% ee 62%, 99% ee

S. Ma et al., Angew. Chem. Int. Ed., 46, 4379 (2007)

4 Ti(Oi-Pr)4 (1.5 eq.)

Bn c-C5H9MgCl (3.0 eq.) PPh3, imid. Et
N
Et2O CCl4
Ph H N Ph
–70 to – 40 °C; reflux
Bn
LiO 81%
–40 to 0 °C

73%

M. Takahashi and G. C. Micalizio, J. Am. Chem. Soc., 129, 7514 (2007)

 Fukuyama Group - Group Meeting Problems
11/02/2010
1 PdCl2 (1.0 mol%)
CuI (10 mol%)
K2CO3 (10 mol%) O-p-NO2C6H4
OH Et3N (1.0 eq.) S
S-p-NO2C6H4
DMF, 80 °C
O
60% O

N. Kambe et al., Org. Lett., 10, 2469 (2008)

2
SEMO SEMO
1) CH2N2
O 1) mCPBA, NaHCO3 Et2O, rt
O CH2Cl2, rt, 99% 73% (2 steps) CO2Me

O O 2) Me2CuLi* 2) SOCl2, Py CO2(CH2)2TMS

O(CH2)2TMS THF, –78 °C –25 to –20 °C O
O 82% O
*: theoritically 2 eq.

K. Mori et al., J. Chem. Soc., Perkin Trans. 1, 2923 (1991)

3
OBn
DBU O
O micro wave O
HO
toluene
220°C BnO

81%, dr >98%
L. Barriault et al., Org. Lett., 4, 1371 (2002)

4 O O
KO S O O S OK
O O
benzene*
I AgF
H2SO4, rt;
Reagent A
NO2 KI, H2O, rt H2O, rt

87% 78%
* theoritically 1 eq.
MeO2CN TiCl3 MeO2CN
Reagent A NH4OAc

Et DMSO-THF Et
THF-H2O
TBSO rt rt N
H
94% 89%

V. H. Rawal et al., J. Am. Chem. Soc., 120, 13523 (1998)

 Fukuyama Group - Group Meeting Problems
11/13/2010
1 O O O
CO2Et
N2 N
OTBS EtO SnCl4 H OTMS H
LDA, THF CH2Cl2 toluene N
–78 °C 0 °C rt to reflux H
89% 94% 88%
M. Brewer et al., J. Org. Chem., 74, 8410 (2009)

2
SiPhi-Pr2 (11 eq.)
O
TiCl4 HBF4•OMe2 (9 eq.) H

Ph CH2Cl2 CH2Cl2
reflux rt

25% 59%

H. J. Knolker et al., Angew. Chem. Int. Ed., 38, 2583 (1999)

H. J. Knolker et al., Angew. Chem. Int. Ed., 33, 1612 (1994)

3 Cl

O AlCl3 Na2CO3 O

Cl CH2Cl2 MeOH, reflux; CO2Me

–10 °C to rt 1% HCl aq

75% 76%

O. G. Kulinkovich and V. L. Sorokin, Synthesis, 361 (1994)

4 UV light
(2 kW Hg-vapour lamp; Pyrex filter;
Symantec large-scale
photolysis unit)
1) Dowex 50WX8(H)-resin cat. conc. H2SO4
O 1,2-ethanediol (1.2 eq.) MeOH-H2O (6:1), rt; CO2Me
benzene, reflux, 30h, 90% H2O, reflux, 1h; evaporation;
C10H6Br2O2
2) Br2 (3.2 eq.), 1,4-dioxane 30% aq. NaOH, reflux, 3h;
N2-flow, 10 °C, 6h; conc. HCl, 10 °C; MeO2C
NaOH (5.6 eq.) filtration; evaporation;
MeOH, 10 °C, 4h; Dowex 50WX8(H)-resin, MeOH
reflux, 16h, 75% reflux, 24h, 79%
3) conc. H2SO4, rt, 24h, 98%

T. W. Cole and P.E. Eaton, J. Am. Chem. Soc., 96, 962 & 3157 (1964)
M. Bliese and J. Tsanaktsidis, Austral. J. Chem., 50, 189 (1997)
R. Priefer et al., Synthesis, 98 (2010)
 Fukuyama Group - Group Meeting Problems
12/11/2010
1
1) hν O
N EtOH, rt, 85%
N
N 2) TFA, rt, 80%
O N

M. Ishikawa et al., Tetrahedron Lett., 11, 2329 (1970)

2 • OH
O
I Pd(dba)2 Cl
Me3SiSnBu3 TiCl4 LTMP∗

toluene, 80 °C CH2Cl2 t-BuOMe

–78 °C 0 °C to rt
50%
60% 59 %
∗theoretically 2 eq.

D. M. Hodgson et al., J. Am. Chem. Soc., 129, 4456 (2007)

3
morpholine (2 eq) 1) NaBH4, CeCl3·7H2O O
Dy(OTf)3 (10 mol%) MeOH, 0 °C, 95% OBn
O Cl O
O O N
H MS4A, MeCN, rt 2) NaH, BnBr, DMF TiCl4 (10 mol%) N
0 °C to rt, 84% i-Pr2NEt (1.5 eq) H
CH2Cl2 O
quant
72%

R. A. Batey et al., Chem. Commun., 3759 (2007)

4
OMe
OMe O
O O
TMSOTf (1.2 eq) H
O
MeO MeNO2, reflux
Me MeO
O Me
70%

E. Fillion and D. Fishlock, J. Am. Chem. Soc., 127, 13144 (2005)

 Fukuyama Group - Group Meeting Problems
01/18/2011
1 1) KH, THF, 20 °C;
trichloroethylene (1.1 eq) HO(CH2)2I
MeOH, –50 to 20 °C; N-Boc n-Bu3SnH HO(CH2)2
n-BuLi (2.2 eq), –70 to –40 °C pyrrole Et3B, dry air
i-PrSH BocN
2) MeCO3H neat, 85 °C CH2Cl2, 20 °C
MeOH-THF, 0 to 20 °C i-PrO2S
63%
53% (2 steps) 76%

D. M. Hodgson et al., J. Org. Chem., 70, 8866 (2005)

2 1) TTMSS, cat. AIBN H

CO2Me PhSe benzene, reflux O
OAc
quant. O
O
CH2Cl2 2) Pd(PPh3)4 (10 mol%)
O CO2Me
40 ºC PPh3, THF, rt
(16 kbar) quant. OAc

70%

I. E. Marko et al., Org. Biomol. Chem., 4, 1464 (2006)

3 t-BuPh2SiLi (1.0 eq.)

THF, –78 to 0 °C;
Cp2ZrCl2 reagent A
PhNC, –78 °C to rt (C33H34NSiZrCl)

71%
n-BuLi
THF-HMPA BnO
Me reagent A –78 °C;
CHO
Me
Me LiEt3BH, Et2O BnO(CH2)3I
0 °C to rt; –78 to 0 °C; Me
sat. NH4Cl aq 10% HCl aq.

73% 67%
M. Mori et al., Organometallics, 14, 1548 (1995)
M. Mori et al., J. Org. Chem., 61, 1196 (1996)
4
CO2Et 1) NH2OH·HCl 3) methyl propiolate
i-Pr CO2Et CO Me
NaHCO3 toluene, reflux H 2
i-Pr EtOH-H2O, rt, 76% 56%
O N
Bn N
N 2) AcOH, 100 °C
Bn
53% O H
O

V. Murray et al., Org. Lett., 6, 1931 (2004)

V. Murray et al., J. Org. Chem., 72, 3097 (2007)
 Fukuyama Group - Group Meeting Problems
01/26/2011
1
OAc AuClPPh3, AgSbF6
(3 mol%) O
Ph
OAc
CH2Cl2/H2O, rt Ph

82%

C. H. Oh et al., J. Org. Chem., 74, 370 (2009)

2
Bn
BnNH2, Ph3P MeO N CO2Me
MeO2C CO2Me
CH2Cl2, rt O
MeO CO2Me
71%

I. Yavari et al., Synlett., 15, 2293 (2010)

Pb(OAc)4 (2.4 eq) K2CO3 O

TMSO
C15H20O6
AcOH, 25 °C MeOH-H2O
TMSO 25 °C HO
75%
90%

S. Arseniyadis et al., Chem. Eur. J., 12, 7337 (2006)

4
IBX (2.0 eq.)
O O TsOH (0.2 eq.) IBX (3.0 eq.) IBX (2.2 eq.) O
O 5 O 5
PhF-DMSO DMSO THF-DMSO
HN 65 °C 90 °C N
85 °C
85% 76% 74%
Me Me

K. C. Nicolaou et al., Angew. Chem. Int. Ed., 40, 202 (2001)

K. C. Nicolaou et al., J. Am. Chem. Soc., 124, 2245 (2002)
 Fukuyama Group - Group Meeting Problems
03/05/2011
1 O
Ph
O · O Me
Me PPh3 Ph S
S
N Ph
Et2O, rt toluene
N3 rt to reflux
Ph
92% (2 steps)

M. Alajarin et al., Org. Lett., 11, 1365 (2009)

2 O

S ()
9

SH NaNO2 PPh2 S ()
HCl aq. (5 eq) 9

MeO MeO
NHAc MeOH CH3CN/PBS buffer NHAc
O rt rt to 50 °C O
73% (2 steps)

M. Xian et al., Org. Lett., 12, 5674 (2010)

3
O 1) H2O2, NaOH
MeOH OH
0 °C to rt PhSH (3 eq) OH
72% Cs2CO3 (5 eq)
SPh
CH2Cl2, rt HO
OH 2) O3, CH2Cl2
−78 °C; O
Me2S, rt 83%
PhS
95%

P. Wipf et al., Tetrahedron, 66, 5852 (2010)

4
[Ir(OH)(cod)]2 (5 mol%)
OH
P(n-Oct)3 (30 mol%)
Ph Me + OH
toluene
100 °C Ph

90%

Y. Ishii et al., Org. Lett., 11, 3510 (2009)

 Fukuyama Group - Group Meeting Problems
03/09/2011
1 CN CO2Et CO2Et
O O N
(2.0 eq.)
NHTol DBU (0.5 eq.) O O
HS
MeCN, 80 °C NHTol
Ar S S Ar
84% EtO2C N
Ar = p-ClC6H4

X. Xu et al., J. Am. Chem. Soc., 133, 1775 (2011)

2
TBSO
OC(O)Ar 1) NaH, toluene 3) DMP, CH2Cl2
PMBO CO2Et 110 °C, 85% rt CHO

TBSO CO2Et 2) LiAlH4, THF 4) CHCl3, reflux

92% (2 steps) O
0 °C to rt, 93%
Ar = 2,6-Me2Ph PMBO

R. K. Boeckman, Jr. et al., Org. Lett., 4, 3891 (2002)

3
n-BuMgCl (1.3 eq)
NiCl2 (1.0 mol%)
Br 1,3-butadiene (10 mol%) Br

Br THF, 0 °C n-Bu
quant.

N. Kambe et al., J. Am. Chem. Soc., 124, 4222 (2002)

4
O
1) CrO3, H2SO4
O DIBAL acetone, 0 °C O
tetracyclic
HN toluene compound
2) aq HCHO, pH 7.0 N
reflux 50% (2 steps)

71%
hexacyclic
compound

C. H. Heathcock et al., J. Am. Chem. Soc., 111, 1530 (1989)

 Fukuyama Group - Group Meeting Problems
03/19/2011
1
OTBS 1) pTsOH O
triphosgene [Pd(η3−allyl)Cl]2 CH3CN-H2O Ph
pyridine (5 mol%) rt, 93%

CH2Cl2, –78 °C (Me3Si)2, xylene 2) PhCHO O

100 °C BF3•OEt2 N
NHMe 58% CH2Cl2 Me
85% 0 °C to rt, 85%

Y. Takemoto et al., Org. Lett., 13, 1828 (2011)

2
CO2Et
EtO2C
Ph Ph3P EtO2C N
N
N3
MeO2C N N
MeO2C OH MeCN neat, 65 °C toluene, reflux
rt to reflux Ph
96% 57%
54%

F. Prati et al., Org. Lett., 9, 3461 (2007)

3
O

1) PhNCO, Et3N 1) 10% HCl aq. NBS O

MeO2C NO2 benzene, 50 ºC; THF, rt DMF, 0 ºC;
O
O 2) NH2OH•HCl Et3N, A MeO2C
N
A pyridine, rt 0 ºC to rt N O
O
96% (2 steps)
70-90%
89%

V. Stevens et al., Tetrahedron, 32, 1599 (1976)

4 Na (2 eq.*), EtOH
rt t 50 °C; 5M NaOH aq. H2O2•Urea
diethyl malonate A B
1,2-dibromoethane 50 °C MsOH
(1 eq.*) 22 °C 1H NMR (CDCl3):
86%
*theoretical amount 74% 77% δ 2.11 (s, 4H)

B (1.0 eq.*)
H2O (1.0 eq.*) OH
trans-stilbene 1M NaOH aq.
Ph + A
CHCl3 60 °C Ph
40 °C; OH
evap; 86%
syn:anti = 33:1

N. C. O. Tomkinson et al., J. Am. Chem. Soc., 132, 14409 (2010)

 Fukuyama Group - Group Meeting Problems
04/06/2011
1
O O
1) m-CPBA, K2CO3
N
O CH2Cl2, rt, 70% OH
N
Me 2) Zn powder
O O Me
THF/H2O, rt, 62%
H (β-/α-OH = >19:1) OH (β)

Y.-J. Li et al., Eur. J. Org. Chem. 1932 (2011)

2 O
O
Cr(CO)5 O
Cl
O
CH2Cl2 toluene
NMe4 –10 °C to rt 85 °C

53% (2 steps)

J. Barluenga et al., Org. Lett., 4, 2719 (2002)

3 O
O
1) BF3·OEt2 1) Et3N O
CH2Cl2, –20 °C formalin, rt H
O
2) H2, Pd/C 2) MeOH-6 M HCl aq.
O
O conc. HCl aq. rt N H
MeOH, rt 67% (2 steps)
N 94% (2 steps)
Bn H
L. E. Overman et al., J. Org. Chem., 58, 4662 (1993)

1) reagent A
K2CO3
4 1) SO2Cl2 (1 eq) CuSO4·5H2O
MeCN, rt; MeOH, rt
imidazole (2 eq), rt 75%
NaN3 (1 eq) reagent A L-Phe compoud B
2) AcCl, EtOH, rt 2) BnNH2
63% (2 steps) DCC, HOBt
DMF, rt
90%

Ph
O compound B O
AcHN AcHN
S PPh2 THF-H2O N CONHBn
rt H

80% E. D. Goddard-Borger et al., Org. Lett., 9, 3797 (2007)

R. T. Raines et al., J. Org. Chem., 67, 4993 (2002)
 Fukuyama Group - Group Meeting Problems
04/13/2011
1
OH CN
*DMSO, *(COCl)2 PhI(OAc)2 MeO2C
CH2Cl2, –78 ºC; NaBH4 I2, hν
N CO2Me N
Et3N MeOH CH2Cl2, rt I
NC –30 to 0 ºC O
62% 85%
90%
∗theoretically 2 eq.
S. F. Martin et al.,Tetrahedron Lett., 52, 2048 (2011)

2 1) NaH, MeI O
HO Ph3PAuCl (3 mol%) CeCl3 DMF, 45 °C
AgSbF6 (3 mol%) H2C=CHMgBr 80%
Me H H
Me
Me CH2Cl2, 23 °C THF, –78 °C 2) PdCl2(MeCN)2
DDQ Me
87% 72% THF, reflux
70%

F. D. Toste et al., Org. Lett., 10, 4315 (2008)

Me
AcO Me
PtCl2 (10 mol%)
O
O toluene, 100 °C
CO2Et OAc
H CO Et
2
72%

R. Sarpong et al., J. Am. Chem. Soc., 128, 6786 (2006)

4
H H
NO2 O H2 (1 atm) HO Ph
SMe2 Raney Ni H
Ph NH
CHCl3 EtOH H
CO2Et 0 ºC to rt 35 ºC OH
O O
H
89% 76% CO2Et

W. J. Xiao et al., Angew. Chem. Int. Ed., 48, 9542 (2009)

 Fukuyama Group - Group Meeting Problems
04/27/2011
1
diketene (2 eq), Et3N
COCH3 COCH3
HO THF, rt; Rh2(OAc)4 (cat.)
O O
OH MsN3 (2 eq), Et3N benzene, reflux
O O
77% 90%

A. Padwa et al., J. Org. Chem., 58, 21 (1993)

2
1) LDA (1.2 eq)
ClCO2Me (3.0 eq) 1) P2O5
PhI(OAc)2 (2.3 eq) Et2O, –78 °C CH3SO3H, rt
Ph KOH (3.0 eq) 79% 94%

O MeOH 2) KOH 2) PhI(OAc)2 (2.0 eq) I

–5 °C MeOH-H2O, rt I2 (1.5 eq), AIBN O
82% benzene, reflux
40% 92%

R. M. Moriarty et al., J. Med. Chem., 41, 468 (1998)

3
1) m-CPBA (1.2 eq)
Li, naphthalene CH2Cl2 1) m-CPBA (1.2 eq)
O DME –78 to –20 °C CH2Cl2 O
Br CHO
–50 to –20 °C; 70% –78 to –20 °C
O
HMPA, –55 °C; 2) TFAA, CH2Cl2 2) TFAA, CH2Cl2
PhSCH2I, DME 0 °C to rt; pyridine,
H H
–55 °C to rt NaHCO3 aq. 0 °C to rt;
94% NaHCO3 aq.
89% 47% (2 steps)

S. J. Danishefsky et al., J. Am. Chem. Soc., 133, 752 (2011)

4
OH

1) Ac2O, Et3N OMe

TBDPSO
DMAP 1) LiAlH4, AlCl3 MeO
Mn(acac)3 (1.6 eq) CH2Cl2, rt, 87% THF, rt
N
N MeOH, rt 2) TiCl4, TESH 2) (MeO)2CHCHO N OR
Ts H
N3 CH2Cl2, rt, 83% NaBH(OAc)3
88% AcOH
CH2Cl2, 0 °C R = TBDPS
43% (2 steps)

S. Chiba et al., J. Am. Chem. Soc., 133, 6411 (2011)

 Fukuyama Group - Group Meeting Problems
05/14/2011
1
BuO Et2Zn, LiI
cat. Ni(acac)2 HO2C
Pent NBS THF, 40 ºC; Jones' rgt.
C14H26O3
Me3Si OH CH2Cl2 O2, TMSCl, –5 ºC acetone, 0 ºC O
Pent O
88% 55% 90%

P. Knochel et al., Tetrahedron Lett., 36, 231(1995)

2 3) n-BuLi, CuI
1) I2, NaHCO3 TMSCl, THF
acetone-H2O, 0 °C –78 °C to rt n-Bu
87% 92%
BocHN O 2) MeI, Ag2O 4) vinyllithium Me N
CH2Cl2, rt THF, –78 °C Bn
99% 5) benzylamine (excess)
cat. p-TsOH
µW, 150 °C
42% (2 steps)

A. Padwa et al., Org. Lett., 11, 1233 (2009)

3
O Me O
o-dichlorobenzene N
O N
N
220 °C (MW)
H

60% 15%

C. D. Vanderwal et al., J. Am. Chem. Soc., 131, 7546 (2009)

[TpRu(PPh3)(CH3CN)2]PF6
(10 mol%)

toluene, 100 °C
I
86% I
Tp = tris(1-pyrazolyl)borate

R.-S.Liu et al., J. Am. Chem. Soc., 127, 4186 (2005)

 Fukuyama Group - Group Meeting Problems
05/18/2011

1 cyanoacetamide H
Ar
(3.0 eq.) CN
O CHO K2CO3
+
ethyleneglycol HN NH2
Cl H
mw, 120 °C
O N O
H
87%
Ar = p-ClC6H4

S.-J. Tu and G. Li et al., J. Am. Chem. Soc, 131, 11660 (2009)

2 Me
H
N
NH2•HCl
O Me PhI(OTf)2 OMe
K2CO3 MeOH
Me
H
MeOH CH2Cl2
–78 °C Me
rt
64% (2 steps)
6:1 dr
R. J. Thomson et al., Angew. Chem. Int. Ed., 50, 4437 (2011)

3
OH
NaOH SOCl2
CHCl3 toluene; O Me
Me
acetone Ph3P CN 260-270 °C
rt to reflux 1-2 Torr Me
Me Et3N CN
42% toluene, rt 54%
94%

J. M. Rao et al., Tetrahedron, 43, 5335 (1987)

E. J. Corey et al., J. Am. Chem. Soc., 91, 4782 (1969)
4

i-Pr LDA i-Pr

THF, –80 °C;
Ph N N
ZnBr2 Ph
NC
71%
(dr = 95 : 5)

F. Chemla et al., Chem. Eur. J., 16, 12668 (2010)

 Fukuyama Group - Group Meeting Problems
06/08/2011

1 O
toluene
(0.01 M)
N
reflux, 66 h O
N
96%

R. L. Danheiser et al., J. Am. Chem. Soc., 132, 13203 (2010)

2 1) NBS, Me2S 1) Et3OBF4

CH2Cl2, 0 °C to rt 3) K2CO3 CH2Cl2, reflux; O
70% DMF, 90 °C Red-Al, –78 °C
CH2OH C24H33NO2S
2) 50% (2 steps) 2) aq. Bu4NH2PO4
O
Ph
EtOH, reflux
N 54% (2 steps)
MeO S C17H23NO2S
LDA, THF, 0 °C;
then 1), 0 °C to rt A. I. Meyers et al., J. Am. Chem. Soc., 120, 5453 (1998)

3 Si
t-Bu

t-Bu benzaldehyde 1) MgCl

Ag3PO4 (10 mol%) Sc(OTf)3 (20 mol%) THF, –98 °C
70 °C; CSA (2 mol%) HO HO
92%
n-Bu OTBS n-Pr
toluene/CH2Cl2 2) TBAF Ph
CuI, 50 °C O
–78 to 22 °C THF n-Bu OH
n-Pr H 90%
89%
80%
K. A. Woerpel et al., Org. Lett., 8, 4109 (2006)
 Fukuyama Group - Group Meeting Problems
06/11/2011

1 1) ·
Br
n-Bu
CF3CO2Ag
OTIPS CH2Cl2
DMF Me
–78 °C to rt, 64% tetracyclic
O compound
2) hν (300 nm) 140 °C n-Bu O
MeCN/acetone (9:1) O
49% H
70%

H. Hiemstra et al., Eur. J. Org. Chem., 3146 (2011)

2
1) PhCHO,TiCl4 1) DBU
SiMe3 CH2Cl2, –78 °C THF, rt O
acyclic
O 87% compound 79% (2 steps)

2) MsCl, Et3N (except for Ph group) 2) HCl aq.

CH2Cl2, 0 °C EtOH, reflux Ph
73%

J. Matsuo et al., Org. Lett., 12, 3960 (2010)

3
C N CO2Et NO2 C N CO2Et
NH DBU DBU CO2Et
N N N
THF N THF H
EtO2C CO2Et PhO2S
rt R rt

91% 85%
(R=CO2Et) (R=SO2Ph)

G. W. Gribble et al., Chem. Commun., 1909 (1996)

G. W. Gribble et al., Chem. Commun., 1873 (1997)

4
Ph

N N
O N N Me
Me O
Me
N Br Ph
Me N
O N
toluene
Me N reflux Ph
Me Br
84%

Y. Cheng et al., J. Org. Chem., 76, 4746 (2011)

 Fukuyama Group - Group Meeting Problems
06/28/2011
1 NaH, PPh3
1) allyl glyoxylate DMF, –20 °C;
TBSO Me CO2Et toluene, reflux (PhO)2POCl TBSO
H H H H Me NHAlloc
(Dean-Stark), 89% DMAP, 0 °C;
S
Me CO2Et Me
2) SOCl2, pyridine NHAlloc S
NH O HS N
O THF, –60 °C O
3) i-Pr2NH, MeCN i-Pr2NEt, 0 °C OAllyl
0 °C, 86% (2 steps) O
66%

H. Horikawa et al., J. Org. Chem., 61, 7889 (1996)

2
POCl3, DMF MeI CN
CH2Cl2, rt; K2CO3 NaN3* N3
O C10H8ClNO
N H2O, 0 ºC acetone, rt DMSO, 97 ºC N
H Me
73% 97% 52%
∗theoretically 2 eq.

H. D. H. Showalter et al., J. Med. Chem., 40, 413 (1997)

J. Becher et al., J. Org. Chem., 57, 2127 (1992)
3

Me 1) LHMDS
Methyl methacrylate 3) K2CO3, MeOH Me
O hexane, –10 ºC to rt, 70% rt, 90%
Me O
C15H22O5
Me Me
Me 2) O3, CH2Cl2-MeOH 4) p-TsOH, benzene
–70 ºC; evaporation; reflux, 65% CO2Me
Ac2O, Et3N, DMAP
benzene, reflux, 61%

A. Srikrishna et al., Tetrahedron Lett., 47, 363 (2006)

O O Me2SO4 (1.1 eq.) NHMe

PhNHNH2 (1.0 eq.) xylene, reflux; evap.; toluene
OEt
Me
EtOH, reflux 50% aq H2SO4, 100 °C; reflux
O aq NaOH (neutralization) N Me
63% 79%
89%

A. Schmidt et al., Angew. Chem. Int. Ed., 49, 2790 (2010)

 Fukuyama Group - Group Meeting Problems
07/17/2011
1 [Fe2(CO)9]* (2 eq)
O HO BF4 benzene O O O
O
KOCEt3 (3 eq) 95 °C;
+ PhI
H
THF DBU (20 eq)
Me –78 °C to rt 95 °C

74% 51%
* low yield under basic condition

E. M. Carreira et al., Angew. Chem. Int. Ed., 50, 2962 (2011)

2
O
Dy(OTf)3
PhHN
O
CH3CN, 80 °C
OH
PhN
90%

J. R. Alaniz et al., Angew. Chem. Int. Ed., 50, 7167 (2011)

3
Ph3PEtBr Me CF3
Me TFAA (3 eq*) n-BuLi, THF
Ph N CO2H
AcOEt –20 °C to rt; Ph
O 0 °C to rt N
AcOH, 80 °C Me
87% 87%
(* theoretically 2 eq)

M. Kawase et al., Org. Lett., 12, 4776 (2010)

4
Boc
SiMe3 BocNHOH (2.5 eq) NH OH
NaIO4 (2.5 eq) OsO4, NMO SmI2 HO *1 OH
H
MeOH/ H2O THF/ t-BuOH/ H2O THF
20 °C 20 °C –78 °C HO NBoc
OH OH
52% 82% 60%
*1 stereochemistry
not determined

Y. Landais et al., Org. Lett., 10, 4195 (2008)

 Fukuyama Group - Group Meeting Problems
07/24/2011
1
1) MeMgBr, CuBr•Me2S
H H H O Me2S, THF, –20 ºC H O
MeO BHT, PhH 66%, 14:1 dr BHT, PhH
MeO
H H
235 ºC, 88% 2) TMSCHN2 120 ºC, 96%
H MeOH/PhH, rt, 93% CO2Me
O O
Me

M. L. Snapper et al., Org. Lett., 3, 2819 (2001)

O
2
O
O [Rh(OCOC7H15)2]2 (cat.)
N2 DMAD
MeO2C
CH2Cl2 H
N rt MeO2C
N
O 70%

A. Padwa et al., Tetrahedron Lett., 34, 7853 (1993)

3
1) CrO3
H2SO4/H2O/acetone
HO rt, 96%
2) OsO4, THF O
LTA rt, 79%
Tricyclic Compound O O O
(C17H24O3) 3) p-TsOH⋅H2O
CHCl3
-40 °C toluene, reflux
85%
61%
T. R. R. Pettus et al., J. Am. Chem. Soc., 133, 1603 (2011)

4
1) DDQ
MeCN-H2O (10:1) CAN
Ph Ph NIS (2.5 eq) MeCN-H2O (1:1)
60 °C O
H2O (5.0 eq) 58% (36% SM) rt; O
O O I
MeCN 2) NaH2PO4, NaClO2 K2CO3 O
–40 to 0 °C 2-methyl-2-butene
t-BuOH-H2O (5:1), rt 80%
62%* 92%
(*18% other diastereomixture)
Y. Kita et al., Angew. Chem. Int. Ed., 44, 734 (2005)
 Fukuyama Group - Group Meeting Problems
07/31/2011
1
N2 1) allyl alcohol 3) H(OH)NMe⋅HCl
O Rh2(OAc)4 pyridine, MeOH O
CH2Cl2, rt reflux MeN
O H
O 2) xylenes 4) imidazole⋅HCl
N reflux EtOH, reflux O
Me 85% (2 steps) 81% (2 steps) N
Me

J. L. Wood et al., Tetrahedron, 66, 6647 (2010)

2
OH

NMe
O
OAc
NMe
* TFA, rt N
OH H
N
H 61%
* : Diastereomixture
S. Blechert et al., J. Am. Chem. Soc., 126, 3534 (2004)

3
1) DMP O O
Pd(PPh3)4, i-Pr2NH CH2Cl2, rt O
O OH
microwave 77% O
O O
Br benzene 2) cat. RuCl3, NaIO4
MeO2C 160 °C CCl4-CH3CN-H2O
50% H CO2Me
60%

J. Suffert et al., Angew. Chem. Int. Ed., 50, 3285 (2011)

O
TBSO O 1) CsF, PhN(Tf)2
SmI2, HMPA DME LDA NMe
N
Me i-PrOH 2) Pd(OAc)2, PPh3 THF, –78 °C;
I THF, –35 °C MeI
HCO2H, DMF Me
87% (2 steps)
99% 67%

Y. Landais et al., Org. Lett., 10, 4441 (2008)

 Fukuyama Group - Group Meeting Problems
09/07/2011
1
ethyl diazoacetate 1) O3, CH2Cl2, –78 ºC;
Cu(OTf)2 (2 mol%) Me2S, 94% Me Me
Ligand A (2.5 mol%) 2) BF3•OEt2, –78 C; O
PhNHNH2 (2 mol%) allyltrimethylsilane O O
O
N N
O CO2Me CH2Cl2 3) Otera's cat. (0.05 mol%) tBu
tBu
1,2-ethyleneglycol O O A
53%, >99% ee benzene, reflux
(after recrystallization) 72% (2 steps,
anti/syn= 95:5)
O. Reiser et al., Org. Lett., 3, 1315 (2001)

2 1) methyl acrylate 1) LiAlH4, THF

Tf2O, pyridine BF3·OEt2 0 °C to reflux Bn
O CH2Cl2, –78 °C to rt; toluene, 50 °C 95% n-Pr N
OMe C25H29NO3 3 OBn
Ph N BnO(CH2)3MgBr 2) AlCl3, LiAlH4 2) Tf2O
H –10 °C Et2O-CH2Cl2, rt; CH2Cl2, rt;
BzCl, aq. NaOH Et3N;
Et2O, rt n-PrMgBr
37% (3 steps) 90%, 95% ee

A. B. Charette et al., J. Org. Chem., 75, 7465 (2010)

3
1) PtCl2 (5 mol%)
toluene, 80 °C
O 95%

2) p-TsOH (10 mol%)

benzene, reflux O
91%

C. H. Oh et al., Chem. Eur. J., 15, 71 (2009)

4 n-BuLi, THF, –78 °C;

MgCl
O OMe
OMe Mg, LiCl 1) DBU, THF O
THF, rt; –78 °C to rt; reflux, 95% Me
OMe
CO2, –78 °C to 0 °C; 2) Rh2(cap)4 H
Br OMe I2, 0 °C to rt (10 mol%)
t-BuOOH, K2CO3
N
56% CH2Cl2, rt, 77% O
F BF4
CH3OC4H9 cap: caprolactam
0 °C
M. Beller et al., Angew. Chem.Int. Ed., 49, 2219 (2010)
48% Anthony G. M. Barrett et al., Org. Lett., 10, 3833 (2008)
 Fukuyama Group - Group Meeting Problems
09/14/2011
1 Et
1) AlCl3 3) PhNHOH
OAc 120 °C benzene, rt CO2Et
95% 75% N
C10H6O3
2) (COCl)2 (5 eq) 4) Et H
DMF, rt CO2Et
86% H O
benzene, reflux
60% HO

B. C. Raju et al., Bioorg. Med. Chem. Lett., 21, 2855 (2011)

M. P. S. Ishar et al., Tetrahedron, 65, 4593 (2009)

2 O OMe hυ
benzene, rt;
O
TMSOTf
Et3N, rt

72%
K. Mikami et al., Synlett, 469 (1998)

3
O
Cl OBn
1) A BnO
N S O
O Py, CHCl3, rt BnO
OBn 43%
O BnO
O A O Me O
CH2Cl2, rt BnO
2) Ra-Ni
Me O benzene-toleune O
46% 0 °C to rt
45% O

R. W. Franck et al., Angew. Chem. Int. Ed., 35, 777 (1996)

4
Br CO2Et NaN3 (3 eq.) 1H NMR:
compound A* 4.48 (2H, q, J = 7.2 Hz)
DMF, 60 °C CH2Cl2 1.96 (2H, s)
Br 1.42 (3H, t, J = 7.2 Hz)
150°C (sealed tube)
71% *: not isolated

compound A 1) allyl bromide

OTMS CH2Cl2 K2CO3, DMSO
80 °C (sealed tube); 70% O
CO2Et
silica gel, rt 2) mCPBA, NaHCO3 N
OMe CH2Cl2-H2O, rt
86% 75%

K. Kondo et al., Chem. Lett., 525 (1982)

W. J. Chain et al., Tetrahedron Lett., 52, 939 (2011)
 Fukuyama Group - Group Meeting Problems
10/01/2011
1
n-BuLi (2 eq), –20 °C;
MeO2C Cl
O MeLi (1 eq) 1) NaH, THF, rt
THF, –80 to 40 °C; THF, –80 °C; 90% O O Me
Ph S Me
NMe 5% NaOH aq, rt O 2) Al/Hg
Me THF/H2O
86% –80 to –24 °C 58%
83%

J. Rodriguez et al., Synthesis, 2085 (2011)

2
O PPh3
1) Ac2O, pyridine O
TrocCl O O
O CH2Cl2, rt N
KHCO3 DIBAL 85%
N O
O
CHCl3, rt toluene toluene 2) Zn, NaH2PO4
–78 °C AcO
reflux THF-H2O, rt
OHC 91% 52% O
68% 55%

W. Z. Li et al., Org. Lett., 13, 3538 (2011)

3
i-BuCHO NH2
(1 eq) (1 eq) O2N Me
NH4Cl
toluene-H2O
OH 110 °C; N
Cl I TFA (0.2 eq); Cl
N O Cl
C Pd(OAc)2 (0.15 eq) i-Bu
Cl PPh3 (0.3 eq) HN
Et3N, 110 °C
NO2
(1 eq) (1 eq) 74%

L. E. Kaim et al., Org. Lett., 10, 3417 (2008)

4
AcO2H (1 eq.)
OBn CH2Cl2, –78 to 0 °C;
OBn
N
Ac2O, pyridine, rt N
Ac
TMS

S. Inoue et al., Chem. Lett., 37, 442 (2008)

 Fukuyama Group - Group Meeting Problems
10/08/2011
1
HO TsOH
MeO2C THF, 70 °C; RfSO2F, DBU

THPO LiAlH4, 40 °C; THF, 0 °C

O wet Na2SO4 O
filtration; 57%
Rf = CF2CF2OCF2CF2H

W. S. Tian et al., J. Org. Chem., 76, 1495 (2011)

2
n-Bu n-Bu
1) toluene, reflux Me
98% Me
O Me
2) Me Li
O
Me Me OH
OTMS H
THF, –78 °C to rt;
TBAF
45%

H. W. Moore et al., J. Org. Chem., 65, 8564 (2000)

3 n-C5H11
1) acetone, TFAA, TFA, rt, 84%
n-C5H11 HN
2) hν, MeCN, 0 °C, 95%
Ot-Bu
O N 3) NaBH4, THF, –78 °C, 65%
H O
O O 4) NaH, THF, rt, 95%
O
O

J. D. Winkler et al., J. Am. Chem. Soc., 111, 4852 (1989)

 Fukuyama Group - Group Meeting Problems
11/02/2011
1
1) DIBAL (1.1 eq.)
THF, –78 ºC; 1) mCPBA, CH2Cl2 OHC
H
A, –78 ºC, 79% 0 ºC to rt, 88%
tricyclic
compound O
O 2) TPAP (5 mol%) Ph2O 2) 70% HClO4
NMO, 4Å MS THF-H2O, 0 ºC O
O reflux H
CH2Cl2, 0 ºC to rt
68% 75%
MgBr
TMS
K. Inomata et al., Org. Lett., 6, 409 (2004)
A

2
Ph Pd(OAc)2 (5 mol%) MeO2C
MeO2C Ph
PhI(OAc)2 (1.1 eq.)
H
AcOH, 60 °C O

O O O O
79%

M. S. Sanford et al., J. Am. Chem. Soc., 129, 5836 (2007)

OAc
Ac2O H CO2Me
MeO2C OMe PhI(OAc)2 hν BF3•OEt2
+
OH MeOH, reflux acetone CH2Cl2, 60 °C OAc
H H
87% 68% 70% O

C.-C. Liao et al., Chem. Eur. J., 16, 3121 (2010)

4 EtO2C
CO2Et
HN MeI, rt;
hν evaporation; TFA
NMe
EtOH NaBH4 CH2Cl2, rt
N MeOH, rt N
Boc 82% 62% H
71%

J. D. White et al., J. Org. Chem., 75, 3569 (2010)

 Fukuyama Group - Group Meeting Problems
11/16/2011
1
Me O
Br 1) t-BuOK (2.0 eq), DMSO 1) mCPBA (1.5 eq), NaHCO3
30 to 40 °C, 85% CH2Cl2, 0 °C, 85% Br
OH 2) HBr aq, THF 2) ZnBr2 (4.7 eq), benzene Me
Me Ph 0 °C, 85% reflux, 80%
Ph

W-D. Z. Li et al., Ord. Lett., 7, 3107 (2005)

2
PPh3 (2.4 eq)
DBU (2.5 eq) BzCl (1 eq)
O N N
CCl4(2.5 eq) CH2Cl2, rt;
Ph
H N NH2 O Ph
MeCN PhCO2H
H 50 °C O
Et3N, rt

67% 54%

M. M. Bio et al., Synthesis, 19 (2005)

H. Yu et al., Tetrahedron Lett., 52, 5530 (2011)

3
SO2Cl

OH 1) TFA NO2
H
OH CH2Cl2, 40 °C, 75% NaHCO3 AcO
O
2) PhI(OAc)2 THF-H2O, rt
HO
CH2Cl2-HFIP, –17 °C;
HO
H2O2 aq 72%
64%
S. Canesi et al., J. Org. hem., 76, 9460 (2011)

4
Pd2(dba)3
NH2OH•HCl (2.5 mol%)
O O (3 eq) P(4-CF3C6H4)3 Me O
NaOAc (1 eq) (10 mol%) AcCl (1.2 eq)
Ph OEt N Cl
Ph
Me EtOH/H2O dioxane CH2Cl2 Me
reflux 80 °C rt
Me
59% 87% 91%

K. Ohe et al., Angew. Chem. Int. Ed., 50, 11470 (2011)

 Fukuyama Group - Group Meeting Problems
11/22/2011
1
3) disiamylborane, THF;
H2O2, NaOH
1) NaNO2, HCl 4) TsCl, DMAP, Et3N
NH2 O CuCl (20 mol%); CH2Cl2, 0 ºC to rt
MeOH, rt, 61% 64% (2 steps)
N N
2) allyltrimethylsilane 5) DIBAL, toluene, –70 to –15 ºC
TBSO TiCl4, CH2Cl2 6) NaI, Et3N, toluene, reflux TBSO
–78 ºC to rt, 91% 59% (2 steps)

S. M. Weinreb et al., J. Org. Chem., 65, 6293 (2000)

2
O
Me N N 1) DIBAL, CH2Cl2 Me
TsCl, –78 to 0 °C KHMDS (3 eq)
HO O O Me
O K2CO3, i-Pr2NEt 99% THF, –78 °C; Me

CH2Cl2, rt 2) TsCl, LiBr MeI

pyridine, 60 °C; –78 °C to rt
Me 83%, dr > 19:1 (EtCO)2O, Et3N
DMAP, rt 84% Me
79%

D. Romo et al., Angew. Chem. Int. Ed., 50, 7537 (2011)

3
n-Hex Br Cp2TiCl2 (12 mol%) n-Hex SiPhMe2
MgCl
THF-Hexane
(3 eq) –20 °C;
PhMe2SiCl
–20 °C to rt

72%
(E/Z = 97/3)

N. Kambe et al., Chem. Commun., 5836 (2008)

4 +
1) cat (2 mol%) SbF6−
CH2Cl2, rt O t-Bu
99% P t-Bu
O Au
2) SiO2
O NCMe
O CH2Cl2
70 °C, 100%
cat

L. Fensterbank et al., Angew. Chem. Int. Ed., 50, 6868 (2011)

 Fukuyama Group - Group Meeting Problems
11/26/2011

1 n-BuNH2
OH MeOH-EtOH 1) Ac2O, Py OH
50 °C; 0 °C to rt, 94% NaOMe
HO O O Me
HO OH SiMe3 MeOH, rt OH
CS2, 50 °C 2) OH
OH HO
73% OTf 99%
CsF, MeCN, rt
64%

J. R. Hwu et al., Chem. Eur. J., 17, 4727 (2011)

2
Ti(Oi-Pr)4
i-PrMgCl
Br
Me CO2Et
Et2O, –78 to –50 °C;
A; –50 to rt Me Me
A
CO2Et
73%

F. Sato et al., J. Am. Chem. Soc., 124, 9682 (2002)

3
O O O
AcO
NaBH4
CaCl2 Ac2O
O
O TMSOTf
Et3N MeOH
0 °C –20 °C O OAc
OAc MeCN
0 °C to rt OAc
93% 50%
70%

J. L. Mascareñas et al., Org. Lett., 4, 3091 (2002)

CF2 1) TBAF 1) TBAF (0.3 eq) Ph

THF, 0 °C THF, rt, 84%
Me Me Me
Ph
2) MsCl, Et3N 2) MeMgBr
OTBS CH2Cl2, rt cat. CuI, THF O
86% (2 steps) –78 to –40 °C
78%
T. Yamazaki et al., Org. Lett., 3, 743 (2001)
 Fukuyama Group - Group Meeting Problems (Nagoya)
05/23/2012

1
SOCl2 (2 eq) S
H2N NH2 N N
NEt3 (4 eq)

CH2Cl2, reflux

D. H. Lee et al., Dyes and Pigments, 91, 192 (2011)

2 O
Cl

OMe OH O
OMe O O
NaH (2 eq)
O
THF, 0 °C to rt MeO
MeO O
O

D. Trauner et al., Angew. Chem. Int. Ed., 50, 1402 (2011)

3
1) Bu3SnH (1.2 eq)
AIBN (cat) OH Me
O Br benzene, 80 °C

Me3Si 2) TBAF, THF

H

Y.-M. Tsai et al., Tetrahedron Lett., 34, 1303 (1993)

 Fukuyama Group - Group Meeting Problems (Nagoya)
05/30/2012

1
O O
Br H
Me H DMDO Me O H
Me NaHCO3 Me
OHC OHC
O Me O Me
acetone, rt
O
N N
Me Me

V. H. Rawal et al., J. Am. Chem.Soc., 133, 5798 (2011)

2
LHMDS (2.4 eq) Me
Me TBHP (1.1 eq) HNTf2 (1.2 eq) Me
THF, –78 °C to rt; CH2Cl2, rt;

TIPSOTf (1.1 eq) C5H11 aq NaHCO3

C5H11 THF, –78 °C to rt C5H11 O
OTIPS

J. P. Morken et al., J. Am. Chem. Soc., ASAP (2012)

3
O
O AgBF4 (0.2 eq)
HN DIPEA (1.5 eq);
O N
+ Ph +
N N O
H wet NMP, 75 °C Ph
H N
H H

J. Zing et al., Chem. Commun., 47, 12855 (2011)

 Fukuyama Group - Group Meeting Problems (Nagoya)
06/06/2012
O
1 Ph
S
H H Ph
OH NaH (1.5 eq) O S
KH (cat)
O
H THF, rt H
H 98% H
H OTBDPS H OTBDPS
OMOM OMOM
MOMO MOMO
H
H
MOMO H
NaHCO3 (40 eq)
MOMO
1,2-dichlorobenzene
170 ºC OHC
89% OTBDPS

H. Takayama et al., Angew. Chem. Int. Ed., 50, 8025 (2011)

2
A (10 mol%) A:
CuI (5 mol%)
CH2=CH2 (1 atm) N N
toluene, 80 °C; Ph CO2H
Ph Ph Cl
Ru
B (5 eq) Ph CO2H Cl
100 ºC; PCy3 Ph
DDQ (1.2 eq)
88% B:
HO2C CO2H

C. Feng et al., Chem. Commun., 48, 356 (2012)

3 MeI, t-BuOK TIPSO 1) Comins reagent TIPSO

MeO OTIPS THF KHMDS, THF
O O
–78 °C to rt; MeO –78 °C to rt MeO
O Me
2 N aq HCl Me Me 2) CO, Pd(OAc)2 Me
THF, rt DPPF
MeO 58% MeO2C
O Et3N, DMF
MeOH, 50 °C
81% (2 steps)

Cl

Tf
N N
Tf
Comins reagent

M. Nakada et al., J. Org. Chem., 77, 5098 (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
06/13/2012

1
N2 H O
NH2 microwaves (300 W) N
O O Tmax = 180 ºC, 6 min
+
NH2 touene (0.2 M) N

(1 eq) (1.0 eq)

J. C. Castillo et al., Eur. J. Org. Chem., 2338 (2012)

tBuO2C CO2Et O
N +
O CO2tBu
toluene, 80 ºC
CO2Et 79% CO2Et

(1 eq) (3.0 eq) N CO2Et

J. Yang et al., Angew. Chem., 124, 5200 (2012)

Bn Me
N
Cl S Me
O (0.1 eq) OH O
O
AcO AcO
H i-Pr2NEt (0.08 eq) OEt
EtOH
83%, 5:1 dr 5:1

D. A. Vosburg et al., Org. Lett., 11, 2217 (2009)

 Fukuyama Group - Group Meeting Problems (Nagoya)
06/20/2012

1
OMe OMe OMe OMe
LiCl (10.0 eq)
LDA (2.3 eq)
THF, –78 ºC Ph
S Nt-Bu
then A Cl
N –78 ºC N
H O 67% H OH A (1.9 eq)

D. Trauner et al., J. Am. Chem. Soc., 134, 9291 (2012)

2
N3

O
TMSO TiCl4 N
OMe
CH2Cl2
–78 to 10 °C H

MeO OMe 82%

(dr = 1:0.84)
Y.-Q. Tu et al., Org. Lett., 13, 724 (2011)

3
O O
PPh3 (1.36 eq)
O THF, rt;
N N3 N N
H2O, rt, 6 h

CO2Me 75% (dr = 5.8:1) CO2Me

M.-X. Zhao et al., Eur. J. Org. Chem., Early View (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
07/03/2012

1
Ph
N
Ph Ph
N N DMAD (10 eq) N N CO2Me
N N
THF
60 °C, 62% CO2Me
Ph

M. Bancerz et al., Tetrahedron Lett., 53, 4026 (2012)

AcO
PtCl2 (2 mol%)

toluene, 80 °C
AcO H
H
92%

A. Fürstner et al., Chem. Eur. J., 12, 3006 (2006)

3
O 1) DIBAL-H O
H toluene
O O –78 ºC H O
HO O
2) O2, hv OH
Rose Bengal
CH2Cl2
–78 ºC

I I
O O O–

I I
Cl COO–

Cl Cl
Cl
Rose Bengal

D. T. Hog et al., Nat. Prod. Rep., 29, 752 (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
07/11/2012

1
TBSO O 1) H2, Raney-Ni (excess) H
AcOEt, rt, 88% OTBS
n-C6H13
N3
O 2) NaBH(OAc)3 (4.0 eq) N
OAc CH2Cl2-AcOH (50:1)
82% AcO n-C6H13

P. Renaud et al., Org. Lett., 13, 4774 (2011)

2
Et Et
O
AgOTf O
I N Me3P N
Et3N H
C20H22N2O3
toluene benzene H
0 °C to rt MeOH
N CO2Me N CO2Me
H 80% H
C20H23IN2O3 (2 steps) C20H22N2O3

O. Kwon et al., Chem. Sci., 3, 2510 (2012)

3
O IPrAuCl / AgNTf2 OBz
OBz N
5 mol%
+ NHPh
DCE N O
25 °C to rt Ph
(2.2 eq)
74%
V. V. Pagar et al., J. Am. Chem. Soc., 133, 20728 (2011)
 Fukuyama Group - Group Meeting Problems (Nagoya)
07/18/2012

1
O BF3·OEt2 (1.5 eq)

CH2Cl2, –40 °C

87%

H.-G. Schmalz et al., Synlett, 2487 (2011)

2
O 1) LHMDS (2.6 eq)
O TBSCl (3.0 eq) H H
t-Bu Si HMPA, THF O
O O CO2TBS
t-Bu t-Bu Si
O 2) benzene
80 ºC O
t-Bu H
O
85%

C.-L. Chen et al., Org. Lett., 11, 409 (2009)

1) methyl propiolate
NOH MeOH, reflux N
MeO2C N Ph
H2N Ph 2) Ph2O, reflux H

N. D. Heindel et al., Tetrahedron Lett., 12, 1439 (1971)

 Fukuyama Group - Group Meeting Problems (Nagoya)
07/24/2012

250 ºC O
O OTBS
toluene
OTBS
87%
S. Kobayashi et al., Synlett, 1427 (2012)

1) CH2N2, Et3N
Et2O, 60% O
O O
OTIPS 2) Cu(acac)2 OTIPS
Cl O
THF, reflux
91%

A. J. Phillips et al., Angew. Chem. Int. Ed., 48, 2346 (2009)

3
1) NaH, Tf2O H
CH2Cl2 H
HO
N3 N +
2) DIBALH
68% N
trans:cis = 1:1
1:1

A. Kapat et al., J. Am. Chem. Soc., 131, 17746 (2009)

 Fukuyama Group - Group Meeting Problems (Nagoya)
07/31/2012

1
O LDA (4.0 eq) O OMe
methyl acetate (4.0 eq)
O
THF O
O OH
tBu 77%

H. Burghart-Stoll et al., Eur. J. Org. Chem., 3978 (2012)

2
s-BuLi (2.2 eq)
THF, –78 °C;
O Me
A, –78 to –60 °C; Me Me
O S
Br Me
NH s-BuLi (1.2 eq) Br Me
N A
–78 to 0 °C;
BrCH2CH2Br
Me Me –78 to 0 °C

70%

Y. Hayashi et al., Angew. Chem. Int. Ed., 45, 789 (2006)

3
NPhth OMe O
NH
N H
Sc(OTf)3 (2.0 eq) O
OH
N DMF, 150 ºC
H
37% N N OMe
HN H H H
O NPhth

U. K. Tambar et al., J. Am. Chem. Soc., 133, 10050 (2011)

 Fukuyama Group - Group Meeting Problems (Nagoya)
08/08/2012

1
NH2
HOAc N
COOCH3 +
EtO OEt reflux COOCH3
O
80%

A. D. Josey et al., J. Org. Chem., 27, 2466 (1962)

2
O
benzyl bromide (1.1 eq)
O NaN3 (1.2 eq)
CuSO4•5H2O
N
N O O
DMSO
O O N
81%

Y. Zhang et al., Eur. J. Med. Chem., 53, 365 (2012)

3
OMe LiTMP (7.6 eq) OMe
CH2(CO2Me)2 (3.8 eq)
O O CO2Me
THF, –78 °C
CO2Me
Br
45%
A

A solution of the substrate A in THF was added to a mixture

of LiTMP and dimethyl malonate in THF at –78 °C.

Y. Kita et al., Angew. Chem. Int. Ed., 46, 7458 (2007)

 Fukuyama Group - Group Meeting Problems (Nagoya)
08/22/2012

1
O
NC
CN
NH2
O
piperidine (1.0 eq)
O
N O
EtOH, rt
N3 N
67%

P. T. Perumal et al., Synlett, 1950 (2012)

H O OTIPS
OHC O
HO2C N H
Br N
MeOH-THF N
O H
O
rt O
H2N CN O
OTIPS 67%
HN
Br
OTIPS

1) KHMDS (>2 eq)

O allyl bromide (>2 eq)
H THF, rt, 89%
N
N O
2) Grubbs catalyst
H O (2nd generation)
O CH2Cl2, 40 °C
H H N 69%
Br

S. L. Schreiber et al., Org. Lett., 2, 709 (2000)

 Fukuyama Group - Group Meeting Problems (Nagoya)
08/29/2012

1
acetaldehyde
[{Pd(allyl)Cl}2] (0.1 eq)
PPh3 (0.3 eq)
OH OBoc KHMDS (1.5 eq)
O O
TBDPSO toluene
TBDPSO
–78 ºC to rt

91% (d.r. 9:1)

D. Menche et al., Angew. Chem. Int . Ed., 51, 9425 (2012)

2
O
O Bu3SnH (1.25 eq)
AIBN (0.12 eq)
CO2Me
toluene
I reflux CO2Me
72%, dr = 1.1:1

C.-K. Sha et al., Tetrahedron Lett., 41, 9865 (2000)

3
OH HO HO
O OH
mCPBA (1.3 eq) H H
O +
CH2Cl2 O O O
OH OH
0 ºC
A B
67%
(A:B = 10:1)

Z. Yhang et al., J. Org. Chem., 74, 9546 (2009)

 Fukuyama Group - Group Meeting Problems (Nagoya)
09/12/2012

1
O O
Ph CAN (2.0 eq)
+
MeOH
O 5 ºC O Ph
99%
N. Vijay et al., Tetrahedoron, 65, 10745 (2009)

2
TBSO OTBS
TBSO OTBS
n-BuLi (4 eq) TMS
OBn
O O OBn
THF O
–78 °C HO
H TBDPS
TMS TBDPS 54%
dr = 84:16

K. Tomooka et al., Angew. Chem. Int. Ed., 39, 4502 (2000)

CHO NH2
OH HO
A, MS 3Å MeO
+ +
CH2Cl2
25 °C N
NO2 OMe H
86% NO2
dr = 14:1

Cl

O O
P
O OH

Cl
A

L.-Z. Gomg et al., J. Org. Chem., 77, 6970 (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
09/26/2012

1
1) PhI(OAc)2 (1.05 eq)
CHCl3;
OH MgO (2.3 eq) F
OH Deoxofluor (6.0 eq) OH

2) NaBH4 (5.0 eq)

DBU (5.0 eq)
EtOH
0 °C
S. Akai et al., Org. Lett., 13, 2714 (2011)

OH 1) MeLi, Et2O-THF OAc

H –78 °C H Me
DMDO 42% (2steps)
ketone
O O
acetone-CH2Cl2 C23H34O5
2) Ac2O, DMAP
H –78 °C CH2Cl2, 0 °C H OH
OPiv 73% OPiv
C23H34O4

S. J. Danishefsky et al., Angew. Chem. Int. Ed., 37, 185 (1998)

3
1) NaOAc (2.0 eq) Me Me
Me NH2OH•HCl
O EtOH, reflux
Me 2) H2SO4, reflux NC NC
Me 83% (mixture) Me Me
Me Me

2:1

L. E. Overman et al., Angew. Chem. Int. Ed., 51, 9576 (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
10/03/2012

OH
nBu3SnH (2.0 eq)
AIBN (0.5 eq) OH
benzene H
O reflux, 72% O
SnnBu3

S. J. Gharpure et al., Tetrahedron Lett., 50, 7162 (2009)

2
Ph3SnH (1.5 eq) O CF3
CF3 CF3 AIBN (0.1 eq)

O O OCH3 benzene
reflux Ph3Sn
80%

CF3 OCH3
Ph3SnH (1.5 eq) O
CF3 H AIBN (0.1 eq)
O
O O OCH3 benzene
H
reflux
64% Ph3Sn

J. E. Wulff et al., J. Org. Chem., ASAP; doi: 10.1021/jo301565u

3
1) mCPBA (1.0 eq)
CH2Cl2
–20 ºC, 12 h O

2) 3-pentanone (1.05 eq) O

BF3•Et2O (0.1 eq)
0 ºC, 6 h
57%
C. R. Unelius et al., Org. Lett., 12, 5601 (2010)
 Fukuyama Group - Group Meeting Problems (Nagoya)
10/10/2012

1
CO2Et
O O
O HO H
CO2Et
O H2O
H
TFA H
O rt, 85% O

O O

G. Pattenden et al., Tetrahedron Lett., 50, 7310 (2009)

O
Ph O O toluene Ph Ph
+
N3 Ph Ph 100 °C
N Ph
1 eq 1.2 eq 95% H

S. Chiba et al., Tetrahedron, 67, 7728 (2011)

Bn CO2Me
H O N
BnNH2
N
CH2Cl2 Bn
CO2Me N
rt, 5 h
MeO2C Bn
quant

K. Tanaka et al., Tetrahedron Lett., 53, 5899 (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
10/17/2012

1
OMe O
mCPBA (2.0 eq)

CCl3CN-MeCN (1:1)
0 ºC to rt, 88%

M. Inoue et al., Org. Lett., 12, 4195 (2010)

2
O
BnO
H
(20 mol%)
H Ph NOH
Ph NHOH + N Ph H
benzene, rt N Ph

75%

A. M. Beauchemin et al., J. Am. Chem. Soc., 134, 16571 (2012)

O O
HO p-TSA (10 mol%) H
+
ClCH2CH2Cl, rt H
HO
O
69%

J. S. Yadav et al., J. Org. Chem., 75, 2081 (2010)

 Fukuyama Group - Group Meeting Problems (Nagoya)
10/24/2012

1
O
Pd/C (0.38 eq) O
H2 (1 atm) K2CO3 (1.2 eq)
CHO C15H20O3
MeOH-EtOAc (2:3) dioxane, 125 ºC O
rt, 61% 50%
HO

Chemical Formula: C15H16O3

K. C. Nicolaou et al., J. Am. Chem. Soc., 131, 10587 (2009)

2
SbBrCl5
Br O
BocO
S
Et Et O O
Me (BDSB)
O
MeNO2
–25 to 25 °C Br Me
O
Me
67% Me

S. A. Snyder et al., J. Am. Chem. Soc., 133, 15898 (2011)

3
O t-Bu
Cl
H t-Bu (2.0 mol%)
O O
BnO NH THF; NH
O n
BnO O LiHMDS (5.0 mol%)
H 0 ºC, 61% O OBn
OBn
OBn
OBn

M. W. Grinstaff et al., J. Am. Chem. Soc., 134, 16255 (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
10/31/2012

1
Tf2O (1.05 eq)

H O
O N (1.2 eq)
TBDPSO TBDPSO
N
DCE, rt, 94%
H

L. Ghosez et al., Tetrahedron, 59, 6797 (2003)

2
SiMe3
Rh2(esp)2 (0.5 mol%)
O SiMe3
N2 O
CH2Cl2, 20 °C
O
78% O

Rh2(esp)2 = bis[rhodium(α,α,α',α'-tetramethyl-
1,3-benzenedipropionic acid)]

J. A. May et al., J. Am. Chem. Soc., 134, 17877 (2012)

3
O

PMP PMP (0.1 eq)

OH (COCl)2 (1 eq) Cl
CO2Me CO2Me
Ph PhCF3, 80 °C Ph

90%

T. H. Lambert et al., Angew. Chem. Int. Ed., 50, 12222 (2011)

 Fukuyama Group - Group Meeting Problems (Nagoya)
11/07/2012

1 CO2Me CO2Me
O
NH2 ninhydrin (1.0 eq) N
aq HCl, reflux, 24%
N N
H H HO

M. M. Joullie et al., Tetrahedron, 59, 6933 (2003)

2 OAc
OAc
AcO O
AcO AcO O
AcO
AcHN
O AcHN
lauroyl peroxide O
S S
EtOAc, reflux
Br OEt
Br S S 59%
OEt N O
N O
OAc
OAc
OAc
lauroyl peroxide
AcO O EtOAc, reflux
AcO
AcHN 79%
O
Br

HN
O S. Z. Zard et al., Org. Lett., 14, 5514 (2012)

3
18
OH O
NH H
+ HO N
O DMSO
40 ºC 18 O
1.0 eq 1.1 eq

J. W. Bode et al., Angew. Chem. Int. Ed., 51, 513 (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
11/13/2012

1 Et
Tf2O (1.1 eq) EtS
O H
Me3Si N CHCl3, rt; H O
TBAT (1.1 eq) Me N
65 ºC, 51%
OTf
O
EtS

D. Y. Gin et al., Angew. Chem. Int. Ed., 41, 1788 (2002)

2
O OH SmI2 (2 eq) Me
HMPA, t-BuOH
Me
H THF, 0 °C Me
OH OH
71%

J. D. Kilburn et al., Tetrahedron Lett., 43, 6201 (2002)

S
SnBu3
(2.0 eq) N
N N
N CuBr•Me2S (2.2 eq)
N N
Pd(PPh3)4 (0.05 eq) S
O + N
O S
N SCH3 N O S
THF, reflux N

12% 40%

D. Branowska et al., Tetrahedron Lett., 52, 7054 (2011)

 Fukuyama Group - Group Meeting Problems (Nagoya)
11/21/2012

Bu3SnH (1.5 eq) H

AIBN (5 mol%) O

toluene, 110 ºC
S Ph H
O 46%

P. Renaud et al., Angew. Chem. Int. Ed., 41, 4323 (2002)

2
Me
Me Me
O
Me
Me O
BF3·OEt2 (cat) Me
ClCH2CH2Cl
40 °C H

67%
F. G. West et al., Org. Lett., 5, 2747 (2003)

3
H
N

S X
PMP (2.0 eq) PMP
N A (10 mol%) HN
O O
toluene P
50 °C O OH
97% (92% ee) X X = 2,4,6-(i-Pr)3C6H2

T. Akiyama et al., Org. Lett., 11, 4180 (2009)

 Fukuyama Group - Group Meeting Problems (Nagoya)
11/28/2012

1
OMe
O O OMe O
TMSOTf (1.2 eq) H
O
MeO MeNO2, reflux
Me O MeO
Me
70%

E. Fillion et al., J. Am. Chem. Soc., 38, 13145 (2005)

2
Ph Ph

N N Li
N N
OBn
THF, 0 °C
N Ph
N 65%

S. Kim et al., J. Am. Chem. Soc., 121, 5330 (1999)

OAc
O NH2 Ph I OMe
O
OAc OMe
EtO EtO NH2
CN MeOH, rt
O Ph CN
O Ph
80%

M. Alla et al., J. Org. Chem., ASAP

DOI: 10.1021/jo301801b
 Fukuyama Group - Group Meeting Problems (Nagoya)
12/04/2012

1
CO2Et
CO2Et
I2 (2.5 eq)
N MeCN-H2O (10:1) N
rt
CHO
H
83%

I. Kim et al., Tetrahedron Lett., 48, 8976 (2007)

2
O
S O
Me Me I
O Me H
(3.8 eq) OMe
OMe
NaH (3.2 eq)
DMSO, rt O
O O H
O
73%

M. Yamashita et al., Org. Lett., 14, 6048 (2012)

Cl Cl H2N OH
OH
NEt3 (3.7 eq) N
OH
+
H2N CHCl3
O N
(1.0 eq) 45 ºC
Cl Cl Cl
90%

A. Guirado et al., Tetrahedron Lett., 48, 9173 (2007)

 Fukuyama Group - Group Meeting Problems (Nagoya)
12/12/2012

1
S N

O2N N O N
O NH DBU (2.2 eq)
+
Cl MeCN, 80 ºC
SH
81%

D. Zhang et al., Tetrahedron Lett., 48, 7476 (2007)

2
Cl
TBSO Cl H
AgBF4 (1 eq) MeO
Et
MeCN O
Et reflux H
Cl
OMe
81%

F. G. West et al., Org. Lett., 9, 3789 (2007)

3
O O Ph
OMe DBU (2 eq)
+ P Ph OMe
Br OMe P
MeCN, rt OMe
O O O O
(2 eq) (1 eq) 50% (trans:cis = 8:1)

DBU MeCN
(1 eq) rt

O Ph
Ph OMe
P
OMe
O O

A. S. Demir et al., J. Org. Chem., 73, 8992 (2008)

 Fukuyama Group - Group Meeting Problems (Nagoya)
12/25/2012

1
OMe
n-BuLi, Et2O Ph
OH (OC)5W
–78 ºC to –25 ºC;
O
1, Et2O, –25 ºC
Ph
OMe 1

J. Barluenga et al., Angew. Chem. Int. Ed., 44, 5875 (2005)

2
1) Ph3PAuCl (5 mol%) D
Me AgSbF6 (5 mol%) H
CH2Cl2, 10 °C
D Me Me
OMe 2) TsOH, acetone, rt
Me
OMe 91% O

R.-S. Liu et al., J. Am. Chem. Soc., 130, 16488 (2008)

3
O

O N
O O HO
O BF3•OEt2 (cat)
+ N +
H2N NH2 microwave N
H
80%
O
1 eq 1.6 eq 5.0 eq

R. C. Boruah et al., Tetrahedron Lett., 51, 5160 (2010)

 Fukuyama Group - Group Meeting Problems
1/17/2012

1 O
O
O
O 1) NiCl2·6H2O, NaBH4
H 1) FeSO4, I2 THF/MeOH (2:3)
1O H OH
2, *TPP MeOH, rt 0 °C to rt, 92%
O H
H CH2Cl2, hν 2) DBU, toluene 2) LAH, THF, 45 °C
0 °C 80 °C 66% OH
TBDPSO H
H
quant 69% (2 steps) TBDPSO
H
*TPP = tetraphenylporphyrin

W. Tian et al., Angew. Chem. Int. Ed., 50, 7093 (2011)

2 Me
Me
O Ph
O
CSA, H2O hν, Pyrex MeMgBr OMe
Bicyclic O
compound H
MeCN, rt MeCN, rt THF
MeO 0 °C to rt Me
MeO OMe 99%
52% Ph
82%

J. A. Porco Jr. et al., J. Org. Chem., 76, 9792 (2011)

J. A. Porco Jr. et al., Synthesis, 2254 (2010)
3
CO2Me
i-PrS
SO2Cl2
OH CH2Cl2, –40 °C; K2CO3 O O

Et3N acetone
–35 °C to rt reflux

77% 77%

K. Sato et al., J. Org. Chem., 52, 5495 (1987)

TESOTf
4 Ph3P
OMe CH2Cl2, 0 °C; OH

Ph OMe *PhMgBr (5.0 eq.) Ph Ph

dry air (containing O2)
0 °C

81%
*theoretically 3.0 eq.

H. Fujioka et al., Chem. Commun., 47, 9894 (2011)

 Fukuyama Group - Group Meeting Problems
2/15/2012

1 OMe
Me MeO
N
TfOH 1) TBHP, Triton B, THF, rt
MeO CH2Cl2, 0 ºC 2) SiO2, rt, 76% (2 steps)
MeN
MeO 97%
O HO
O

S. E. Reisman et al., Angew. Chem. Int. Ed., 50, 9447 (2011)

2
D Et3Si
Et3Si t-BuLi (3.0 eq.)*
D
SiEt3 O THF-HMPA SiEt3 OH
–78 °C
E:Z = 1:1
80%
* theoretically 1 eq.

Z. Song et al., Org. Lett., 14, 1094 (2012)

3
K, NH3 1) 6 N HCl
OMe t-BuOH (1 eq) MeOH, rt
O THF, –78 °C; 95% LiOMe Me
O
N piperylene; 2) I2, THF-H2O THF, –78 °C O CO2Me
MeI rt, 90%
OMe 87%
95%

S.-K. Khim et al., J. Org. Chem., 69, 7728 (2004)

4 Me Me
1) Rh(acac)(CO)2
(1 mol%)
CO (1000 psi) OH O OH
OH Me Si benzene, 60 °C
H H
i-Pr i-Pr
NaH (20 mol%) 2) H2O2, KF
Me hexane, reflux THF-MeOH, 40 °C Me Me Me
62% (2 steps)
87% d.r. = 15:1

J. L. Leighton et al., Org. Lett., 10, 5593 (2008)

 Fukuyama Group - Group Meeting Problems
04/04/2012

1
N3
( )3
TMSO O
TiCl4 1) AlCl3, EtSH, rt N
O
CH2Cl2, –78 to 10 °C 2) DMP
CH2Cl2, 0 °C to rt H
82%, dr=1:0.84 87%(2 steps)
MeO OMe

S. Zhang et al., Org. Lett., 13, 724 (2011)

2
Bu3SnH
O NIS AIBN H
DBU t-BuOH/benzene O O
Ot-Bu
CH2Cl2 reflux;
OH –40 °C to rt NIS, CH2Cl2 H
–20 °C I
73%
60%

P. Renaud et al., Angew. Chem. Int. Ed., 41, 4321 (2002)

3
1) mCPBA (1.0 eq) O
MgBr H H
CH2Cl2, 0 °C PCC BuSSBu

2) NaOMe THF, rt to 60 °C CH2Cl2, rt benzene, hν

MeOH, reflux H H
70% 66%
(isomerization) 81%

72% (2 steps)
M. E. Jung et al., J. Org. Chem., 62, 4601 (1997)

4
Pd(OAc)2 (5 mol%)
dppm (5 mol%)
I CsO2CCMe3 (2 eq.)

N DMF, 100 °C Ph
N
65%
Ph

R. C. Larock et al., J. Am. Chem. Soc., 125, 11506 (2003)

 Fukuyama Group - Group Meeting Problems
04/14/2012

1
S
Ph Ph3PAuCl (5 mol%)
S O AgSbF6 (5 mol%)

CH2Cl2, rt O
56%

F. D. Toste et al., J. Am. Chem. Soc., 129, 4160 (2007)

2
5 mol%
Me Grubbs 1st O
O Li H
Et3N Me generation cat.
Br Br
TFE/Et2O THF, –78 °C ethylene
–78 °C to rt CH2Cl2, rt H
90%
70% 50%

M. Harmata et al., Org. Lett., 7, 2563 (2005)

3
H O
Ph SeO2 HCO2H, t-BuNC O
N t-Bu N Ph
N
1,4-dioxane, reflux TFE, rt H
O
O O
72% 73%

X. Chen et al., J. Org. Chem., 77, 1386 (2012)

T. F. Molinski et al., J. Org. Chem., 61, 2044 (1996)

4
CN CO2Et MeO2C OEt
CHO CO2Me
MeOH, rt; O
+ +
toluene
NH2 reflux N
NO2
89%

J. Zhu et al., Eur. J. Org. Chem., 475 (2012)

 Fukuyama Group - Group Meeting Problems
04/16/2012

1 Ms
NHBoc TFA NH2
N O (C11H23COO)2 CH2Cl2, rt;
(10 mol%) (t-BuCOO)2 evap;
I
I S EtOAc PhCl Et3N
reflux reflux toluene, 90 °C N O
EtO S H
86% 73% 55%

S. Z. Zard et al., Org. Lett., 7, 1653 (2005)

S. Z. Zard et al., Org. Lett., ASAP (DOI: 10.1021/ol3005276)
2 Br NHBn
Br
O PhCH2NH2 OCHO
O K2CO3 NBS O
dichloroethane DMF, rt HCO2H, 80 °C
0 to 5 °C
O
92% 93%
89%
C.-H. Oh et al., Arch. Pharm. Chem., 340, 530 (2007)
F. Liang et al., Org. Lett., 14, 712 (2012)

3 i-Pr OTIPS
NaNH2 1) Br2, AlCl3, 80 °C hν (254 nm) HO OTIPS
OTMS bromobenzene 81% 1,2-dichloroethane;
Me Br
THF 2) trisyl azide, n-Bu4NBr reflux
45 °C to reflux 18-crown-6, KOH
benzene-H2O, rt 62%
42% 77% Me

R. L. Danheiser et al., J. Am. Chem. Soc., 116, 9471 (1994)

4 CO2Me
CO2Me
1) EtMgBr, Ti(Oi-Pr)4 (cat.) CO2Me , I MeO2C
Et2O, 20 °C, 99% Pd(OAc)2, Ph3P, Et3N
CO2Me
2) Ph3P, Br2, pyridine DMF, 75 °C
CH2Cl2, 20 °C, 78% MeO2C
3) t-BuOK, DMSO, 20 °C, 81% 49%
(diastereomeric mixture) CO2Me

A. de Meijere et al., J. Org. Chem., 58, 502 (1993)

A. de Meijere et al., Angew. Chem. Int. Ed., 34, 2545 (1995)

5 Cl N2
Me CO2Et
H CO2Et
NHBoc SCl
[Rh2((S)-tbsp)4]
(5 mol%) TFA Cl
Me
CH2Cl2 CH2Cl2 CH2Cl2 NH
N rt rt rt N
H
74% 89% 95%
J. D. Rainier et al., Angew. Chem. Int. Ed., 47, 5374 (2008)
 Fukuyama Group - Group Meeting Problems
05/09/2012

1
DPPA, Et3N
O NaN3, MsOH, rt; toluene, rt; TfOH NH
aq. KOH BnOH, reflux CH2Cl2, 0°C

68% 87% 79%

Y. Iwabuchi et al., Synthesis, 3418 (2011)

2
MeO Cr(CO)5 1) TFA
MeO OMe
O OMe
THF-H2O, rt
85% NHt-Bu
MeO OMe t-BuNC
O
neat, rt THF, rt 2) MeOH, 100 ºC
92% MeO
98% 85%

J. Barluenga et al., Chem. Eur. J., 8, 4149 (2002)

1) Co2(CO)8 1) I2, MeOH, rt H

CH2Cl2 rt, 92% 52%
BzO OH
TMS 2) furan, EtAlCl2 2) n-BuLi
CH2Cl2 THF, –78 °C
–20 to 0 °C, 77% 90% MeO

K. Tanino et al., Tetrahedron Lett., 52, 910 (2011)

4
NaH 4-chlorobutyronitrile O
N-methylaniline K2CO3 NaH
Adiponitrile C6H7NO
THF, reflux DMF, 80 °C DME, reflux N

98% 65% 25% NH2

H.-J. Liu et al., Tetrahedron, 59, 1209 (2003)

K. Sasaki et al., Tetrahedron Lett., 51, 903 (2010)
 Fukuyama Group - Group Meeting Problems
05/23/2012

1
DMAD, i-Pr2NEt
Cl 1-Me-imidazole CO2Me
O CH2Cl2, –10 °C to rt; CO2Me
H2O, rt

58%, Z/E = 79:21

Y. Wang et al., Org. Lett., 7, 2125 (2005)

2 1) O
Ph
OEt
O Ph CO2Me
reflux KOt-Bu HCl (gas) H
N 2) TsNHNH2 toluene, reflux MeOH, rt NH•HCl
H DME
0 ºC to reflux 60% 100%
80% (2 steps) dr = 3.5:1

J. D. Winkler et al., J. Org. Chem., 63, 9628 (1998)

3
O Me
Me hν DIBAL p-TsOH
O monocyclic
compound benzene O
MeCN/acetone (9/1) Et2O, –60 °C;
Me O Me 0 to 15 °C AcOEt, H2O reflux Me
H Me O
98% 50% (2 steps)
dr = 3:2

H. Takeshita et al., Bull. Chem. Soc. Jpn., 66, 2694 (1993)

4
O
O O Co2(CO)8, MS4A
toluene, rt; K2CO3 H
O
O
Me3NO•2H2O MeOH
H 0 °C to rt 0 °C to rt
CO2Me
69% 55%

J. D. Winkler et al., Org. Lett., 7, 1489 (2005)

 Fukuyama Group - Group Meeting Problems
06/05/2012
1
Me HO Me
O O
MeO O3, CH2Cl2, –78 °C; hν MeO O
H
MeO OMe Me2S, –78 °C to rt C6D6, 30 °C
MeO OMe
OMe 52% (2 steps)
OMe

E. I. Léon, E. Suárez et al., Angew. Chem. Int. Ed., 47, 8917 (2008)

2
Rh2(S-DOSP)4 (1 mol%) MeO2C OH
OH N2 heptane, rt to reflux;
+
Ph CO2Me Sc(OTf)3 (20 mol%)
reflux Ph
95%, 82% ee

H. M. L. Davies et al., Chem. Sci., 2, 2378 (2011)

3
TBSO
SO2Ph 1) NaOEt OTBS CO Et
CO2Et TfO 2
EtOH, rt
MeCN, rt; 86%
N NBn
O OBz BnMe3NCN 2) NaH, DMF N
MeCN 0 °C, 70% H
O HO
N
Bn 66%

E. Vedejs et al., J. Org. Chem., 65, 5498 (2000)

4
Ac2O (2.2 eq.) malononitrile Me CN
NH2 Et3N, DMAP NaOH

Me CO2H AcOH, 50 °C; H2O, rt Me N NH2

evap; H
83%

R. W. Fischer et al., Org. Process Res. Dev., 5, 581 (2001)

 Fukuyama Group - Group Meeting Problems
06/13/2012

1
NCS Me
CO2Bn 1,4-dimethylpiperazine (binap)Pd(SbF6)2 O
CH2Cl2, 0 °C; (20 mol%) O
TIPS
N Cl3CCO2H H2O (5 mol%) O
H TIPS C6H5Cl, 40 °C N
H
HO
95%, 92% ee
59%

M. C. Kozlowski et al., Angew. Chem. Int. Ed., 51, 2448 (2012)

2
O
Br Boc
Ph
O N
CO2Me CO2Me KOt-Bu K2CO3 MeNH2
+ MeN
THF, rt acetone, 40 ºC THF, 100 ºC CO2Me
NHBoc
90% 73% 61% Ph

J. Christoffers et al., Eur. J. Org. Chem., 1809 (2012)

3
LDA (2.6 eq) H
O O THF, 0 °C; PBu3 N
O
OEt
OEt THF O
N3 45 °C O

–78 °C to rt 64%

57%
P. Langer et al., Chem. Commun., 3044 (2003)

4
Ph Br
O MeMgBr
Et3N, Bu4NI Et2O, 0 °C to rt; HO2C OH
TBS
t-BuO
CH2Cl2-TFA-H2O CH2Cl2-Et2O TMSOTf, rt;
O Ph
rt reflux 1 M HCl aq.

50% (2 steps) 55%

J. S. Johnson et al., Org. Lett., 12, 944 (2010)

 Fukuyama Group - Group Meeting Problems
06/20/2012
1 O
NO2 EtO2C CO2Et
MgCl

THF, –70 °C; toluene, 80 °C CO2Et

Br
sat. NH4Cl aq CO2Et
74%
N
65%
(E:Z = 98:2) Br

G. Bartoli et al., J. Org. Chem., 55, 4456 (1990)

J. Yang et al., Angew. Chem. Int. Ed., 51, 5110 (2012)
2
1) Rh2(pfb)4 (cat.) O
N2 benzene, rt, 94%
O N
Ph 2) xylene, 145 ºC O
O O 68% N
O Ph

A. Padwa et al., J. Org. Chem., 68, 227 (2003)

3 O n-BuLi (1.1 eq) MeLi S

S THF, –78 °C; THF, –78 °C; SO2p-tol
O p-tol
CCl4, reflux TMSCl, –78 °C SO2, THF
Me Me Me
Me –78 to –70 °C
96% quant.
75%
S. E. Denmark et al., J. Org. Chem., 52, 4031 (1987)
B. Zwanenburg et al., Tetrahedron Lett., 32, 3867 (1991)

4 EtO2C
•
p-NsCl (3.0 eq.*) CO2Et Ph NO2
Ph CH2Cl2-pyridine, rt; Ph3P NH
OH C14H12N2O4S
H2N CH2Cl2, rt EtO2C
KOH, rt
CO2Et
97% 73% (trans:cis = 90:10)
(∗ theoretically 2 eq.)
J. Farrás et al., Tetrahedron, 57, 7665 (2001)
O. Kwon et al., J. Am. Chem. Soc., 131, 6318 (2009)
5 O
SO2Ph 1) 5% Na/Hg
NOH THF, rt, 75%
+
CO2Et toluene, reflux 2) n-Bu3SnH (5.0 eq) N
SO2Ph AIBN (2.0 eq) H
95% benzene, reflux O
(diastereomeric mixture) 83%

A. Padwa et al., J. Org. Chem., 75, 1992 (2010)

 Fukuyama Group - Group Meeting Problems
07/07/2012

1 KCN
Cl NO2 Cl
EtOH-H2O
reflux CO2H
10%
(73% SM recover)
von Richter, V. et al., Ber., 4, 459 (1871)
von Richter, V. et al., Ber., 4, 553 (1871)
J. F. Bunnett et al., J. Org. Chem., 21, 944 (1956)

2 O
1) hν, acetone, rt 3) RuO2, NaIO4 O H
75% CCl4, H2O, MeCN, rt; H
O C13H17NO2
2) DPPA, Et3N H
2 M aq. H2SO4;
HO2C 1,4-dioxane, reflux aq. NaHCO3
89% H
55%
O
J. K. Cowell et al., Tetrahedron Lett., 37, 2177 (1996)

3
1) CO (0.2 atm)
1) TBSOTf, Et3N [Rh(CO)2Cl]2 (cat.) H OH
Et2O, 0 °C, quant dioxane, 80 °C

2) CH2I2, Et2Zn 2) HCl, EtOH-H2O, rt

CH2Cl2, 25 °C, 86% 62% (2 steps) H
O O

Z. Yu et al., J. Am. Chem. Soc., 130, 4421 (2008)

4 O
SnBu3

R n-BuLi, THF, –105 °C to rt;

R
R R
(pin)B Me NMe2 Me
(Ghosez rgt)
Cl
reflux
R= 48%

V. K. Aggarwal et al., J. Am. Chem. Soc., 134, 7570 (2012)

 Fukuyama Group - Group Meeting Problems
07/11/2012

1
OH C6H4p-Br
N AgOTf (10 mol%)
O
p-BrC6H4 N
DMF, 75 °C
Ph Ph
83%

J. Wu et al., Org. Lett., 14, 3430 (2012)

2
CO2H Cl
1) conc HCl, reflux
82% NaOAc, H2O2 aq O

2) ClCO2Et, Et3N AcOH, 60 ºC O

THF, 0 ºC; Zn(BH4)2 HO
O 0 ºC, 85% 63%

G. Helmchen et al., Eur. J. Org. Chem., 2551 (2008)

3
O O
NH2OH·HCl MeN
NCS S
Me O H pyridine P O Me O H
Me DMF, rt; Ph Me
OHC Me CN Me HN NH
O MeOH, 45 °C A, NEt3 toluene O
THF, 0 °C 110 °C
O O
N 94% N A
65% 54%
Me Me

V. H. Rawal et al., J. Am. Chem. Soc., 133, 5798 (2011)

4 MeLi, ZnCl2
Me
Me
HO (HCHO)n Ni(cod)2 (10 mol%) Me
(COCl)2, DMSO, Et3N
CuI, i-Pr2NH CH2Cl2, –78 to –20 °C; Ti(Oi-Pr)4 O N
N H
1,4-dioxane B, DMAP THF O O
O N
reflux CH2Cl2, –20 °C to rt –20 °C to rt
O O
76% 62% 57% O
dr = 98:2
Me
Me
O N
PPh3Br
B J. Montgomery et al., J. Am. Chem. Soc., 121, 11139 (1999)
O O
 Fukuyama Group - Group Meeting Problems
07/18/2012

1 O CHN2
O
1) Rh2(OAc)4 1) Me3OBF4, CH2Cl2, 0 °C;
benzene, reflux evap.; NaBH4, MeOH, rt
N S 2) Raney Ni 2) ClCO2R, benzene, rt N
acetone, rt 38% (2 steps) RO2C
66% (2 steps)
R = p-MeOBn

S. J. Danishefsky et al., J. Am. Chem. Soc., 115, 30 (1993)

2 H H
1) NaH, Cl3CCN N
Et2O, 0 °C to rt Grubbs' cat (5 mol%) O
OH xylenes, 140 °C;
2) xylenes, reflux H Cl
50% (2 steps) styrene Cl
Ph
Cl
52%
dr = 1:1
M. L. Snapper et al., J. Am. Chem. Soc., 127, 16329 (2005)

3 NO2
Ph Ph cat. PdCl2(PPh3)2
I Ph cat. CuI, Et3N
+ O Ph
O2N butyronitrile, Δ Ph
Ph Ph
91% O

T. J. J. Muller et al., Chem. Commun., 4096 (2006)

4
Ph
hν Me3S(O)I (2.0 eq) H
CO2Et styrene NaH (2.0 eq)

O benzene, rt DMF, rt O CO2Et

O
H
78% 76% OH
3:2 mixture of
two isomers
S. Ohta et al., Org. Biomol. Chem., 3, 2296 (2005)
 Fukuyama Group - Group Meeting Problems
08/01/2012

1 O O
O Me
hυ conc. H2SO4 Me NHBn
CONHBn

Me THF, rt; THF-MeOH Me OMe

CO2Me evap. rt
O O
50%

P. S. Baran et al., Angew. Chem. Int. Ed., 45, 249 (2006)

2 Me OTES

S
(E/Z =4/1) N O3
O TESOTf
ZnCl2 CH2Cl2, –78 ºC; Et3SiH H H Me
Me IR Me O
H OH
CH2Cl2, 23 ºC PPh3 1827, 1714 cm–1 CH2Cl2
OBn O
–78 to 0 ºC OBn
83% 89%
(dr > 19:1) 66%

D. Romo et al., J. Org. Chem., 72, 9053 (2007)

3
Cl

Cl OMe
(1.2 eq.) O TMS
TMS Br n-BuLi (2.5 eq.) H2SO4

THF, –80 °C MeOH, 30 °C

Ph
Ph
81% 83%

M. Segi et al., Tetrahedron Lett., 51, 1294 (2010)

Me Me
AuCl3 (6 mol%)
O
O O CH3CN, rt
OH
90%

A. S. K. Hashmi et al., Chem. Eur. J., 3703 (2008)

 Fukuyama Group - Group Meeting Problems
08/08/2012

NO2
1 O2N Cl

90 °C;
Me2NH (2.2 eq), 0 °C to rt;

N cyclopentadiene, NaOMe, 125 °C

51-59%

K-P. Meinhardt et al., Org. Synth., 62, 134 (1984)

2 O
O CuSO4·5H2O (15 mol%) O
1) NH2NH2 1,10-phenanthroline (30 mol%) P
N CH2Cl2, rt K3PO4 N O

Br Ph Ph
O 2) O toluene, 135 °C
P O toluene, 60 °C
O Cl 84%
Et3N, CH2Cl2 47%
0 °C to rt

92% (2 steps)

K.A. DeKorver et al., Org. Lett., 14, 1768 (2012)

3
CO2H O
1) PMBO 1) TFA
H OH PPh3, DEAD CH2Cl2, rt O
THF, 0 ºC, 82% 70 % HO H
tricyclic
EtO2C compound
O N 2) o-dichlorobenzene 2) MsCl, Et3N N
150 ºC, 73% (except for PMB group) CH2Cl2, 0 ºC;
evap.;
H2, Pd/C
MeOH, rt, 20%

A. Brandi et al., Org. Lett., 2, 2475 (2000)

4
O
EtO2C NO2
(2.0 eq) BnHN O
Ph N Ph N
BnNH2
reflux
NHBn
O
86%

S. Umezawa et al., Bull. Chem. Soc. Jpn., 36, 1150 (1963)

 Fukuyama Group - Group Meeting Problems
08/22/2012

1 TsN3, CuI, TBAI, K2CO3

Ph O
CH2Cl2, rt;
TsN neutral Al2O3 TsN
Ph
77%

Y.-Q. Tu et al., Chem. Sci., 3, 1975 (2012)

2 O
3) Me
Cl

OTBDPS OTBDPS
Me 1) PhSH, Et3N i-Pr2NEt Me
THF, 70 ºC CH2Cl2, rt
Me 95% tricyclic 92% Me
O compound
O
2) TMSOTf, 2,6-lutidine (except Ph) 4) O N H
O
H2N O CH2Cl2, –78 to 0 ºC t-amyl O Ph
NBoc N O
98% t-BuPh, 120 ºC
62%

A. G. Myers et al., J. Am. Chem. Soc., 127, 5342 (2005)

3

HO Br2 (theoretically 3 eq.) O

Sodium tetraborate O
O
O THF-NaOH aq.
0 °C O

13%

T. Rosenau et al., Eur. J. Org. Chem., 2011, 3036 (2011)

F O
Me OH [Rh(OH)(cod)2] (2.5 mol%) 1) TsOH (5 mol%) F
Ligand (6 mol%) CH2Cl2, 23 °C H O PPh2
Me2Si
H O PPh2
F
mesitylene, 100 °C 2) toluene, 80 °C SiMe2 F O
71% (2 steps) Me
75%, 99%ee, dr=19:1 Ligand

N. Cramer et al., Angew. Chem. Int. Ed., 49, 10163 (2010)

 Fukuyama Group - Group Meeting Problems
09/05/2012

1
BnNH2, PhH
reflux (Dean-Stark); 2,2-dimethoxypropane POCl3 CO2Me
O
evap.; p-TsOH (cat.) pyridine MeO
O C19H21NO4
maleic anhydride MeOH MeCN
O reflux 60 °C N
THF, 0 °C Bn
91% (2 steps) 82%

G. Revial et al., J. Org. Chem., 67, 2252 (2002)

2
ClO4
S N Mes
O
CHO (5 mol%)
CHO O
DBU (20 mol%)
+
O THF, 80 °C O
Cl
OMe
60% OMe Cl

F. Glorius et al., Org. Lett., 13, 5624 (2011)

3 O O

Cl Cl
S
Br Br Pd/C, H2, rt NH
NH Zn dust toluene filt., evap.; H
Et
NO2 –78 to 25 ºC 120 ºC LiAlH4, THF
reflux, 83% N
72% 66% (dr= 1: 0.73) Et

A. Padwa et al., J. Org. Chem., 74, 7389 (2009)

4
Me
O CO2Et
CO2Et
K2CO3 N
Br S
H2N
EtOH, reflux
SH
60%

B. Zhao et al., Synthesis, 3133 (2011)

 Fukuyama Group - Group Meeting Problems
09/26/2012

1
HO HO
MsOH
microwave
HO
O
NMe 90 °C
NMe
H
75%
HO

A. E. Arppe, Justus Liebigs Annalen der Chemie, 55, 96 (1845)

J. L. Neumeyer et al., Synth. Commun., 38, 866 (2008)

2
O
O O N cat. ZnCl2 Me
+ O Ts
Me Me ClCH2CH2Cl, 60 °C
H Me O NTs
70%

L. A. Lopez et al., Angew. Chem. Int. Ed., 51, 8063 (2012)

3
S8 (0.25 eq.) NaOH aq.
O Et3BnNCl
morpholine (3 eq.)
p-TsOH (cat.) 100 °C; OH
C12H14BrNOS
120-130 °C; HCl aq. O
Br Br
78%

S. R. Adapa et al., Synth. Commun., 33, 59 (2003)

Rh2(OAc)4 (1 mol%)
N2 toluene, 60 °C; Ph
OMe + PhS SPh
Ph [RuCl2(p-cymene)]2 (5 mol%) MeO O
O 80 °C

81%
J. Wang et al., Angew. Chem. Int. Ed., 46, 1905 (2007)
 Fukuyama Group - Group Meeting Problems
10/06/2012

1
N2 O Ph
O O microwave
+ Ph O + BnNH2
toluene, 140 ºC NBn
73% O

J. Rodriguez et al., Org. Lett., 12, 4212 (2010)

2
H O
1) PhI(OAc)2 (1.2 eq.)
HO OMe
HFIP, 0 °C OMe
O Si O O
MeO OH 2) TBAF, THF, rt

40% (2 steps)

S. Canesi et al., J. Org. Chem., 77, 7588 (2012)

O p-TolSO2Na PhCH2Br TBAF

Ph
TBS I O
DMF, rt NaHMDS, THF THF
–80 to –60 °C –80 to –70 °C
80%
93% 86%

K. Takeda et al., Org. Lett., 6, 4849 (2004)

4

MeO OTES Rh2(OAc)4 O

PhCH2N3, BF3·OEt2

–78 °C to rt CH2Cl2, 0 °C to rt N
CH2Cl2 Ph
90%
47%

J. Aube et al., Org. Lett., 2, 1657 (2000)

 Fukuyama Group - Group Meeting Problems
10/13/2012

(pin)B–B(pin) (3 eq)
1 Cu(OAc)2 (2 mol%) Ph
MeO P(t-Bu)3 (7 mol%) PhCHO (3 eq) OH OH
C28H52O8B4
OMe toluene, 80 °C 1H NMR (CDCl)3 toluene, 100 °C Ph Ph
δ 1.12 (s, 24 H)
62% 1.26 (s, 24 H) 86%
1.85 (s, 4 H)

H. Yoshida et al., Angew. Chem. Int. Ed., 51, 235 (2012)

T. Hiyama et al., Chem. Asian. J., 2, 1142 (2007)

2 1) MeO

Li OMe
H2O2, Na2CO3 O
THF, –78 °C dioxane-H2O NaOH
Et O HO OMe
52% 60 °C; The intermediate CuSO4
contains
2) toluene, reflux; HCl aq. 5-membered ring. H2O, 70°C
t-BuO O Me
Ag2O, K2CO3, rt H2SO3 aq.
92% 0 °C; 72% O OMe
3) TFA, toluene, 0 °C
quant.

H. W. Moore et al., J. Org. Chem., 60, 461 (1995)

3
Me COCF3 Me3S I, n-BuLi MeS CF3
N THF, –20 °C to rt;

Ph O O AcOH, 80 °C Ph N
Me
70% (2 steps)

M. Kawase et al., Tetrahedron Lett., 53, 2782 (2012)

4
O
Br
1) MeO Cl 1) Me
Et3N, CH2Cl2, rt In (powder) OMs
N 2) p-TsOH•H2O THF-NH4Cl aq, 0 ºC Me
THF-H2O, reflux 77%
Monocyclic H H H
Compound MeO
3) NaIO4, NaHCO3 aq 2) MsCl, Et3N
O O CH2Cl2, rt H
hydroquinone N
53% (3 steps) toluene O
190 ºC (sealed tube)
47%

B. Alcaide et al., Eur. J. Org. Chem., 98 (2005)

 Fukuyama Group - Group Meeting Problems
10/31/2012

1 O
O SPh2•BF4
KOH TiCl4 N

DMSO CH2Cl2
N3 0 °C to rt –78 °C to rt

78% (2 steps)

S. Baskaran et al., Chem. Commun., 48, 5778 (2012)

2
1) BF3·OEt2
O O Ph
Me CDCl3, rt
quant. Me
Ph
O
Ph 2) TfOH (20 eq.)
Me CDCl3, 30 °C Me
O 98% O

T. Oshima et al., Eur. J. Org. Chem., 3917 (2012)

3
O TMS
N2 O
O Rh2(esp)2 (0.5 mol%) TBAF
O
CH2Cl2, rt THF, 45 ºC O
O 71% 63%

J. A. May et al., J. Am. Chem. Soc., 134, 17877 (2012)

4
Ph
[(JohnPhos)Au(CH3CN)][SbF6]
n-BuLi, THF, –78 °C; (5 mol%)
OMe TMSOTf; Ph
spiro
(OC)5Cr compound
Ph , CH3CN DCE, 100 °C, μ W
Ph
73% 41%

J. Barluenga et al., Angew. Chem., 124, 10523 (2012)

 Fukuyama Group - Group Meeting Problems
11/10/2012

1 Ph BF3K
HO Bn La(OTf)3 (10 mol%) NsNHNH2
NsNHNH2 AuCl (1 mol%) Et3N
O O Ph O Bn
MeCN, rt THF, rt CH2Cl2, rt H H
Me Me
88%, dr = 2:1 83% 72%

R. J. Thomson et al., J. Am. Chem. Soc., 134, 5782 (2012)

2 O Me
1) NaOH aq. MeCHO H
O
EtOH, rt, 60% SnCl4 O
2) t-BuOK, MeI CH2Cl2
t-BuOH, rt, 80% 0 °C
Me
83%

F. Schoenebeck et al., Angew. Chem. Int. Ed., 51, 5647 (2012)

P. Shanmugam et al., Tetrahedron, 52, 7737 (1996)
H. Saito et al., Bull. Chem. Soc. Jpn., 39, 694 (1966)

3
CO2Me

CO2Allyl
Ph
O Yb(OTf)3 (2 mol%) Pd2(dba)3 (6 mol%) N
+ PhNHOH
Ph
Ph toluene, 40 ºC MeCN, 80 ºC;
DBU, 60 ºC CO2Me
68%
82%

M. A. Kerr et al., Angew. Chem. Int. Ed., 51, 11088 (2012)

4 HO
3) Et2SBr·SbBrCl5
OBoc 1) AllylTMS, BF3·OEt2 MeNO2, –25 °C to rt O
CH2Cl2, –78 to –20 °C 72%

O 2) MsCl, Et3N 4) DIBAL, toluene Br O H

Me CHO CH2Cl2, 0 °C to rt –78 °C to rt
81% (2 steps) 46% Me

S. A. Snyder et al., J. Am. Chem. Soc., 134, 17714 (2012)

 Fukuyama Group - Group Meeting Problems
11/17/2012

1
O O O
CH2(ZnI)2 (1.2 eq)
O O THF, 25 °C

78%

M. Sada, S. Matsubara, J. Am. Chem. Soc., 132, 432 (2010)

2 O
O
O Cl Me3OBF4
CN Et3N MeNO2, rt; H
N N
O CH2Cl2, rt NaBH(OAc)3
0 °C to rt N O
H Me
69% OH
61%

S. A. Habay et al., J. Org. Chem., 77, 10416 (2012)

3
H
1) LDA (1.05 eq) 3) NaIO4, CH2Cl2/H2O N OH
N THF, rt, 50% rt, 59% (2 steps)

Br 2) OsO4 (10 mol%) 4) AlCl3 (3 eq), DCE

MsNH2 (3 eq) rt, 21% (20:1>dr)
Me3NO·2H2O (5 eq) O
O t-BuOH/THF/H2O O
O rt

M. Lautens et al., J. Am. Chem. Soc., 134, 15572 (2012)

4
N
H Sc(OTf)3
CO2Me microwave
+ + CHO
O O
N H H2N CH3CN, rt to 125 °C
N
Boc H
82% O

O. Reiser et al., Angew. Chem. Int. Ed., 51, 4722 (2012)

 Fukuyama Group - Group Meeting Problems
11/24/2012

1
Br n-BuLi NBS (1.0 eq) CHO
THF, –78 ºC; THF-H2O, rt;

O PhCHO 1 M HCl aq. O Ph

90% 72%

P. J. Walsh et al., J. Am. Chem. Soc., 130, 4097 (2008)

2
O PdCl2 (10 mol%) O
DMP TfOH (30 mol%) O
Ph Ph
.
CH2Cl2, rt CH2Cl2, rt
Ph Ph
91% 88%

L. Wu et al., Org. Lett., 14, 2718 (2012)

3
CO2Me O
PhNO (2.4 eq)
OTBS AcOH (2.4 eq) H CO2t-Bu
CO2Me
t-BuO MeOH toluene*, 80 ºC
–78 ºC to rt
61% N
64%
*containing water (trace)

J. Yang et al., Angew. Chem. Int. Ed., 51, 5110 (2012)

4
Me OH SMe
MeS
SMe SnCl4 (3 eq.) Me
Me MeS
MeNO2
0 °C to rt 4-MeOC6H4 H Me
4-MeOC6H4
78%

H. Junjappa et al., J. Chem. Soc., Perkin Trans. 1, 1547 (2000)

 Fukuyama Group - Group Meeting Problems
12/12/2012

1
1) N 4) Et3SiH, TFA
2 CO2Me
O CH2Cl2, 0 °C to rt O
Rh(OAc)4, CH2Cl2, rt, 60% 92% O
O
2) NBS, H2O/dioxane, rt, 66% 5) H2, Pd/C
OBn 3) K2CO3, MeOH, rt, 94% MeOH, rt, 97% OH
R. S. Perali et al., Tetrahedron, 68, 3725 (2012)

2
1) MeS-SMe2•BF4
MeCN, –40 °C;
Ph O O OCOt-Bu Et3N Me
64% N SMe
SMe O
N 2) benzene
Me SMe reflux O
Ph
61%
A. Padwa et al., Heterocycles, 58, 227 (2002)

3
1) NaOH
Li H2O2
Ph
THF-H2O, rt
Et2O, –78 °C; 81% (2 steps) BF3·OEt2 CHO
W(CO)6 C29H41BO
2) PPTS CH2Cl2 Ph
CH2(OMe)2 –15 °C
rt
2 BCl 90%
Et2O
–78 °C to rt
J. Barluenga et al., Org. Lett., 5, 905 (2003)

4
1) 2-Bromoethanol 3) BrCN, NaHCO3 EtO
EtOH, 80% MeOH, 0 ºC, 50% OMe
N N O
2) Ethyl vinyl ether 4) BnBr, MeCN; evap.; BnN N
CaCO3, H2O, rt NaBH4, MeOH, rt NC
90% 50%
Y. Langlois et al., Tetrahedron Lett., 36, 9475 (1995)
 Fukuyama Group - Group Meeting Problems
12/19/2012

1 DMSO
HCl (gas) DMDO (1 eq) Ac2O
N
C15H14N2
AcOH acetone acetone N
NH2
rt rt rt
53% quant 77%
X. Qian et al., Synthesis, 8, 1228 (2005)
M. Harmata et al., Eur. J. Org. Chem., 7053 (2012)

2
chloroacetonitrile (2.5 eq.)
AlCl3 (1.2 eq.)
BCl3 (1.2 eq.) AllylMgBr (2.5 eq.)
NH2 N
CH2Cl2 THF H
Cl 0 °C to reflux –10 °C to rt Cl

64% 89%
Tao Pei et al., Tetrahedron, 65, 3285 (2009)

3 1)
HO
OH OMe
OMe
p-TsOH (cat.) 3) PhSO2Cl, Et3N MeO
MeO toluene, reflux CH2Cl2, 0 ºC to rt
77% 82%

O 2) LiAlH4 4) Li, NH3 NMe

NHCO2Me THF, reflux t-BuOH-THF, –78 ºC H
O
95% 76%
OMOM
O
K. Ogasawara et al., Org. Lett., 4, 4515 (2002)

4
1) TESOTf
Cl 1) n-BuLi (5 eq) Et3N
O Ar N N Ar
THF, –35 °C CH2Cl2, rt
H TESO
95% 95% Au SbF6–
C15H24O2
O NCPh
2) NaBH3CN 2) catalyst
O Ar=2,6-(i-Pr)2C6H3
BF3•OEt2 CH2Cl2, rt H
CH2Cl2, rt, 74% 65% catalyst
3) DMP, H2O
CH2Cl2, 0 °C to rt
86%
A. M. Echavarren et al., Chem. Commun., 7327 (2009)
 Fukuyama Group - Group Meeting Problems (Nagoya)
01/08/2013

N
F Ph N
(10 mol%) O
OMe Ph
O + O
TMSO MS4Å O O
O
THF OMe
–78 ºC to rt O

89%
dr = >20:1

D. W. Lupton et al., J. Am. Chem. Soc., 135, 58 (2013)

2
SO2Ph
SO2Ph
Br2 toluene Me H
H C19H21NO3S
N
O MeOH reflux N
Me H2O H O
C19H23NO3S 0 °C 70%

77%

D. Y. Gin et al., Chem. Eur. J., 14, 1654 (2008)

Ph
BF3•OEt2 (1.0 eq) O
O Ph
Ph + OH
Ph benzene
1 eq 1.2 eq rt
Ph
65%

A. K. Saikia et al., Synlett, 233 (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
01/16/2013

O N N
Me Ph toluene
reflux OH Me
42%

S. Kim et al., Tetrahedron Lett., 35, 8405 (1994)

2
O

O O 1) aq NH3 OMe
MeOH
Ph NH
2) Pd/C, H2
MeOH
90% (2 steps)

R. J. K. Taylor et al., Angew. Chem. Int. Ed., 52, 1490 (2013)

3
O O
O2
O hv O

BHT (5% mol)

CH2Cl2 H H
4d
61%

H.-G. Schmalz et al., Angew. Chem. Int. Ed., 51 6000 (2012)

 Fukuyama Group - Group Meeting Problems (Nagoya)
01/24/2013

1
Me

OH 2 mol% AuCl3 OEt

Me O
EtOH, rt

96% Me

J. Barluenga et al., Angew. Chem. Int. Ed., 45, 2091 (2006)

2
ONs Pd2(dba)3·CHCl3
(0.04 eq)
TMSO Ph3P (0.1 eq) TMSO
Me HCO2H (4 eq) Me NNs
NNs
Et3N, THF, rt
H 92% H

S. Aoyagi et al., Org. Lett., 14, 6374 (2012)

3 O
MeO

(1 eq) O

OH OMe
+ OMe DDQ (2.0 eq) H

o-dichlorobenzene
150 ºC O
HO 60%
O
OMe
O OH

(1.5 eq) J. A. Porco Jr. et al., J. Am. Chem. Soc., 134 19782 (2012)
 Fukuyama Group - Group Meeting Problems (Nagoya)
01/30/2013

1
TMSOTf (cat.) O
OAc OTBS 2,6-DTBMP
Bn
O CH2Cl2, –78 ºC Bn
O
H H
99%

S. D. Rychnovsky et al., J. Am. Chem. Soc., 48, 15663 (2004)

LHMDS (1.05 eq)

DMF Br
N –15 to –10 °C; N
S O NBS (1.0 eq) S O
–78 °C

79%

R. A. Buzon et al., Org. Synth., 87, 16 (2010)

 Fukuyama Group - Group Meeting Problems
05/11/2013

1
PhLi p-TsOH RuO2•H2O (cat.)
Me Me (4.0 eq) (cat.) NaIO4 Me Me
CO2Me
AcHN THF, rt toluene MeCN, CCl4 AcHN CO2H
reflux H2O, rt
89%
98% 44%

C. López et al., Tetrahedron: Asymmetry, 16, 2593 (2005)

2 Me
N
Me
O O
H2N
O
N O
Pd(PPh3)4 O
CHO Na2SO4 PdCl2(CH3CN)2 i-Pr2NEt H
H
O
I THF, 50 °C CHCl3, 60 °C DMA, 100 °C N
H
93% 99% 98%

M. Sasaki et al., Tetrahedron Lett., 48, 4255 (2007)

3 CHO
O
CO2Et
MeO O Me
LiOi-Pr Ph OMe
Me (25 mol%) Cs2CO3 O
C
acetone, rt CO2Et
PhO2C SiEt3 THF, –10 °C
Ph
68% 81%

P. Maity, S. D. Lepore, J. Am. Chem. Soc., 131, 4196 (2009)

 Fukuyama Group - Group Meeting Problems
05/18/2013

1
CO2H
EtCHO O
MeOH, rt;
NHBoc evap; NPMB
Et
AcCl, MeOH, rt
N
PMBNH2 H O
79%
NC
C. Hulme et al., J. Org. Chem., 63, 8021 (1998)

2
1) CDCl3, reflux O
OH
80%

OH 2) KH (2 eq)
18-crown-6 (2 eq)
THF, rt
90%

M. E. Jung et al., Org. Lett., 3, 3025 (2001)

3
O
EDCI, Et3N
O
EtO NCS CH2Cl2 O H
Et3N 0 °C to reflux; N
TFA·H2N O
OAllyl HN
CH2Cl2, rt NaOMe, MeOH
Ph 0 °C to rt Ph
89%
70%

J. J. Tepe et al., J. Org. Chem., 74, 3406 (2009)

 Fukuyama Group - Group Meeting Problems
05/25/2013

1
LHMDS
Ph
O THF, –78 ºC; KOt-Bu toluene
O Ph THF, –78 ºC 60 °C O
Ph PhNTf2
DMPU
98% (2 steps)
75%

G. Minehan et al., J. Org. Chem., 76, 3576 (2011)

2
Cl3CCONCO
CH2Cl2, 0 °C; PPh3, CBr4, Et3N
HO evap.; CH2Cl2, –20 °C*; Me
OTBDPS OTBDPS
Me K2CO3 AlMe3, hexane, –20 °C NHAc
MeOH/H2O (2:1)
0 °C to rt 93%

99% * Draw the transition state.

Y. Ichikawa et al., J. Chem. Soc., Perkin Trans. 1, 2791 (1994)

3
PhNMe3+Br3– (0.1 eq) Me3SO+I– (10 eq)
TsN
TsNClNa (1.1 eq) NaH (10 eq)
OH C3H7
CH3CN, rt, 12 h DMSO, 85 ºC, 24 h
OH
97 % 44%

K. B. Sharpless et al., J. Am. Chem. Soc., 120, 6844 (1998)

D. M. Hodgson et al., Chem. Commun., 3226 (2006)
 Fukuyama Group - Group Meeting Problems
06/01/2013

1
Ts
OTf N
Ts CsF H
+
N
dioxane H
TMS 110 ºC

95%

R. P. Hsung et al., Org. Lett., 11, 3666 (2009)

2
Br n-BuLi, THF NBS (1.0 eq.)
CHO
–78 ºC; THF-H2O (4:1), rt;

PhCHO 1 M HCl aq. Ph

O –78 ºC O
72%
90%

P. J. Walsh et al., J. Am. Chem. Soc., 130, 4097 (2008)

3 OBn
OBn
OBn OH OBn OH
TMS n-Bu4NOH

toluene, 100 ºC hν, THF DMF, –20 ºC

N3 N
OBn 80% (2 steps) 77% 49% OBn H

M. Ciufolini et al., Angew. Chem. Int. Ed., 41, 4688 (2002)

 Fukuyama Group - Group Meeting Problems
06/12/2013

1 O
O
HHN O
Me HHN O TFAA, pyridine Me
N
O N OMOM
OMOM CH2Cl2
H
H 65%
O CF3

A. S. Kende et al., J. Am. Chem. Soc., 117, 10597 (1995)

2
ClCO2Et, Et3N
O THF, –30 ºC; p-TsOH•H2O (cat.)
O
CO2H toluene N
O O reflux O O
NH2
–10 ºC to rt 83%
89% (2 steps)

C. H. Heathcock et al., J. Org. Chem., 57, 2531 (1992)

3
S
P
EtO SH
EtO
O NH2OH•HCl, NaOAc S
Ph
Ph 1,4-dioxane N
H
90 °C

89%

L. D. S. Yadav et al., Tetrahedron Lett., 53, 7113 (2012)

 Fukuyama Group - Group Meeting Problems
06/19/2013

1
Me
Me AuCl Me
OH O (10 mol%) Me
Me O
CH2Cl2
Me Me rt H OH
Me
48%

D. Ma et al., Angew. Chem. Int. Ed., 49, 3513 (2010)

2
NO2 N Cl
POCl3 (3 eq.*)

MeO N SMe MeCN MeO N SMe

H 80 °C

70%
(* theoretically 2 eq.)

H. lla et al., Org. Lett., 7, 2169 (2005)

3
PhCHO O
CN MeOTf LHMDS Ph

NBn CH2Cl2 THF neat, vacuum N Ph

0 °C –78 °C 50 °C
Me
83% 98% 81%

O. David et al., Chem. Commun., 2500 (2007)

 Fukuyama Group - Group Meeting Problems
06/26/2013
1 i-C5H11ONO
O TiCl4
Me
OMe
O
TMSNTf2 H
LDA, TMSCl t-Bu t-Bu
OMe
toluene THF, –78 ºC CH2Cl2 N
0 ºC –45 to –15 ºC O
H
92% 71% (2 steps)

A. Zakarian et al., J. Am. Chem. Soc., 128, 5356 (2006)

2
NsHNNH2
HO O Br
La(OTf)3 (10 mol%) NBS
Ph BF3K +
O OH MeCN, rt CH2Cl2, rt Ph O
86% 58%

R. J. Thomson et al., J. Am. Chem. Soc., 134, 5782 (2012)

3
1) HCHO aq.
NO2 i-Pr2NEt OH
MeCN, rt DABCO

2) Ac2O, DMAP o-Cl2C6H4 OAc

CH2Cl2, rt reflux
37% (2 steps)
72%

S. Z. Zard et al., Org. Lett., 7, 3489 (2005)

 Fukuyama Group - Group Meeting Problems
07/03/2013

1
O PhCN (10 eq.) H
N
TsNHNH2 Et3N, DBU AgSbF6 (10 mol%) Ph
EtO CH2Cl2, 0 ºC CH2Cl2, 0 ºC CH2Cl2, rt
OEt
O O
73% (2 steps) 62%

Y. Lou et al., Org. Lett., 15, 1421 (2013)

2
Me hν
1) Li, liq. NH3, Et2O Me
–78 °C, 92% Me acetophenone (0.3 eq.)
O
2) 2-chloroacrylonitrile acetone, rt
MeO
benzene, 80 °C, 75% O O H
OMe 61%
3) Na2S•9H2O
EtOH, reflux, 92%

K. Schaffner et al., Angew. Chem. Int. Ed., 21, 820 (1982)

S. V. Ley et al., Tetrahedron, 45, 7161 (1989)
D. A. Evans et al., Tetrahedron Lett., 13, 121 (1972)

3
MeMgBr, CuI (20 mol %) O
THF, 0 ºC to rt; OH
O
tBuO
O
tBuO
TBS OTBS
O
63%

J. S. Johnson et al., J. Am. Chem. Soc., 128, 9302 (2006)

 Fukuyama Group - Group Meeting Problems
07/10/2013

1
O O
Me3S(O)I, NaH 28% NH3 aq NaNO2, AcOH
O
O THF dioxane, 120 ºC H2O, 0 ºC

27% (3 steps)

M. Inoue et al., Tetrahedron. Lett., 50, 1035 (2009)

2
O CHO
TMS t-BuLi

O Ph THF-HMPA (25:1) BnO TMS

–78 ºC

40%

M. E. Jung et al., J. Org. Chem., 61, 9065 (1996)

3
Ph Ph
H O
CHO
N
N
o-dichlorobenzene
220 ºC (µwave)
H
73%

C. D. Vanderwal et al., J. Am. Chem. Soc., 131, 7546 (2009)

 Fukuyama Group - Group Meeting Problems
07/13/2013

1
O
O
1) vinylmagnesium bromide 3) OsO4, NMO
THF, 0 ºC t-BuOH, H2O, rt
CHO
I 2) CuCl (10 mol%) 4) NaIO4, THF/H2O, rt
2-aminopyridine (10 mol%) O
N
NaOMe/MeOH (25 wt%) >75% (2 steps) N
Bn diglyme, 130ºC Bn
77% (2 steps)
S. Kobayashi et al., Tetrahedron Lett., 48, 1805 (2007)

2
SPh2
KOt-Bu
O DMSO, rt; NaOMe
t-BuO2C
t-BuO2C LiBF4 MeOH MeO2C
CO2Me
benzene, rt reflux
CO2Me
82% 74%

B. M. Trost et al., J. Am. Chem. Soc., 99, 6124 (1977)

3
O
O Ts DMAP (55 mol%)
N Ph
+ O2N
Ph CH2Cl2, rt
O2N N
Ts
70%

S. Xue et al., J. Org. Chem., 73, 8491 (2008)

 Fukuyama Group - Group Meeting Problems
07/24/2013
1

SmI2 (3.0 eq), LiBr (12 eq)

H2O (8.0 eq)
BnO THF BnO O
O –78 to –30 °C;
N CO2Et N
BnO + Me2PhSi BnO
Zn
BnO (1.4 eq) AcOH BnO H SiMe2Ph
–30 to 80 °C

49%

S. Py et al., Org. Lett., 14, 1042 (2012)

2
1) maleic anhydride
hydroquinone
neat, 170 °C PhSO2N3 AcO
quant. benzene, rt; PhO2SHN H
OMe 2) (Ph P) Ni(CO) OMe AcOH OMe
3 2 2
MeO2C diglyme, reflux CO2Me CO2Me
81% 75%

K. Wiesner et al., Can. J. Chem., 51, 1448 (1972)

3
1) Ti(Oi-Pr)4 MeO
EtMgBr (2 eq) MeO Br
THF, 5-10 °C AIBN H
O O
95% TiCl4 n-Bu3SnH
OMe
2) TMSOTf CH2Cl2 benzene
H
2,6-lutidine –40 °C to rt reflux OMe
CH2Cl2, 0 °C
88% 71% 99%

J. K. Cha et al., Org. Lett., 4, 3707 (2002)

 Fukuyama Group - Group Meeting Problems
08/03/2013

1 O
TBSOTf
Et3N
A
H13C6 O CF3 Et2O
–78 °C to rt

H 1) LDA, TESCl 2,6-lutidine O

THF, –78 °C TFAA CO2Me
MOMO · (CH2)5CO2Me
2) s-BuLi THF F3C
THF, –78 °C; –78 to –40 °C
H A, –78 °C TBSO
55% (2 steps) 58%
(Z:E = 2.6:1)

M. A. Tius et al., J. Org. Chem., 63, 5971 (1998)

2 SiMe2Ph ∗t-OcNC (8 mol%) c-HexCHO

Ph2Si Hex OH Hex
Pd(acac)2 (2 mol%) TiCl4
O
c-Hex
toluene, rt to reflux; CH2Cl2, –78 ºC
Me n-BuLi Me
96.7% ee THF, –78 to 0 ºC 76% 93.2% ee
(syn:anti = 95:5)
86%

∗t-OcNC NC
= t-Bu
Y. Ito et al., J. Org. Chem., 61, 4884 (1996)

3
O Tf2O O
TFA, MS4A CH2Cl2;
Boc N
N
CH2Cl2 evap.;
OBoc 15% KOH aq.
90%
75%

J. Aubé et al., J. Org. Chem., 68, 8065 (2003)

 Fukuyama Group - Group Meeting Problems
08/21/2013

1 O
Rh2(OPiv)4
O (5 mol%) Ph O
Ph H
O Ph toluene, 110 ºC Ph

79% (dr = 93:7)

J. M. Fox et al., Org. Lett., 15, 1500 (2013)

2
NaNO2*
chloroxime
EtO2C NH2•HCl (C4H6ClNO3)
HCl aq.
(C4H9NO2•HCl) –5 °C

54%
* theoretically 2 eq.

chloroxime H2, Pd/C

NaHCO3 AcOH
NHCbz CO2Et
N
EtOAc, rt MeOH/H2O (5:1) H
40 °C
97%
95%
Y. Hu et al., Org. Lett., 14, 1062 (2012)
A. Thorarensen et al., Bioorg. Med. Chem. Lett., 17, 2347 (2007)

3
1) TFAA, TFA
CH2Cl2, 0 ºC
89%
2) mCPBA (1.0 eq.) O
O
hν CH2Cl2, –78 ºC S
HO Pyrex® 82%
hemiketal
MeCN 3) BF3•OEt2 O
S
0 ºC TFAA
O SiMe3
98% CH2Cl2, 0 ºC
51%

J. D. Winkler et al., J. Am. Chem. Soc., 128, 9040 (2006)

 Fukuyama Group - Group Meeting Problems
08/31/2013
1
O2, Rose Bengal O
hν, MeOH, 5 ºC; N
O Me2S, rt;
H
MeO OH
; MeO
O NH2
MeO OMe
BF3•OEt2, CH2Cl2
–78 ºC to rt

57%

G. Vassilikogiannakis et al., Org. Lett., 15, 3714 (2013)

2
Grubbs 2nd

TMSCl, Et3N O Ph OH
O
CH2Cl2, –78 ºC; CH2Cl2, reflux;
CO2Et O O
PhCH(OAllyl)2 Rh2(OAc)4 (cat.), rt;
N2 EtO2C
BF3•OEt2, –78 ºC NaBH3CN, AcOH
THF, 0 ºC to rt Me
92%
26%

D. M. Hodgson et al., Org. Lett., 10, 5553 (2008)

NO2 1) AcOH-H2O (3:2)

reflux, 76% DBU
C11H14Cl2O CO2Me
2) Ph3P (2.0 eq.*) PhCl MeOH
CO2Me CCl4 (1.0 eq.*) reflux reflux
THF, reflux, 51%
43% 58%
* theoretical amount

S. Zard et al., Tetrahedron, 67, 9844 (2011)

 Fukuyama Group - Group Meeting Problems
09/18/2013
1
1) O
S
tol Me

PivO LDA, THF PivO

–78 °C
2) TMSCl, KHMDS (EtO)3P
THF, –78 °C 2,4,6-collidine O
PMBO CHO 3) LDA, THF O OH
O MeO OH
–78 °C
150 °C
O O >65% (3 steps) O O
91% PMBO

A. Zakarian et al., Org. Lett., 7, 1629 (2005)

2
O
O
1) TsCl, Et3N N
N NH O CH2Cl2, rt, 83%
H
HN O
OMe 2) 1,2-dichlorobenzene O
N O HO 180 ºC N
Me Me H
EDCI, DMAP 74% CO2Me
CH2Cl2, 0 ºC to rt
87%
D. L. Boger et al., Org. Lett., 7, 741 (2005)

OMe propionaldehyde 1) CH(OMe)3, TMSOTf OMe O O

i-PrO SmI2 (50 mol%) CH2Cl2, 0 °C i-PrO
O OH O O
THF, –10 °C 2) Jones reagent
MeO n-Pr acetone, 0 °C MeO n-Pr
90%
85% (2 steps)

X. She et al., J. Org. Chem., 78, 6338 (2013)

 Fukuyama Group - Group Meeting Problems
09/24/2013

1
O
O Ph3SnH, AIBN Me

Me toluene, reflux Me
TESO Me OTES
79%

A. Nishida et al., Tetrahedron Lett., 36, 3015 (1995)

CF3
Cl
F3C CDI
Cl
OH MeCN N
rt Ph
NHTr Ph
93%

L. F. Frey et al., J. Am. Chem. Soc., 122, 1215 (2000)

3
Br Br
Br
PhI(CN)OTf (1 eq*)
NH i-Pr2NEt (2 eq*) CAN (2.0 eq) H H
Br H N N
N N O
SPh MeOH-CH2Cl2 H2O-MeCN
O O N N
N H
H 56% 62%

* theoretical amount

K. S. Feldman and A. P. Skoumbourdis, Org. Lett., 7, 929 (2005)

 Fukuyama Group - Group Meeting Problems
10/05/2013
1
O Ph(CH2)3N3 O
Me Me BF3•OEt2 Me
N Ph
CH2Cl2
Ph –78 °C Ph Me

80%

F. G. West et al., J. Am. Chem. Soc., 129, 12019 (2007)

2
H2, Pd/C OH
OMe O O
SnCl4 Boc2O
O
MeCN MeOH, rt H OMe
N –30 °C to rt NHBoc
O Bn 82% O
68% dr = 7:1

H.-U. Reiβig et al., Eur. J. Org. Chem., 282 (2009)

3
HO Cl
SmI2 O
NO2 t-BuOH (4 eq.) HN

THF, 0 °C THF, 0 °C CHCl3, rt O

H
87% 60% 65%

J.-P. Dulcère et al., Eur. J. Org. Chem., 2577 (2001)

 Fukuyama Group - Group Meeting Problems
10/16/2013

1 hν, O2*, TPP**

Me CH2Cl2, 0 °C; N
N N
N3 CO2H
Me Me2S
O Me
89%

* H2O would have been contaminated when O2 was bubbled.

** tetraphenylporphyrin: photosensitizer

R. Altundas et al., Org. Lett., 15, 4790 (2013)

2
CO2Me
O MeO2C CO2Me MeO2C CO2Me MeO2C O
BnNH2, CH2Cl2, rt; Ph3P Et3N
tricyclic
O CO2Me
compound
SM, CH2Cl2, rt CH2Cl2, rt EtOH
O reflux CO2Me
85% 85% N
O Bn
78%

I. Yavari and S. Seyfi, Synlett, 23, 1209 (2012)

I. Yavari et al., Helv. Chim. Acta, 93, 1413 (2010)

3 Me

Me OH
AgSbF6 (50 mol%)
B (10 mol%)
O H2O (1.1 eq.) Me
O
Me O
CH2Cl2 (0.1 M), rt
Me O
O
Me 92%
O O
CF3
O B:

CF3
O O
P
O OH
CF3

CF3 D. Z. Wang et al., Org. Lett., 15, 2362 (2013)

 Fukuyama Group - Group Meeting Problems
10/23/2013

1
1) Troc N
N Troc MeSCH2CO2Et*
O OMe O OMe
Me TFA, rt SO2Cl2*, proton sponge® Me
N 95% CH2Cl2, –78 °C; N
NH
N 2) Zn dust Et3N, –78 °C to rt N
Ts Ts
AcOH MeS O
88% 66%
* These reagents are reacted
in advance.

S. J. Danishefsky et al., Angew. Chem. Int. Ed., 46, 1448 (2007)

2
Me
Me Me
O Me
H O O
H O
Me
toluene
O 180 °C
OH
80%

L. Barriault et al., Tetrahedron Lett., 45, 6105 (2004)

3
O
H 1) O3, CH2Cl2, –78 °C; H
Me2S, rt, 94% 3) Ba(OH)2·8H2O
MeO2C CO2Me
O 2) BF3·OEt2, CH2Cl2 MeOH, 0 °C
H –78 °C; O O
allyltrimethylsilane 64% (2 steps)

O. Reiser et al., Org. Lett., 5, 941 (2003)

 Fukuyama Group - Group Meeting Problems
11/13/2013
1
Ph
O cat. (10 mol%)
CHO DABCO O
Ph Ph
+ O
Br CH2Cl2
NH2 rt
(1.5 eq.) N Ph
H
98%
O dr > 25:1
N
97% ee
N N Mes

Cl

cat.
X.-P. Hui et al., Org. Lett., 15, 4750 (2013)

2
1) O
O
Cl
OTroc OTroc
O H H H
OTroc i-Pr2NEt, CH2Cl2 S S SEt
H Me Me
S SEt 10 to 15 °C SEt
Me N + N S
NH 2) P(OEt)3 (2 eq.) O O
S O
O CHCl3, reflux
O O O
A (50%) B (12%)

A. Afonso et al., J. Am. Chem. Soc., 104, 6138 (1982)

A. Yoshida et al., Chem. Pharm. Bull., 31, 768 (1983)

3
CHO 1) mCPBA
CH2Cl2, 40 °C O
2-(trimethylsilyl)ethanol In(OTf)3, MS 4A 95%
O O
OH
toluene, 110 °C CH3CN, 0 to 70 °C 2) TBAF
O THF, rt; O
86% 66% silica gel
50-60%

C.-S. Lee et al., J. Org. Chem., 76, 6534 (2011)

 Fukuyama Group - Group Meeting Problems
11/30/2013

1
TMSN3 1) In (1.0 eq.) O
MeO AgNO3 (10 mol%) NH4Cl (1.0 eq.)
O Zr(NO3)4·5H2O (0.8 eq.) NH
EtOH, reflux
MeO
N CO2Me CH3CN, 110 °C 2) Et3N (5.0 eq.)
Me O
EtOH, reflux N
65% 61% (2 steps) Me

S.-D. Yang et al., Org. Lett., 15, 4158 (2013)

2
Me
Zn (2.0 eq.)
CN BrCH2CO2Et (1.5 eq.) EtO2C
(1.1 eq.)

N dioxane 110 °C N
75 °C;
77% N

S.-g. Lee et al., Org. Lett., 13, 6390 (2011)

3
EtO2C
GaCl3 (10 mol%) EtO2C
EtO2C
nPr
toluene, 60 °C EtO2C
nPr
86%
(E:Z = 10:90) (E:Z = 11:89)

N. Chatani et al., J. Am. Chem. Soc., 124, 10294 (2002)

 Fukuyama Group - Group Meeting Problems
12/10/2013

1
O O3 1) Zn, HCl (gas)
MeOH, –78 °C; Ac2O, 0 °C Me
Me2S, –78 °C to rt; 83%
Me HO Me O
evap.; 2) AcCl, MeOH, 0 °C
HO Me AcOH-PPA, 110 °C 79% OH
62%
PPA = polyphosphoric acid

P. S. Baran et al., Angew. Chem. Int. Ed., 52, 9019 (2013)

2
1) DMF
MeTi(Oi-Pr)3
CyMgBr
THF, rt 1) MeI, Et2O, rt
63% 95%

2) decalin 2) Ag2O, H2O

220 °C 10 torr, 180 °C
93 : 7
82%

A. de Meijere et al., Synlett, 1362 (2002)

3
TMS
Ph Ph
PTSA (5 mol%)
Ph TMS
HO MeCN
80 °C O
51%

R. Chauvin et al., Eur. J. Org. Chem., 5144 (2008)

 Fukuyama Group - Group Meeting Problems
12/21/2013

1) O3, pyridine
Me Me MeOH, –78 °C;
CO2Me
P(OMe)3, –78 to 0 °C
AlMe3 99% HO
NO2
toluene, –76 °C 2) H2 (1 atm), Raney Ni N
MeOH; O OH
59% NaOMe
76%

S. E. Denmark and R. Y. Baiazitov, J. Org. Chem., 71, 593 (2006)

2
1) 1-hexyne MeO
CuI, PdCl2 Cr(CO)5
OMe
PBr3 (2 eq.*) Ph3P, iPr2NEt
Ph n-Bu
DMF (1 eq.*) DMF, rt, 94%
C6H7BrO
O CHCl3 2) Me2NNH2 THF, reflux
0 °C to rt CHCl3, rt
quant. 68% Ph
77%

* theoretical amount
Y. Zhang and J. W. Herndon, Org. Lett., 5, 2043 (2003)
J. W. Herndon and H. Wang, J. Org. Chem., 63, 4564 (1998)

3
1) NaBH4
EtOH, 0 °C OAc
95% 1 torr CO2Me CO2Me

O 2) Ac2O 240 °C xylene, reflux

OAc pyridine, rt
89% 93% OAc
90%

B. M. Trost et al., J. Org. Chem., 43, 4559 (1978)

E. E. Smissman et al., J. Am. Chem. Soc., 84, 1040 (1962)
 Fukuyama Group - Group Meeting Problems
01/11/2013

1
N2H4
O O Me
MeOH, rt;
•
Me OMe
Tl(NO3)3•3H2O (2.0 eq.) CO2Me
Me MeOH, rt

50%
E. C. Taylor et al., J. Org. Chem., 37, 2797 (1972)

2
SO2Ph
Me furfurylamine·HCl, Et3N
CHO MS3A, MeOH; Br2 Me H
H
NaBH4, MeOH AcOH/H2O (1:1) toluene, reflux
SO2Ph N
H
O
91% 77% 70%

D. Y. Gin et al., Org. Lett., 7, 3323 (2005)

3
Me H
O 2-bromopropene Me
t-BuLi air O

O Et2O, –78 °C toluene, reflux CDCl3, 5 °C

OH
99% Me
Me 70% 40% CHO

A. L. Zografos et al., Org. Lett., 15, 152 (2013)

4
NH
N •2HCl
H
O OBn OBn (10 mol%) NaBH4 OBn OBn
+
Ph H DCE, 90 °C MeOH, rt OH
Ph
80% (2 steps)

T. H. Lambert et al., J. Am. Chem. Soc., 134, 18581 (2012)

 Fukuyama Group - Group Meeting Problems
01/16/2013

1
nBu TBSO Me
Me vinyllithium 3SnH
O THF, –78 °C; AIBN (cat.)
Me Me
TBSO O benzene OO
2,3-dibromopropene
–78 °C to rt reflux

79% 81%

J. L. Mascareñas et al., Org. Lett., 3, 1181 (2001)

2
OMe
O O 1) p-TsOH•H2O 1) K2CO3
MeOH-H2O, reflux MeOH, reflux MeO2C
70% 88% HO HN
2) toluene, reflux 2) SmI2 HO
O N 64% THF, rt H
64%
O O
J. D. White et al., Org. Lett., 3, 413 (2001)

3
1) CSA, benzene, 70 °C, 63%
2) PhC(O)CH2OTf
2,6-lutidine, CH2Cl2 LDA
OBn 0 °C to rt, 87% OBn EtNO2 reagent A
S THF;
Et 3) reagent A O
O TBSCl
H O benzene, hν; evap.;
OH Et O
TBAF, THF, –18 °C
74%

E. Vedejs et al., J. Am. Chem. Soc., 111, 8430 (1989)

4
Me3S(O)I* H CO2Me
CO2Me NaH

DMSO, rt O
O O H
O
73%
* theoretically 2 eq.

M. Yamashita et al., Org. Lett., 14, 6048 (2012)

 Fukuyama Group - Group Meeting Problems
01/23/2013

1
Mes N N Mes

:
O O
(10 mol%) Ph
F Ph TMSO
OAr MS4A O OAr
+
O THF, –78 ºC to rt
O
89%

Ar = 4-CH3OC6H4
W. Lupton et al., J. Am. Chem. Soc., 135, 58 (2013)

2
O
1) BrCCl3, DBU LDA
OEt CCl4, hν, 85% 1-acetylcyclopentene TBSO
TBS 2) nBuCu(CN)Li THF, –80 °C;
THF, –80 to –30 °C; SM, –80 to 0 °C
0.06M AcOH in THF nBu
80% 48%

K. Takeda et al., Org. Lett., 1, 677 (1999)

3 O OMe
PdCl2(MeCN)2 (3 mol%)
i-Pr
LiTMP (1.2 eq.) CuI (1.5 mol%), O2
Me O Me
THF THF, rt Me O
–78 °C to rt H
87% i-Pr
OMe 59% O

M. Harmata et al., Org. Lett., 12, 5668 (2010)

4 S
Bn Ts
N N
BnNH3Cl H H H Bn
HCHO aq EDCI N N
Ts
H2O, rt CHCl3, rt NBn
H
100% 67%

J. S. Madalengoitia et al., Org. Lett., 6, 3409 (2004)

 Fukuyama Group - Group Meeting Problems
01/30/2013

1 O
HO Ph
Ph
hν, Pyrex hν, Pyrex
Ph OH
Me
benzene R benzene
O
O 62% O 73%

(R = Me) (R = H)

W. Xia et al., Chem. Commun., 48, 3560 (2012)

2
1) O3, i-PrOH, –2 °C;
NaBH4, NaOH/H2O, rt chloramine-T
90% PhMe3N+Br3- (0.1 eq.) NHTs

2) MePh3PBr+I-, NaH MeCN, rt O

(±)-α-pinene DMSO, 60 °C; E:Z = 1:1
SM, rt to 60 °C 75%
29%

L. Fu-Chu et al., Synth. Commun., 25, 3837 (1995)

S. Chandrasekaran et al., J. Org. Chem., 78, 380 (2013)

3
O
3-butenylamine Tf2O, pyridine toluene
O
THF CH2Cl2 130 °C N
0 °C to rt –78 °C to rt (sealed tube) Tf
63% 75% 96%

A. Padwa et al., Org. Lett., 5, 189 (2003)

4
(1S)-(–)-β-pinene
Hg(NO3)2, CH2Cl2
CN –40 ºC to rt; conc. HCl NH

N NaBH4, NaOH reflux

MeOH HN
H
0 ºC to rt 59%

39%

C. H. Heathcock et al., J. Org. Chem., 58, 564 (1993)

 Fukuyama Group - Group Meeting Problems
02/09/2013

1 OMe
t-BuLi
A
THF, –78 to –20 ºC
OMe O OMe O
MeO MeO OMe
H A hν (350 nm) PDC, celite

THF, –78 to 0 ºC MeOH CH2Cl2, rt Me N

Me NO2
OMe 80% 45% 70% OMe
O

S. J. Danishefsky et al., J. Am. Chem. Soc., 115, 12305 (1993)

2
1) H2, Pd/C
MeOH, –20 °C;
NO2 aq NaNO2, aq HCl NCO
5 °C, 96% Pb(OAc)4
N CO2Et bicyclic
N 2) conc. HCl, rt compound CH Cl , rt NH
2 2
H 86%
CO2Et
58% O

C. D. Campbell and C. W. Rees, J. Chem. Soc. C, 742 (1969)

J. H. Rigby et al., J. Org. Chem. 54, 4019 (1989)

3
1) (Cl3C)2CO, py
THF, reflux
2) Et2NC(S)SNa
NHMe acetone, rt 3) Ph2O, reflux
63% (2 steps) NMe
C14H24N2OS2 89%, 70%
O
3) hv, C6H12, reflux 2 diastereomers 4) PhLi, THF, 0 °C;
74% (32:5) Ph
NaOH aq.
66%

R. S. Grainger et al., J. Org. Chem., 73 8116 (2008)

4
Br
1) Ac2O, DMAP
i-PrO O , n-BuLi CH2Cl2, 0 °C to rt
THF, –78 °C; 69% O

2) Li, NH3 i-PrO

i-PrO O , n-BuLi, –78 °C to rt MeOH, –78 °C to reflux
76% 68%

L. Paquette et al., Org. Lett., 4, 4547 (2002)

 Fukuyama Group - Group Meeting Problems
02/27/2013

1
MeO2C
N N
CO2Me 1) Pb(OAc)4 (2.2 eq.)
MeO2C MeO2C OH
105 ºC, 45 h benzene, reflux, 2 h
BocN S BocN S
2) NaOAc, MeOH
reflux, 24 h

R. B. Woodward et al., J. Am. Chem. Soc., 88, 852 (1966)

2 OTIPS
O OTIPS
Tf2NH (10 mol%)
+ O
CH2Cl2, rt
CHO n-Bu O
71% n-Bu

J. Sun et al., Angew. Chem. Int. Ed., 51, 6209 (2012)

3 Br
O COCl O
H H H H
NH2 Et3N AlMe3 48% aq. HF DBU N
Me Me O
Et2O, 0 °C CH2Cl2, 70 °C MeNO2, rt toluene, reflux
H H
OTIPS 59% (2 steps) 76% 86% 43% O

J. D. White et al., Org. Lett., 15, 882 (2013)

4 O
Me O
O Me
Me PhI(OAc)2 KH O
allyl alcohol A 18-cr-6
Me
OH Me
CH2Cl2, rt THF THF Me
OMe –78 °C reflux
77% O CeCl2
76% 97% H OMe
O A

C.-C. Liao et al., Org. Lett., 5, 4741 (2003)

 Fukuyama Group - Group Meeting Problems
01/08/2014

1
OTBDPS n-BuLi OTBDPS
THF, –78 °C; Me2AlCl
Me Me
O Cl O
CH2Cl2
O SO2Ph MgCl –78 °C to rt O
–78 to –10 °C
TIPS 91% TIPS Me
95%

A. B. Smith, III et al., J. Am. Chem. Soc., 123, 10942 (2001)

2
O CHO
N2 Rh2(OAc)4 HCl aq
O benzene MeOH
rt reflux
O O
87% 85%

A. Padwa et al., J. Org. Chem., 51, 1157 (1986)

3
1) n-BuLi (2.2 eq) O
THF, 0 °C; Hg(OTf)2
CN HCl aq, rt (1 mol%) n-Bu

2) Li CH2Cl2
NHTs
rt N
MeO Ts
OMe 98%
THF, –78 °C
86% (2 steps)

K. Tanino et al., Org. Lett., 14, 1222 (2012)

 Fukuyama Group - Group Meeting Problems
01/15/2014

1
O O
Li
MsCl O H H
i-PrO O
THF, –78 °C; H2SO4 aq. Et3N, DMAP

vinyllithium THF, rt i-PrO

CH2Cl2, rt Cl H
i-PrO O THF, 0 °C to rt
i-PrO O
24% (2 steps) 72%

L. A. Paquette and F. Geng, J. Am. Chem. Soc., 124, 9199 (2002)

2
Cp2Zr(CH3)Cl
t-BuLi, THF CO2Et
Br –78 °C to rt; DBU, toluene, 65 °C;
evap.; I
filt.; CO2Et
N I2, CH2Cl2, 0 °C EtO2C CO2Et
Bn toluene, 85 °C N
70% Bn
53%

S. L. Buchwald et al., J. Am. Chem. Soc., 113, 4685 (1991)

3
Ph

N N
O O
N N

N Br Ph N

O N toluene
reflux
N Br
84%

Y. Cheng et al., J. Org. Chem., 76, 4746 (2011)

 Fukuyama Group - Group Meeting Problems
01/29/2014

1
1) KOt-Bu, Ac2O
OSO2NH2 PhI(OAc)2 (1.1 eq) cat. DMAP
Rh2(esp)2 (2 mol%) Me NHAc
CH2Cl2 OAc
OMe CH2Cl2, 40 °C; –15 °C to rt;
C14H19O4NS
NaBH4 2) KOAc
MeOH, rt DMF, 40 °C
Me
3) HCl in Et2O
85% C6H5Cl, 75 °C
68% (3 steps)

J. S. Panek et al., Org. Lett., 16, 74 (2014)

s-BuLi (1.4 eq)

(–)-sparteine (1.4 eq) BF3·OEt2, CH2Cl2, rt; c-Hex O c-Hex
O Et2O, –78 °C; B, –78 °C;
C13H25O2B
EtO NiPr2 A (1.7 eq) BF3·Et2O, –78 °C to rt n-Bu Me
–78 °C to rt; OH
evap.; 57%, dr = 99:1

O
A: B: CHO
B
n-Bu O

V. K. Aggarwal et al., Tetrahedron Lett., 54, 49 (2013)

3
O O O O
Li, MeOH DDQ (2.0 eq)
N N O
NH3, –35 °C CHCl3, rt benzene, rt
H H
O
75% 74% 90%

˘
H. Çadvar and N. Saraçoglu,Tetrahedron, 61, 2401 (2005)
 Fukuyama Group - Group Meeting Problems
02/08/2014

1 cat.
Me Me
S

HO OH
t-Bu t-Bu MeO
OMe NO2 O O
15 kbar Et3N N
+
CH2Cl2 CHCl3 Ph
Ph 0 ºC H H
rt Ph
1 eq. 2.05 eq.
64% 74%
(15:9:1)

H. W. Scheeren et al., Eur. J. Org. Chem., 4397 (2004)

2
N Me
NsHN
Et2 Me O
Si TBSOTf (1.0 eq.)
O O Grubbs 2nd 2,6-lutidine PPh3, DEAD O
TMSO Ph toluene, 90 °C; CH2Cl2, –78 °C; THF, 0 °C to rt; O 6
Me Me
TBAF, AcOH triphosgene, rt; CF3CH2OH-H2O Me
Me rt TBAF, 0 °C to rt 0 °C Ph

Me 74% 67% 71% (6S:6R = 3:1) Me

M. Movassaghi et al., Angew. Chem. Int. Ed., 45, 5859 (2006)

3
n-BuLi
THF, –78 °C;
TESCl 1) BzCl
Et3N O
–78 °C to rt; NH3
HO Ph N
s-BuLi, –78 °C; MeOH, 40 °C 2) toluene H
MsCl 110 °C;
–78 °C to rt 27% H2O
81% (2 steps)
65%

S. J. Danishefsky et al., J. Am. Chem. Soc., 126, 6347 (2004)

 Fukuyama Group - Group Meeting Problems
02/19/2014

1
Ph
Ph O [Rh2(esp)2]
(5 mol%)

toluene, 130 °C N
N3
87% O

T. G. Driver et al., Angew. Chem. Int. Ed., 53, 785 (2014)

2
O OMe
CHO NHOH H
N
OMe
+ + O
MW
t-Bu O 75% t-Bu

S. Muthusubramanian et al., Tetrahedron Lett., 47, 4221 (2006)

3
I I
O O OH•NEt3

I I
Cl CO2H•NEt3

Cl Cl
Cl
O2, hν Ph3P CO2Bn (1.03 eq) O
Ph BnO2C Ph
CH2Cl2 CH2Cl2, rt
5-10 °C
100%
30%

D. K. Taylor et al., J. Org. Chem., 65, 5531 (2000)

 Fukuyama Group - Group Meeting Problems
03/01/2014

1
OTIPS
O
OTIPS HNTf2 (0.1 eq)
O
O n-Bu CH2Cl2, rt
O
71% n-Bu

J. Sun et al., Angew. Chem. Int. Ed., 51, 6209 (2012)

2
N
O n-BuLi, THF, –78 °C; N
OMe C4F9SO2N3; MeO2C H
+
HN
AcOH, –78 to 25 °C Me N
Ph
Me Me 95% Me Ph
trans/cis = 15:1

U. Jahn et al., Org. Lett., 16, 1088 (2014)

3
Oi-Pr
Oi-Pr PtCl2
(10 mol%)
O + On-Bu
toluene
rt
O H
91%

N. Iwasawa et al., Org. Lett., 6, 605 (2004)

 Fukuyama Group - Group Meeting Problems
03/08/2014

1
1) H2O2 aq.
Et2Zn (excess) NaHCO3 Ph OH HO Ph
toluene, rt; MeOH-THF Ph Ph
Ligand (5 mol%), rt; 0 °C to reflux n-Bu OH N OH N
TMS
O HO
2) K2CO3, MeOH
rt, 83% H
Si n-Bu I
Me Me , 15 °C; > 96% de, 90% ee Me
THF, 45 °C; Ligand
I2, 0 °C to rt

I. Marek et al., Angew. Chem. Int. Ed., 52, 13717 (2013)

2
OH Me 1) Pb(OAc)4 H O
AcOH K2CO3 NaIO4, HCl aq.

2) xylene EtOH THF

HO2C
reflux Me
96% 67%
22% (2 steps)

P. Yates and T. S. Maras, Can. J. Chem., 66, 1 (1988)

3 Br
(1.2 eq)
In, THF-H2O, rt;
evap.;
4-methoxybenzaldehyde
TMSBr, CH2Cl2, 0 °C;
CHO evap.; O

HO NaBH4, InBr3 OMe

THF, rt
HO
58%

T.-P. Loh et al., Tetrahedron Lett., 50, 4368 (2009)

 Fukuyama Group - Group Meeting Problems
04/05/2014

1
Me
OTBDPS 1) Rh2(OAc)4 LDA, THF OTBDPS
O benzene, reflux –78 °C; Me
C30H38O4Si O
O OH 2) (Ph3P)3RhCl TMSCl CO2H
N2 Ph3P, TMSCHN2 –78 to 0 °C
O i-PrOH
dioxane, 60 °C dr = >100:1
60% (2 steps)
S. Nakamura et al., Org. Lett., 16, 2054 (2014)

2
1) PhI(OAc)2 (5 eq)
Br2 (8 eq) 1) SmI2 O
O Me hν, CH2Cl2, –30 °C; DMPU/THF (1:9) Me O
OH Me H O TMSCl, imidazole 23 °C; TBCHD TMS O
0 °C, 57% –78 °C
O O
O H H 2) DBU, LiCl 2) LiBr, Li2CO3 H
OHCN O O
THF, 23 °C, 85% DMF, 60 °C OHCN O
H 65% (2 steps)
H O
Br Br

Br Br
TBCHD

P. S. Baran et al., J. Am. Chem. Soc., 133, 8014 (2011)

3
n-BuLi, THF; O
TsN3 Rh2(OAc)4 (5 mol%)

–78 °C to rt toluene, reflux i-Pr

i-Pr O O
H H
81% 83%

A. Boyer et al., Org. Lett., 16, 1660 (2014)

 Fukuyama Group - Group Meeting Problems
04/12/2014

1
1) PhI(OAc)2 O
allyl alcohol O
CH2Cl2, rt
Me OMe 77% KH, 18-crown-6
Me *1
2) A THF, reflux
OH THF, –78 °C
76% 97% O
H OMe
O
A= O O *1 stereochemistry
CeCl2 not determined

C.-C. Liao et al., Org. Lett., 5, 4741 (2003)

2
1) NaHCO3 3) n-BuLi, CuI
I2 TMSCl, THF
acetone-H2O –78 °C to rt n-Bu
0 °C, 87% 92%

BocHN O N OMe 4) vinyllithium

O 2) Ag2O, MeI Boc Me N
THF, –78 °C Bn
CH2Cl2, rt
5) benzylamine (excess)
99% p-TsOH (cat.)
µW, 150 °C
42% (2 steps)

A. Padwa et al., Org. Lett., 11, 1233 (2009)

Ti(Oi-Pr)4 (cat*) 1) MsCl, Et3N

TBSO CO2Et EtMgBr (2 eq.*) Et2O, 0 °C TBSO
OTBS THF, 10 °C 2) MgBr2·OEt2 OTBS
Br
CH2Cl2, reflux
73% (3 steps)
*theoretical amount

J. Mulzer et al., Org. Lett., 10, 4701 (2008)

 Fukuyama Group - Group Meeting Problems
04/16/2014

Ph
OH AgOTf N
N (10 mol%)
+
DMSO, 100 °C O
Ph Ph
76% Ph

J. Wu et al., Chem. Commun., 50, 4188 (2014)

O O Ph O O
Rh2(OAc)4 Br
O O
O Ph
N2 benzene xylene
reflux 145 °C (sealed tube)
Br O
36% (2 steps)

A. Padwa et al., Org. Lett., 5, 3337 (2003)

1) i-PrMgCl·LiCl
I DMDO, ZnCl2, furan THF, –78 °C
MS 4Å 63% O
Ts
N N
• CH2Cl2, –78 °C to rt 2) t-BuOK, CS2
THF, 0 °C to rt Ts
70% 82%

B. J. Haugen et al., Org. Lett., 16, 2180 (2014)

 Fukuyama Group - Group Meeting Problems
05/07/2014

1
N2
MeO OMe
O
O O
5-bromo-1-pentene Cu N2H4 CO2Me
N K N
DMF 140 °C MeOH
rt to 60 °C reflux O
O 70% (2 steps)
quant.

S. Danishefsky and J. Dynak, J. Org. Chem., 39, 1979 (1984)

2
O
HO
Br O H H
MeO
O Mg, 1,2-dibromoethane p-TsOH•H2O O
THF, rt acetone
n-Bu reflux
92% n-Bu
73%

S. Kim et al., J. Org. Chem., 65, 4864 (2000)

3
O
PhNHNH2
OMe A
MeO
EtOH
O rt

malononitrile NH
O Et3N Cl O
Cl EtOH, rt; CO2Me
NC
O
A, rt N
N
H H2N O N
72 % Ph

L. H. Choudhury et al., Tetrahedron Lett., 54, 5434 (2013)

 Fukuyama Group - Group Meeting Problems
05/24/2014

1
LDA, THF, 0 °C;
O O
MeO2C
MeS
O H MeO2C Cl DMTSF
O H
TMS SMe –78 °C; MS 4A MeCN, –40 °C;
N
Ac2O, –78 °C to rt CH2Cl2, rt Et3N O
MeS N
80% 85% 80%
dr = 4:1 dr = 1:1

DMTSF
S
S
BF4

J. D. Jinn and A. Padwa, Org. Lett., 4, 1515 (2002)

2 1) KI
LiHMDS (1.2 eq) AcOH
O
THF, –78 °C; 100 °C O
aldehyde; 99%
N
C17H16N2O2 N
N Ac2O 2) Ac2O-pyridine
–78 °C to rt; 100 °C
OMe DBU 3) microwaves
rt to 100 °C CHO toluene
87% (2 steps)
46%

aldehyde

J. R. Scheerer et al., Org. Lett., 16, 904 (2014)

3
O O
1) mCPBA mCPBA
O MeOH, rt AcOH O
H HH
2) xylene, reflux DCE
82% (2 steps) 45 °C HO
N H
H O N H
76%

Z. Yang et al., Angew. Chem. Int. Ed., 52, 620 (2013)

 Fukuyama Group - Group Meeting Problems
06/04/2014

1
O OH O
Hg lamp H
MeO
(medium pressure) O
N
N N
MeCN MeO
O O O

76% 14%

K. I. Booker-Milburn et al., Org. Lett., 6, 1481 (2004)

2
O H
hν MeLi (2.1 eq) O
O
O
aq. MeOH Et2O
Me OAc 10 to 55 °C Me OH H
–78 °C to reflux
60% 63%

F. G. West et al., Org. Lett., 10, 3733 (2008)

3
1) CuCl, Ag2CO3
phenanthroline 3) norbornadiene
KOt-Bu, TMSCF3 toluene, 70 ºC H O
DMF, 40 ºC 79%
C11H23
2) Co2(CO)8 4) DBU, H2O
hexanes, rt CH3NO2, reflux H
61% C11H23
87% (2 steps)

A. Riera et al., Angew. Chem. Int. Ed., 52, 5355 (2013)

 Fukuyama Group - Group Meeting Problems
06/10/2014

1
Ph R
Ph
10% KOH aq., rt; R

4 M HCl aq., rt O
O
NO2 83%
R = 2-pyridyl

H. E. Zimmerman et al., Helv. Chim. Acta, 84, 1342 (2001)

2
NH2 CHO 1) MeCN, rt;
N
TFAA, 0 °C;
OHC NaBH3CN, rt, 66% O
+ O
CO2i-Pr 2) NaOH, EtOH-H2O
MeO N 75 °C, 88% N H
MeO
OMe Me TMS 3) K3Fe(CN)6, NaHCO3
OMe Me
t-BuOH-H2O, rt, 92%

E. J. Corey et al., J. Am. Chem. Soc., 121, 6771 (1999)

3
O TBSOTf (2.1 eq) O
2,4,6-collidine (4.2 eq)
Me OMe Me
( )14 N ( )14 N OTBS
CH2Cl2, rt
Me Me
61%

J. A. Murry et al., Tetrahedron Lett., 34, 6215 (1993)

 Fukuyama Group - Group Meeting Problems
06/18/2014

1
Ph Me
PhIO, Tf2NH N
O
MeCN, rt
Ph
Me Me
70%

A. Saito et al., Org. Lett., 15, 2672 (2013)

2
O CO2Me
O Ph Ph CO2Me
N DMAD N
H
toluene, reflux Ph
H
O Ph 60% O
dr = 6.5 : 1

O. Tsuge et al., Chem. Lett., 797 (1984)

3
Me
Me Me BH3•SMe2 Me
Me CH2Cl2, –78 °C to rt; n-Bu3P, DIAD
Me N
I2, NaOMe THF, 0 °C
NH2 MeOH, rt;
H2O2 44% (2 steps) Me Me
dr = 76 : 1

DIAD = diisopropyl azodicarboxylate

R. A. Shenvi et al., J. Am. Chem. Soc., 134, 2012 (2012)

 Fukuyama Group - Group Meeting Problems
07/02/2014

1
Cl
Si
KF, KHCO3 O N O
O Al2O3
NO2 imidazole2 H2O2 aq. n-Bu
n-Bu
H +
CO2Et 0 °C MeCN, rt THF-MeOH R
Br HO OH
0 °C
76% 97% (R = CO2Et)
cis/trans = 1:9 cis/trans = 1:5 >72%
(from cis isomer)

G. Rosini et al., J. Org. Chem., 56, 6258 (1991)

G. Rosini et al., J. Am. Chem. Soc., 118, 9446 (1996)

2
O Cl n-Bu
n-Bu
OH I O
K2CO3, ICl
n-Bu O
n-Bu MeCN, rt

92% I
OMe OMe

Y. Liang et al., Org. Lett., 16, 2236 (2014)

3
H NH
N3 TfOH
+ N toluene N H
Ts 0 °C to rt
Ts
88%

H. Zhai et al., Org. Lett., 13, 6331 (2011)

 Fukuyama Group - Group Meeting Problems
07/16/2014

1
NC CO2Et
O 1) (COCl)2 N
CH2Cl2, reflux HO
N N COMU
O 2) KPF6 MeCN, rt
CH2Cl2-H2O, rt
89%
84% (2 steps)

COMU Me Me H
Me Me iPr2NEt N CO2Me
+ CbzHN
CbzHN CO2H H2N CO2Me DMF, rt O
99%

A. El-Faham et al., Chem. Eur. J., 15, 9404 (2009)

2
OH TMS MsCl H O
NaOCl aq. pyridine
N N
CH2Cl2 CH2Cl2
0 °C to rt 0 °C TMS

82% 48%

T. Ishikawa et al., Angew. Chem. Int. Ed., 41, 1586 (2002)

3
S
S
Ph3P (cat.) PPh2
PPh2 CO2Et HN
N + BocO
toluene
MeO OH 110 °C
MeO O CO2Et
72%
trans/cis = >99:1

R. Chen et al., Org. Lett., 12, 3768 (2010)

 Fukuyama Group - Group Meeting Problems
08/06/2014

1
O
(2 eq.) MOMO
N •
Li Li O
HO
Br Br THF, –78 °C; THF, –78 °C;
C10H16BrNO2
O HCl, EtOH
Br Br
0 °C
H
75%
THF, reflux

71-73%

M. A. Tius et al., Org. Lett., 4, 3363 (2002)

1) NaBH4
MeOH
NTs Rh2(piv)4 (cat.) rt
N N
N toluene 2) I2, K2CO3 Ts
N
reflux NTs CH2Cl2 HO N
Ts rt Ts
86%
63% (2 steps)

M. Shi et al., Angew. Chem. Int. Ed., 53, 6645 (2014)

3
Sc(OTf)3 (5 mol%) N
Boc microwave
NH2
O O N H MeCN, rt to 125 °C O
+ +
H CO2Me 82% HN
O
H

O. Reiser et al., Angew. Chem. Int. Ed., 51, 4722 (2012)

 Fukuyama Group - Group Meeting Problems
08/23/2014

n
1) TMSCHN2 Boc
LHMDS
Grubbs 2nd THF-HMPA CH2Cl2-MeOH N
OAc (5 mol%) –78 °C; rt, 91% O
diene Boc
Ph C17H20O2
CH2Cl2 TBSCl, rt 2) BocNHOH* N
40 °C Pr4NIO4*, CH2Cl2 HO
68% 0 °C, 76% Ph CO2Me
64% dr = 1.7:1
(*theoretically 2 eq)

S. T. Diver et al., J. Am. Chem. Soc., 128, 15632 (2006)

O N NH
N AcOH

NH2 55 °C
N O
H
80% N

V. A. Mamedov et al., Tetrahedron Lett., 55, 4319 (2014)

3
O O O Me
Pd(PPh3)4
EtO Me i-Pr2NEt EtO
+ Ph Br O
DMF, 90 °C Ph

t-Bu
45% t-Bu

J. Wang et al., J. Am. Chem. Soc., 135, 13502 (2013)

 Fukuyama Group - Group Meeting Problems
09/10/2014

1
TBSO OTBS CO Me
2
CO2Me
AgOTf
O NTr
MeCN, 70 °C; N NTr
N BnMe3NCN, rt
O
I 91%

H. Kohn et al., J. Am. Chem. Soc., 125, 15796 (2003)

2
1) TIPSOTf
i-Pr2NEt
O Et2O-hexane
N2 0 °C to rt TMSCHN2
Ketene O
2) hν (300 nm) CH2Cl2, rt;
benzene, rt aq HCl

70% (2 steps) 69%

R. L. Danheiser et al., Org. Lett., 4, 2465 (2002)

3
NH2CO2Me
HC(OEt)3, Zn, Cu
ZnCl2, TMSCl
Mes Mes NHCO2Me
Et2O, rt

83%, dr = 7:1

W. B. Motherwell et al., Angew. Chem. Int. Ed., 52, 10060 (2013)

 Fukuyama Group - Group Meeting Problems
09/17/2014

1
TMS Ti(Oi-Pr)4, n-BuLi Me Ph Me Ph
TMS TMS
toluene, –78 to 50 °C;
OH OH
A, –78 °C to rt; Ph Ph
Ph MeOH, –78 °C H
Me
64% 15%
Ph dr = 10:1
A: Me
OPh
OLi

G. C. Micalizio et al., J. Am. Chem. Soc., 136, 8209 (2014)

2
O
BocHN
OH
O
O O
Ph
N BocHN
+ O Ph
N3 O
THF-H2O toluene
O rt 80 °C Ph
PPh2
80% 50%

E. L. Myers and R. T. Raines, Angew. Chem. Int. Ed., 48, 2359 (2009)

3
allylamine,tert-butylisocyanide AcHN
CHO CO2Et
AcOH, MeOH, rt;
MeO MeO
CO2Et
diethyl malonate, Mn(OAc)3·2H2O (4.5 eq),
MeO AcOH, 90 °C MeO

59%

L. E. Kaim et al., Org. Lett., 9, 4171 (2007)

 Fukuyama Group - Group Meeting Problems
09/24/2014

1
Ts
Ts TfOH/CH2Cl2 H N
N (0.8:1)

0 °C
H
90%

S. Thibaudeau, G. Evano et al., J. Am. Chem. Soc., 136, 12528 (2014)

2
OMe
3-butyn-1-ol CO2Me
O
Me Pb(OAc)4
H
N oxadiazoline
Me N CO2Me CH2Cl2 toluene
0 °C reflux O Me
Me
37% 74%

K. Kassam and J. Warkentin, J. Org. Chem., 59, 5071 (1994)

3
(p-tol)3PAuNTf2
(10 mol%)

1,2-DCE, 50 °C Ph
Ph
72%

M. R. Gagne et al., Angew. Chem. Int. Ed., 53, 7904 (2014)

 Fukuyama Group - Group Meeting Problems
10/01/2014

1
cat. CuBr•SMe2
NO2 H2O (6.0 eq) NO2
Et3N (1.2 eq)
TsN3 O
N MeCN
O Ph N
rt
Ph NHTs
71%

M. Terada et al., Org. Lett., 16, 5184 (2014)

2
t-Bu +
AcO TBSO t-Bu SbF6–
P Au NCMe
Me OTBS
Au cat. (2 mol%) H
+
CH2Cl2, rt Me
TBSO OTBS Au cat.
OAc
52%

A. M. Echavarren et al., Angew. Chem. In. Ed., 52, 6396 (2013)

3
Ph
Ph
N
N
N N Li

OBn
THF, 0 °C

N 65%
N Ph

S. Kim et al., J. Am. Chem. Soc., 121, 5330 (1999)

 Fukuyama Group - Group Meeting Problems
10/15/2014
1
O
1) Ti(Oi-Pr)4 (cat), EtMgBr (3 eq)
O THF, 15 °C, 70%

O 2) O Na2SO4, Al(OTf)3
O
CH2Cl2, –10 °C
H
TiCl4, 55%

K. P. C. Minbiole et al., Org. Lett., 7, 515 (2005)

2
Ts
N TFA O
CH2Cl2, rt;
evaporation; H
1,4-dioxane
HO cyclopropane H
TBAF 70 °C H
THF, 0 °C N
OH 88% N Ts
91% Ts
NHTs

Y. Hamada et al., Chem. Commun., 50, 12775 (2014)

3
O
OH 1) Ishikawa's rgt (PPDA) OH F CF3 DIBAL NHBn
CHCl3, rt, 74% (2.2 eq) O CF3
Me Ts Me CONHBn
2) BnNH2 THF
2-hydroxypyridine Ts reflux
THF, rt, 99% Ts
76%

F
Ishikawa's rgt : NEt2
(PPDA) F3C
F F

K. Ogura et al., Org. Lett., 7, 589 (2005)

 Fukuyama Group - Group Meeting Problems
11/08/2014
1
Me O
Br 1) t-BuOK, DMSO 1) m-CPBA, NaHCO3
30 to 40 °C, 85% CH2Cl2, 0 °C, 85% Br
OH 2) aq. HBr, THF 2) ZnBr2, benzene Me
Me 0 °C, 85% reflux, 80%
Ph Ph

W.-D. Z. Li et al., Org. Lett., 7, 3107 (2005)

2
Ph Ph
MeO2C RhCl(IPr)(cod) (5 mol%) O
MeO2C AgSbF6 (5 mol%)
MeO2C H
O
DCE, 75 °C MeO2C
H
Ph 94% Ph

J. Zhang et al., J. Am. Chem. Soc., 133, 7304 (2011)

3
Ph
HN O
Na (4.0 eq)
TMSCl (4.0 eq) CN
CO2Me
MeO2C N CN
toluene, reflux MeOH, rt
78% 75% Ph

Ph Li O Ph
(2.5 eq) AgNO3

THF EtOH N
–78 °C 50 °C H Bn

58% 93%

J. J. Bloomfield and J. M. Nelke, Org. Synth., 57, 1 (1977)

L. E. Overman et al., J. Org. Chem., 50, 2403 (1985)
 Fukuyama Group - Group Meeting Problems
11/15/2014

1
Me
Me
O CO2Et DBU
Me Me
N Et2O, rt N CO2Et
O
H O
84%

T. Gilchrist et al., J. Chem. Soc. Perkin Trans. 1, 2505 (1987)

2
1) HS PPh2•BH3 O
N3 HATU, i-Pr2NEt O3, CH2Cl2, –78 °C;
CH2Cl2, rt, 91% Ph3P, rt; N
lactam
NO2 2) DABCO, THF-H2O H2, PtO2, rt; H
CO2H reflux, quant. HCl, MeOH, rt
N
H

J.-P. Zhu et al., J. Am. Chem. Soc., 136, 15102 (2014)

3
H Hg vapor lamp H
TFA, TPP, air O
CH2Cl2, –10 °C;
O
O
H H aq. NaHCO3 HO H
EtO O
55% after crystallization
O O O

J. Turconi et al., Org. Proc. Res. Dev., 18, 417 (2014)

 Fukuyama Group - Group Meeting Problems
11/22/2014

1
N Cl
N N Mes
O (20 mol%) Ph
O
OH + DBU (50 mol%)
Ph
MeO2C Ph MeO2C Ph
Me Me
CH2Cl2, 40 °C

60%, dr= 6:1

J. W. Bode et al., J. Am. Chem. Soc., 131, 8714 (2009)

2
CHO 1) MeNHOH·HCl, NaOAc NMe
CH2Cl2, rt, 72%
O
2) KOH, MeOH, rt
Ph Ph
88%

W. Eberbach et al., Eur. J. Org. Chem., 2715 (2005)

3
KHMDS (2.5 eq) TMSCl (2 eq)w
Br2 (3.6 eq) n-BuLi (2.1 eq)w
C15H23NO3SSi
N O toluene-THF, –78 °C THF, –78 °C
Ts
53% 73%

Ph
Ph
O
Ph
KHMDS Ph
Ph
Tf2O CsF Ph
toluene-Et2O, –78 °C CH3CN, rt
N Ph
Ts
81% 83% Ph

R. L. Danheiser et al., J. Am. Chem. Soc., 136, 15489 (2014)

 Fukuyama Group - Group Meeting Problems
12/03/2014

1
Br O2
PdCl2 (10 mol%)
K2CO3 O O
O O O CuCl2
S
S Ph tol
Ph tol acetone THF-MeOH, rt; N
H
reflux NH4OAc

86% 86%

Y.-J. Lu et al., Org. Lett., 16, 6252 (2014)

2
NC O
O CO2Me
MeO2C
NH2 CN EtOH
OH NH2
Ph
Ph CN reflux MeO2C Ph
OH CO2Me N
76% Ph

Z.-B. Huang and D.-Q. Shi et al., Org. Lett., 15, 2542 (2013)

3
O
O R (10 mol%)
R O
O 1) O3 O O
O SiEt3 acetone, rt, 77%
S OEt Ph OEt
Ph
EtOAc, reflux 2) Cs2CO3
S 18-crown-6 SiEt3
92% 1,4-dibromobutane
MeCN, reflux
(R = C11H23)
65%, dr= 2.1:1

S. Zard et al., Org. Lett., 16, 6180 (2014)

 Fukuyama Group - Group Meeting Problems
12/13/2014

1
PhI(OAc)2 (3 eq.)
O O Et
conc. H2SO4
Et N
Ph N Ph Et
EtOAc, reflux
Et O
90%

Y. Du and K. Zhao et al., Org. Lett., 16, 5772 (2014)

2
O
O O
CO2Et
N c-Hex
+ N N +
CHO C N c-Hex
EtO2C MeCN, rt
O O N NHCO2Et
77% CO2Et

J. Stephanidou-Stephanatou and C. Tsoleridis et al., Tetrahedron Lett., 55, 5601 (2014)

3
Ph
TsN3
NTs
CuI (10 mol%) LHMDS
Ph N NH
MeCN, rt THF Cy
–78 °C to rt;
Cy N C N Cy 89% H2O

99%

X. Xu et al., Org. Lett., 9, 1585 (2007)

Z. Xi et al., J. Am. Chem. Soc., 134, 2926 (2012)
 Fukuyama Group - Group Meeting Problems
01/07/2015

1
1) MeI, THF, 0 °C;
Fe(CO)3 A, THF-DMF ethylene (1 atm) H
0 to 80 °C, 50% Grubbs 2nd (5 mol%)

2) Me3NO, acetone benzene, 50 °C to reflux

NMe2 H
56 °C, 64% H
74% O

ONa
A
M. L. Snapper et al., J. Am. Chem. Soc., 122, 8071 (2000)

2
S S
n-BuLi Ph
THF, hexane Ph S
–78 °C; InCl3 (10 mol%) S
Ph
C21H16O
benzophenone DCE
–78 °C to rt 80 °C Ph
Ph
98% 87%

H. Tanimoto et al., Org. Lett., 15, 5222 (2013)

S. Muthusamy et al., Chem. Commun., 51, 707 (2015)

3
Ph Me Me
O O
IPrAuOTf (5 mol%) m-CPBA O

MeCN, rt DCM, 0 °C Ph
N
N
85% 81%
O O

G. Zhou et al., Chem. Comm., 46, 6593 (2010)

 Fukuyama Group - Group Meeting Problems
01/14/2015

1
1) (Cl3C)2CO, Ph3P
O
OH CH2Cl2-Et2O, 0 °C 1) K2CO3, MeOH
93% rt, 94% H
O C19H27ClO3
O 2) hν (Hg lamp) 2) LiAlH4, Et2O
CH3CN-acetone rt, 88% H
O 0 °C, 60% 3) DBU, 200 °C OH
H 77%
C19H28O4

J. D. Winkler et al., J. Am. Chem. Soc., 124, 9726 (2002)

2
N (1.0 eq)
Boc
lauroyl peroxide (5 mol%) 2-methylallylamine (2.0 eq) NHBoc
O
2,6-lutidine p-TsOH (0.5 eq)
S OEt
t-Bu EtOAc, reflux 1,4-dioxane, reflux t-Bu N
S
68% (2 steps)

S. Z. Zard et al., Org. Lett., 16, 1992 (2014)

3
HPF6
O POCl3 (1 eq.) NaOH Cl
Cl Me2N NMe2 PF6
Cl DMF H2O, rt
70 °C;
vinamidinium salt
77%

I. W. Davies et al., J. Org. Chem., 65, 8415 (2000)

J. Taylor et al., Org. Synth., 80, 200 (2003)
 Fukuyama Group - Group Meeting Problems
01/21/2015

1
TESO Pd(PPh3)4 (10 mol%)
CO (800 psi) TESO
O i-Pr2NEt
R O
R O
PhCN, 70 to 110 °C
H O
TfO 56%
OH

R = Me
4

M. M. Bio and J. L. Leighton, Org. Lett., 2, 2905 (2000)

2
O
PtCl2 (10 mol%)
*CO (1 atm) Me
OH
Ph O toluene, 60 °C; Me
OAc silica gel
Ph O O
78%

* Ligand

X. She et al., J. Am. Chem. Soc., 132, 1788 (2010)

3
1) (COCl)2, DMF
CH2Cl2, 22 °C;
AlCl3, –10 ºC;
CH2=CH2, –10 °C
95-100% 1 M HCl NH2
CO2H

Br 2) 50% aq NH2OH AcOH Br

MeOH, 22 °C 75 °C
75-83%
60-78%
W. Li et al., Org. Proc. Res. Dev., 18, 1696 (2014)
 Fukuyama Group - Group Meeting Problems
01/28/2015

1
OH
O 1) DMF, 250 °C (µW)

2) NaBH4, EtOH, 0 °C
50% (2 steps)

D. P. Curran et al., J. Am. Chem. Soc., 137, 322 (2015)

2
OMe HO
HO 1) hν, hexanes, 20 °C, 90%
2) LiAlH4, THF, 0 °C, 89% HO OH
MeO H
O
3) PhI(OAc)2 OMe
CF3CH2OH-acetone, –40 °C; O
O HO
NO2 THF-H2O, –40 °C, 40%
(±)-tanegool

J.-P. Lumb et al., Angew. Chem. Int. Ed., 54, 2204 (2015)
C. Kibayashi et al., J. Am. Chem. Soc., 126, 16553 (2004)

3
OTBS
CO2Me

N2
O Rh2(pfb)4 (2 mol%) MeO
N
HN O O
MS4A, CH2Cl2
0 °C to rt;
OMe CuPF6; silica gel MeO2C

92%

pfb = perfluorobutyrate

M. P. Doyle et al., Org. Lett., 14, 800 (2012)

 Fukuyama Group - Group Meeting Problems
02/14/2015
solution: Hattori
chair: Toma

1
Rh2(S-DOSP)4* MeO2C OH
Me OH N2 heptane, 0 to 80 °C;

Me Me Ph CO2Me Sc(OTf)3
Ph
95%, 82% ee

H O Rh
N
*S-DOSP= O Rh
S O
O
C12H25

H. M. L. Davies et al., Chem. Sci., 2, 2378 (2011)

2
EtO O
O O O O HO
1) MgCl2, pyridine 1) BF3•OEt2, CH2Cl2
O O AcCl, CH2Cl2, 0 °C –78 °C, 60%

2) Pd(PPh3)4, THF, rt; 2) K2CO3, EtOH O

silica gel rt, 89%
66% (2 steps) H
O HO
H

T. N. Barrett and A. G. M. Barrett, J. Am. Chem. Soc., 136, 17013 (2014)

3
1) Rh2(OAc)4
(0.2 mol%) TsN Ph
O
O 20 ºC, 78-91% MgI2
N2 + cyclopropane NHTs NAr
EtO Br 2) NaH, EtOH THF, reflux
Et2O, reflux, 71% Ph
3) ArNH2, AlMe3 72%
DCE, reflux Ar =
N

M. Lautens et al., Org. Synth., 85, 172 (2008)

M. Lautens et al., J. Am. Chem. Soc., 125, 4028 (2003)
 Fukuyama Group - Group Meeting Problems
02/21/2015

1
CO2Ph O
O 1) LiAlH4
K2CO3 THF, –50 °C *TBAF
SO2Ph
acetone, reflux 2) DMP (2 eq.) THF, rt Me
CH2Cl2, rt
82% 60% (2 steps) 95% SO2Ph

*containing water

S. D. Lepore et al., J. Org. Chem., 79, 9402 (2014)

2
t-BuLi (4 eq) BnN3
N
I Et2O, –78 °C; La(OTf)3 (10 mol%)
N t-Bu NBn
I t-BuCN (2.4 eq), reflux; t-Bu t-Bu benzene, 80 °C H N
(t-BuO)2, rt N H
76%
t-Bu
66%

Z. Xi et al., Angew. Chem. Int. Ed., 52, 3485 (2012)

3
OMs Me
1) KOt-Am, HOt-Am H O OH
Me
102 °C, 74% hν, TFA H
O
2) OsO4, NMO pentane
HO acetone-H2O, 72% EtO
(dr= 9:1) 82%
OEt OMe MeO

E. M. Carreira et al., Angew. Chem. Int. Ed., 40, 2694 (2001)

 Fukuyama Group - Group Meeting Problems
02/28/2015

t-Bu
Ph SbF6
Ph t-Bu P Au NCMe
Au cat.
+
D DCE, 120 °C

72% D Au cat.

A. M. Echavarren et al., Angew. Chem. Int. Ed., 53, 14022 (2014)

2
Me HO Me
1) A, Eu(FOD)3 (10 mol%)
toluene, 80 °C, 84% LiDBB
Me
Me THF, –78 to 10 °C
2) hν, Corex filter, 79% H
Me
O Me 57% Me

Me
A
V. H. Rawal et al., Org. Lett., 2, 2711 (2000)

3 O
O O
S
HN
S Ph3P N S N
Ph3P
OH , BnOH NHCbz
O
Me CO2Me CH2Cl2, rt toluene Me CO2Me
reflux
52%, 92% ee
59%, 90% ee

M. E. Wood et al., Tetrahedron, 61, 2141 (2008)

 Fukuyama Group - Group Meeting Problems
03/04/2015

1 H
1) N O

Me
aq. HClO4, dioxane
O O 105 °C (sealed tube) Pb(OAc)4 H
N O
NH2
2) Boc2O, Et3N CHCl3, rt
Me THF, 60 °C N Boc
65% (2 steps) 84%

R. Sarpong et al., J. Am. Chem. Soc., 132, 5926 (2010)

2
I

Pd(PPh3)4 (cat.) O Me
OBn
Me CO (200 psi)
HO OBn CO2 (200 psi)
O O
O Et3N, 100 °C
O O
79%

K. C. Nicolaou et al., J. Am. Chem. Soc., 130, 11114 (2008)

3
t-Bu t-Bu
Si
Me
Me
O AgOTs (10 mol%) HO CO2H
toluene, –25 °C;
O n-Bu Me
Me Me
HF•pyridine, rt
O Me n-Bu
77%, 97% ee
97% ee

K. A. Woerpel et al., Org. Lett., 9, 4651 (2007)

 Fukuyama Group - Group Meeting Problems
04/04/2015

1
O
hν aq NaOH
N CO2H
acetone EtOH, reflux O
O
NH2
82% >80%

A. G. Griesbeck et al., Org. Lett., 10, 3965 (2008)

CO2Et O
Me Me
1) MeOH, rt
HO2C NH2 82% O O
O
2) aq H3PO4 N N
Me O CHO NC 100 °C H Me
72% O

A. V. Ivachtchenko et al., J. Org. Chem., 71, 9544 (2006)

Me
O microwave OH

toluene OTBS
Me Me OTBS 210 °C Me Me

91%
dr >25:1
 Fukuyama Group - Group Meeting Problems
04/11/2015

1
TIPSO O
Pd(OAc)2 (1.1 eq)
OH OH
MeCN, rt

51%

A. Nishida et al., Tetrahedron Lett., 52, 3079 (2011)

2
F
A (10 mol%)
O KHMDS (10 mol%) O
+ OMe MS4A
O O O
TMSO THF, –78 °C to rt
O OMe
O
89%

A
Cl
Mes N N Mes

L. Candish and D. W. Lupton, J. Am. Chem. Soc., 135, 58 (2013)

3
MeO 1) CSA MeO
O O
toluene, reflux H
S 88% N
MeO N Et MeO O
CO2Me 2) NaH MeO2C SEt
THF, reflux
Br 99%

(Z/E = 4:1) major diastereomer

A. Padwa et al., J. Org. Chem., 68, 929 (2003)

 Fukuyama Group - Group Meeting Problems
04/15/2015

1
CO2Me 1) toluene, reflux CO2Me
O
N N OMe 73% MeO2C
+ + Ph
O OMe
2) BF3•OEt2 O O
Ph Ph CO2Me CH2Cl2, 0 °C H Ph
60%

V. Nair et al., Org. Lett., 4, 17 (2002)

2
O
O OEt
O O H O
In(OTf)3
EtO
MeCN, 0 to 70 °C
HO Ph O Ph
85%, 89% ee H

91% ee

C.-S. Lee et al., J. Org. Chem., 76, 6534 (2011)

O O
O O
mCPBA (2.0 eq.) mCPBA (2.0 eq.)

MeCN Cl3CCN-MeCN (1:1)

0 °C to rt 0 °C to rt

87% 91%

M. Inoue et al., Org. Lett., 12, 4195 (2010)

 Fukuyama Group - Group Meeting Problems
05/09/2015

Ns O
H O
Bn N AlCl3 Ns
N
toluene, 105 °C Bn
Me H Me
68%

R. P. Hsung et al., J. Am. Chem. Soc., 137, 5596 (2015)

2
3) OTMS
TMSO
1) A, PhI(OAc)2 TMSOTf, CH2Cl2 O
O MeOH, rt –78 °C to rt O H
OMe 79% 99%
cyclopropane
2) hν, acetone, rt 4) AIBN, n-Bu3SnH O
OH benzene, 80 °C HH
92% MeO OMe
99%

A
C-C. Liao et al., Angew. Chem. Int. Ed., 41, 4090 (2002)

3
O2 MeO2C CO2Me
O
LiHMDS
S Ph CO2Me Ph
t-Bu N Cu(OTf)2 O
t-Bu
MeO CO2Me THF, –78 to 50 °C Et N S
Et O
88%

H. Wang et al., J. Org. Chem., 80, 2494 (2015)

 Fukuyama Group - Group Meeting Problems
05/19/2015

OEt OMe
O t-Bu N t-Bu
DTBMP, Tf2O H
O PhCl, 0 °C; H
OEt O
N OMe N
O O DIPEA, reflux Me
O H DTBMP
68% O

F. Lèvesque and G. Bèlanger, Org. Lett., 10, 4939 (2008)

2
MeO
MeO O AgOBz (0.10 eq.) OMe O
Et3N (1.0 eq.) N2 hν O
Me
THF, 45 °C H THF, rt
Me H
H sonication
72% Me
95%

B. J. Stoltz et al., J. Am. Chem. Soc., 125, 13624 (2003)

B. J. Stoltz et al., J. Am. Chem. Soc., 126, 24 (2004)

3
Ph N2 Me N
O O Ph
microwave N
N N +
Me
N N
N toluene, 150 °C O
Me
Me Me O Me
80%

Y. Coquerel et al., Org. Lett., 16, 4126 (2014)

 Fukuyama Group - Group Meeting Problems
05/23/2015

1
SF5
F5S
30% aq. H2O2

H2SO4, rt O
O
HO2C
OMe 55%

P. Beier et al., J. Org. Chem., 79, 8906 (2014)

O t-BuOK (2.0 eq)

t-BuOK (0.5 eq) O 18-crown-6 O
Ph Ph
toluene THF, reflux Ph Ph
130 °C (sealed tube) Ph Ph
78%
64%

M. J. Cook et al., J. Org. Chem., 80, 1472 (2015)

3
PhCHO,EtOH, rt; Ph
PhNHOH
NC N CN
H
65%

S. Blechert et al., Tetrahedron, 43, 3237 (1987)

 Fukuyama Group - Group Meeting Problems
06/06/2015

1 Me
N Ts
t-Bu
BuLi
THF-hexane, –78 °C; THF, –78 to 20 °C;
TMSCHN2
CO (1 atm) t-BuCHO Me O
–78 °C –78 to 20 °C N
Ts
80%

S. Murai et al., J. Org. Chem., 66, 169 (2001)

2 Me Me
LDA, THF, –60 °C; O
O
MeI
Me
>90%, dr = >95:5

Hint: Cyclooctane exists in a boat-chair (BC) conformation, which has minimum boat-chair
transannular interactions. Draw conformations of intermediates in this fashion. conformation

W. C. Still and I Galynker, Tetrahedron, 37, 3981 (1981)

 Fukuyama Group - Group Meeting Problems
06/10/2015
solution: K. Murakami
chair: Toma

PhI(OAc)2 (3.0 eq)

I2 (1.0 eq)
NHTs N
DCE, rt Ts

82%

F. Renhua et al., J. Org. Chem., 72, 8994 (2007)

2
N3 O
TMSO 3 TiCl4 N
OMe
CH2Cl2, –78 to 10 °C
CH(OMe)2 H
79%, dr = 1:0.53

F.-M. Zhang et al., Org. Lett., 13, 724 (2011)

3 TMSOTf (2.0 eq.)

PhIO A
CH2Cl2, –20 °C
O
O
H O O
N Me A (1.0 eq.) (10 eq.)
N MeOH (10 eq.) TFA (25 eq.)
MeO
CH2Cl2, –78 °C; –78 to 0 °C MeO Me
Me
MeO 66% Me
er = 95:5
dr = 8:1 MeO
er = 95:5

R. J. Thomson et al., Angew. Chem. Int. Ed., 53, 1395 (2014)

 Fukuyama Group - Group Meeting Problems
06/13/2015

1
O O
Pd(MeCN)2Cl2 (5 mol%) O t-Bu
A (1.1 eq.)
CO2Et
DMF, 120 °C N t-Bu
N CO2Et O
84% A

S. P. Cooper and K. I. Booker-Miburn, Angew. Chem. Int. Ed., 54, 6496 (2015)

2 1) I

1) KOt-Bu (2.5 eq.)* NHTs

n-BuLi (2.5 eq.)* PdCl2(PPh3)2 (5 mol%)
OEt THF, –95 °C; K2CO3, THF, 50 °C OEt
B(Oi-Pr)3, rt 75% Me
Me OEt boronic ester
2) 2) Pd(OAc)2 (5 mol%)
Me HO OH
DMF, 80 °C N Me
toluene, rt 65%
85% (2 steps)

* : theoretically 2 eq.

P. Venturello et al., Eur. J. Org. Chem., 3451 (2006)

 Fukuyama Group - Group Meeting Problems
06/20/2015

1
[Rh(OAc)(C2H4)2]2
(5 mol%) Ph
Ph Ph (±)-binap (6 mol%)
+ H TIPS
THF, 40 °C
H
90% TIPS

T. Nishimura et al., Org. Lett., 17, 2630 (2015)

2
1) LiAlH4 (4.0 eq.)
OH HNiPr2 (4.0 eq.) O
N NH
THF, 60 °C, 88% Cs2CO3 (4.0 eq.)
O C14H14ClNO3 O
Me
2) A (1.2 eq.) 1,4-dioxane, 100 °C
O Et3N (2.0 eq.) O
THF, 60 °C, 64% 67%

O Cl

D. Y. Gin et al., J. Am. Chem. Soc., 128, 10370 (2006)

O n-BuLi HO
O H
TBS Nap 1,4-dioxane TBSO Nap
–25 to 30 °C
Nap = 2-naphthyl
92%
E/Z = 8.1:1
97% ee
K. Takeda et al., Org. Lett., 7, 5913 (2005)
 Fukuyama Group - Group Meeting Problems
07/04/2015

1
Bu3P, toluene, rt;
O
CO2Et
TFAA O
, microwaves, 150 °C; O
NaIO4 CH2Cl2, 0 °C; N
O N3 EtSCH2COCl, rt MeOH-H2O TFA, rt SEt
rt CO2Et
44% 76%
95%

A. Padwa et al., Org. Lett., 7, 1339 (2005)

2
HO
KHMDS, I2
THF, –78 °C to rt; Tf2O, DMAP n-BuLi
iodobenzene
N O CH2Cl2 THF
Ts O N
0 °C to rt –95 °C to rt Bu
Ts
Bu
70% 75%
toluene, 80 °C;
aq KOH, MeOH, 70 °C

49%

R. L. Danheiser et al., J. Org. Chem., 78, 9396 (2013)

3
Ot-Bu
Ot-Bu Me
Me Pb(OAc)4 (2 eq.) AcO
HO
MeCN, rt O
HO H
60% AcO O

S. Arseniyadis et al., Tetrahedron, 54, 5949 (1998)

 Fukuyama Group - Group Meeting Problems
08/01/2015

1 OTMS
OMe
NHAc OMe MeO
1) TosMIC, K2CO3
MeO MeOH, reflux, 64% TMSOTf NHAc
CHO
MeO OMe
2) o-DCB, reflux EtNO2
MeO MeO O
70% –78 to –50 °C
OMe O
60% (brsm)

J. C. Lee and J. K. Cha, Tetrahedron, 56, 10175 (2000)

2
PtCl2 (10 mol%)
Me
Me toluene, 60 °C

88%

N. Chatani et al., J. Org. Chem., 74, 5471 (2009)

 Fukuyama Group - Group Meeting Problems
08/19/2015

1 Ph
NHMe Ph

N i-PrOH, 85 °C;
+ Cl Unsaturated
O2N aq. NaOH, rt aldehyde o-dichlorobenzene N O
200 °C Me
OTIPS 85% microwave OTIPS
NO2 82%
(2.1 eq.) (1.0 eq.)
C. D. Vanderwal et al., Tetrahedron Lett., 56, 3165 (2015)

O O
O O

OMe Cu(SbF6)2 (1.0 eq) OMe

Me CH2Cl2, rt Me

OMe 91% MeO

A. J. Frontier et al., J. Am. Chem. Soc., 129, 8060 (2007)

PPh3 Br
O KOtBu O H

toluene, 100 °C
H
70%

H. Hamersma et al., Tetrahedron Lett., 35, 335 (1994)

 Fukuyama Group - Group Meeting Problems
08/29/2015

1
1) cyclopentadiene
Et3N, TFE-Et2O
–78 °C to rt H O
O 70% ethylene, Grubbs 1st
Br Br cyclobutane
2) Li CH2Cl2, rt
H
THF 50%
–78 to –30 °C
90%

M. Harmata et al., Org. Lett., 7, 2563 (2005)

2
O
[(Cp*RhCl2)2] (2.5 mol%)
O Cu(OAc)2 (2.1 eq.)
Ph Me AcOH (0.1 eq.)
+ O
Me dioxane, 60 °C MeO2C
OH
MeO2C
86% Ph
Me

D. J. Burns and H. W. Lam, Angew. Chem. In. Ed., 53, 9931 (2015)

3 Me
O
Cl n-BuLi
B
Cl THF
Cl –78 to –40 °C
A
Cl
H 1) Br2, CHCl3, rt
N NaH, DMF, rt;
Me
N
B, 80-90 °C 2) aq. NaOH
N Cl N
41% from A 89% N

P. J. Crowley et al., Tetrahedron, 62, 8966 (2006)

 Fukuyama Group - Group Meeting Problems
10/10/2015

Ph
1 Ph
O2N MeAl O O
O
i-Pr i-Pr Raney Ni
Si Ph 2 , H2 (100 psi) N
HO
O
OMe toluene, –78 to –15 °C MeOH, rt H
i-Pr Si O
O 60%, 27:1 51% i-Pr

S. E. Denmark et al., J. Org. Chem., 62, 1668 (1997)

2 O

O Na2S2O8 (2.0 eq.) KOt-Bu (1.2 eq.)

Ph OH
+ I ketone TBS
Ph
acetone-H2O (1:1), 50 °C THF, 0 °C O

TBS 78% 78%

1.8 eq.

X.-H. Duan et al., Org. Lett., 17, 4798 (2015)

3
[Rh(Cp*)(Cl)2]2
(2.5 mol%)
ONHAc Me n-C9H19 CsOPiv (0.25 eq) n-C9H19
O
+ Me
MeOH, rt

86%

Cp* = C5Me5

J. Wang et al., Angew. Chem. Int. Ed., 53, 13234 (2014)

 Fukuyama Group - Group Meeting Problems
10/14/2015

1 Cl
Cl
O CN
K2CO3
O H
ethylene glycol CN
H2N 120 °C, µw
CHO
(2 equiv) 87% NH2
HN H
O
O N
H
G. Li et al., J. Am. Chem. Soc., 131, 11660 (2009)

C6H13 Ti(Oi-Pr)4 C6H13

i-PrMgCl (2 eq.)
OH
Et2O, –78 to 0 °C Et
H OH
OCOEt 76%

F. Sato et al., J. Am. Chem. Soc., 125, 4036 (2003)

3
N N
SO2
N N
t-Bu PtCl2 (10 mol%)
O O
Cs2CO3 toluene, 80 °C;
MeO CHO MeO
THF-DMF Grubbs 1st (5 mol%)
70 °C CH2Cl2, reflux;
Ethyl Vinyl Ether
80%
64%

A. Fürstner and C. Aïssa, J. Am. Chem. Soc., 128, 6306 (2006)

 Fukuyama Group - Group Meeting Problems
10/21/2015

1
H
O N
Me
O O CN CO2Et (2.0 eq.)
HS Me
EtO2C
DBU (1.0 eq.)
N N
H
CH3CN, 80 °C N CO2Et
S S O
Cl 84%

Cl

Q. Liu et al., J. Am. Chem. Soc., 133, 1775 (2011)

Me O
Me O O HO2C
Me O O
BF3•OEt2 (1 eq.) BF3•OEt2 (1 eq.)
N DCE, 80 °C; N
DCE, 80 °C;
Ts PIDA (1.1 eq.), rt PIDA (2.1 eq.), rt Ts
NHTs
78% 88%

Y. Du et al., Org. Lett., 17, 5252 (2015)

3
Ph
OMe Ph 1) MeOH, reflux OMe N
H R O
75% R OH
+ + N
O CN
NH2 2) Cl CO2Et N CO2Et
MeO O MeO
O O
(R = n-Hex) toluene, reflux
68%

J.-P. Zhu et al., Org. Lett., 3, 877 (2001)

 Fukuyama Group - Group Meeting Problems
11/04/2015

IPrAuCl (5 mol%) NTs i-Pr i-Pr

TsO AgBF4 (5 mol%)
+ NTs Bu N N
Bu IPr =
Ph DCE, 60 °C
t-Bu
Ph i-Pr i-Pr
85 %

M. Gonzales et al., Org. Lett., 11, 13 (2009)

2
Me
HO (10 mol%)
S N BnCl

O NBS (1 eq) O2N

DBU (1.2 eq) O
H + Ph
DMSO, rt Ph
O2N O
72%

A. Sudalai et al., Angew. Chem. Int. Ed., 54, 14150 (2015)

3
Br O O
BrMg
aq HCHO
CuCN p-TsOH TsNHNH2 NaH
H
THF, rt THF, rt MeOH toluene
Me 10 °C reflux
81% (2 steps)
81% 49%

H.-Y. Lee et al., Org. Lett., 16, 2466 (2014)

 Fukuyama Group - Group Meeting Problems
11/11/2015

1
Ph
OTMS (20 mol%) Br NO2
N Ph (1.3 eq) NO2
OH H
CHO H CHO
PhCO2H (10 mol%) Et3N (1.3 eq)
S S
OMe CH2Cl2, 40 °C; 0 °C to rt S
HO
45% MeO
dr = 100:0
er = 95:5

C. D. Risi et al., J. Org. Chem., 80, 9176 (2015)

1) Bu3Sn-TMS
CsF•CsOH
Me THF, 25 °C Me
43% O

Br 2) O3, CH2Cl2 –78 °C;

O Me2S, –78 °C to rt O OH
57%

M. E. Jung and P. Davidov, Org. Lett., 3, 627 (2001)

TBSOTf
KHMDS
C2H5CHO TBSOTf Et2O
OH O OBn SmI2 2,6-lutidine –80 to 0 °C; O OH OBn

THF CH2Cl2 HF, MeCN HO

–25 to –15 °C –78 to 0 °C rt

87% 91% 85%

T. Chen and K.-H. Altmann, Chem. Eur. J., 21, 8403 (2015)
 Fukuyama Group - Group Meeting Problems
11/25/2015

1
Ni(COD)2 (5 mol%)
A (5 mol%)
O PPh3 (5 mol%) t-Bu
AlMe3 (40 mol%) O
Ph H N N H
N H Ph N Me t-Bu P
toluene, 40 °C OH
91%, 93% ee

P. A. Donets and N. Cramer, J. Am. Chem. Soc., 135, 11772 (2013)

2
O
O H2NSO3CH2CCl3, MgO
Cl3C O
[Rh(CF3CONH)2]2, (4 mol%) O
PhI(OAc)2 TFA O S O
O N
toluene, 0 °C to rt CH2Cl2, 0 °C
MeO
80% 90%
MeO

S. Hanessian et al., Org. Lett., 12, 1816 (2010)

3
OBn

O
NHBoc Hg(OTf)2 (0.2 eq.) OTBS
O
MeCN, –20 to 0 °C BnO R
R OTBS NBoc
78%

R = (CH2)5CH3

Y. Morimoto et al., Org. Lett., 17, 5772 (2015)

 Fukuyama Group - Group Meeting Problems
12/05/2015

OTs
AcONa

AcOH, reflux
OAc
85%

D. Whittaker et al., J. Chem. Soc., Perkin Trans. 2, 789 (1999)

2
O Me
H
Me MgBr NaHCO3 O
O O O
Me
THF, 0 °C mesitylene, reflux O
O N
Me Me
Me
60% O
69%

P. A. Jacobi et al., J. Org. Chem., 55, 202 (1990)

3
(HCHO)n (5.0 eq) * CO2Me
CO2Me (4.0 eq) **
toluene, 100 °C;
N
N CO2H
H Bu2SnCl2 (0.1 eq)

78% MeO2C
* theoretically 1.0 eq
** theoretically 2.0 eq

H. Ardill et al., Tetrahedron, 50, 5067 (1994)

 Fukuyama Group - Group Meeting Problems
12/16/2015

1
1) p-TsSMe, LDA
O THF, –78 °C to rt OH
Br 74% DBU

2) toluene, rt
MgBr Me
MeO Me
THF, 0 °C to rt; 85% SMe
2 M HCl aq., rt
88%

W. Shao and D. L. J. Clive, J. Org. Chem., 80, 12280 (2015)

2
1) n-BuLi, HMPA
THF, −78 °C;
Br O Ph
O O
Ph
O 45%
N O
• 2) xylene, 135 °C N
48% Me
Bn O Bn

P. Hsung et al., Org. Lett., 12, 1152 (2010)

3
1) (HCHO)n (3.2 eq.)
Na2CO3 Cl Mg (2.0 eq.)
THF; O
H H2O, reflux, 68%
Cl
CO2 OH
O 2) SOCl2, pyridine
80% Cl
74%

E. L. McCaffery and S. W. Shalaby, J. Organomet. Chem., 8, 17 (1967)

 Fukuyama Group - Group Meeting Problems
12/19/2015

1
O Rh2(pfb)4 (2.0 mol%)
TBSO O CH2Cl2, MS4A MeO
N
0 °C to rt;
HN O
OMe
OMe SiO2 O
N2 MeO
92%
O

F F O
F
OH
F
F F F
pfb

M. P. Doyle et al., Org. Lett., 14, 800 (2012)

2
PPh3 (2.5 eq), CBr4 (2.8 eq) Me
O Et3N (2.0 eq), CH2Cl2, 0 °C;
Ph
B OCONH2 HN
O PhCHO (1.2 eq), 0 °C to rt; O
Me aq NaHCO3, rt
O
56%, 99% ee

B. Carboni et al., Angew. Chem. Int. Ed., 55, 1025 (2016)

3
OH [Rh(OH)(cod)2] HO Ph
Me Me Me
rac-DM-BINAP
Ph
N N
S toluene, 60 °C S Me
O O Me
O O
99%
er > 99:1, dr = 20:1 er > 99:1, dr > 20:1

M. Murakami et al., J. Am. Chem. Soc., 135, 19103 (2013)

 Fukuyama Group - Group Meeting Problems
01/06/2016

1
Ph

N
Ac A
Ph
Ph
O Pd(PPh3)4 (8 mol%)
TsNHNH2 Cs2CO3 H
H
toluene, 60 °C; toluene, 80 °C
N
88% (based on A) Ac

J. Wang et al., Org. Lett., 19, 5032 (2013)

2
t-BuO (4.0 eq) Ot-Bu
NO2 N
Ph3PAuNTf2 (5 mol%)
O
DCE, rt

83% O

R.-S. Liu et al., J. Am. Chem. Soc., 133, 1769 (2011)

3
TIPSO Z Z
W(CO)6 (5 mol%)
Et3N (10 mol%) TIPSO
HZ Z
MS 4A, hν
Ph Ph
toluene, rt

83% Me
Me
Z = CO2Me
N. Iwasawa et al., Chem. Eur. J., 16, 10785 (2010)
 Fukuyama Group - Group Meeting Problems
01/20/2016

1
N2
O N NH
Li TMS (2.2 eq.)
TMS
THF, –78 °C to rt
Ph Ph
81%

D. Lee et al., Angew. Chem. Int. Ed., 55, 2222 (2016)

2
OH
TFA O Me
OAc N
N rt
N
H Me N
OH H
61%

J. Jiricek and S. Blechert, J. Am. Chem. Soc., 126, 3534 (2004)

3
O
O
O
neat O
122 °C; 1,2-dichlorobenzene
O OBn O
TBSCl 250 °C OBn
OH O H
O imidazole microwave TBSO
O CH2Cl2, rt
91%
OTBS
74%, dr = 10:1

P. A. Wender et al., Nature Chem., 3, 615 (2011)

 Fukuyama Group - Group Meeting Problems
02/06/2016

1 MeO2C
MeO2C O
[Rh(dppe)]ClO4 H CO2Me
(10 mol%)
CO2Me
DCE
reflux H

44%
OHC

Y. Sato et al., Tetrahedron Lett., 47, 5617 (2006)

2
nBuMgBr
Et2O, rt; ZnBr2 Me
THF, rt; TMS
TMS
1N HCl aq. OTMS
O −5 ºC
TMS
reflux 89%

I. Marek et al., Org Lett., 7, 5313 (2005)

3
OMs O
O O 1) NH2NH2·H2O TBSO
neat, rt OAc

O O 2) TBSOTf, py O O
CH2Cl2, 0 °C
85% (2 steps)
3) Pb(OAc)4 (3.0 eq.)*
toluene, rt
48%
* theoretically 2.0 eq

A. Vassella et al., Helv. Chim. Acta, 87, 2405 (2004)

 Fukuyama Group - Group Meeting Problems
02/24/2016

PtCl2 (10 mol%) Me

AcO Me
COD (20 mol%)
O
O toluene, 100 °C
H
H OAc
75%

R. Sarpong et al., J. Am. Chem. Soc., 128, 6787 (2006)

O O
O Me
CONHBn hν pTsOH•H2O, MeOH Me OMe

THF; toluene, 105 °C Me OMe

Me CO2Me H2SO4
THF-MeOH, rt 90% O O

50%, 75% ee
(>95% ee after recryst.)

P. S. Baran et al., Angew. Chem. Int. Ed., 45, 249 (2006)

3 1) Propose the synthesis of Garner's aldehyde.

2) Explain the selectivity of carbonyl addition by using Felkin-Anh model.

a) Li TMS
O THF, –78 °C to rt OH OH
L-serine
4 steps 75%, A:B=8:1
methyl ester H + O
O O
hydrochloride
NBoc b) Li TMS NBoc TMS NBoc TMS
(C4H9NO3•HCl)
ZnBr2
Et2O, –78 °C to rt A B
You may use these reagents. 89%, A:B=1:11
Boc2O, BF3•OEt2, (COCl)2, LiAlH4
iPr2NEt, DMSO, Me2C(OMe)2
A. Dondoni and D. Perrone, Org. Synth., 77, 64 (2000)
P. Herold, Helv. Chim. Acta, 71, 354 (1988)
 Fukuyama Group - Group Meeting Problems
02/27/2016

1
O
CO2Me 1) NaH, THF
O
reflux, 79% TsOH (10 mol%) O
+ EtO2C
2) LiCl, 6 M HCl aq. m-xylene, reflux
Ph DMSO
120 °C, 83% 80% Ph

D. J. Dixon et al., Org. Lett., 13, 664 (2011)

2
1) IPrAuNTf2 (5 mol%) O
Ph O CH2Cl2, rt
+ OEt Ph
n-Bu HO n-Bu
2) TsOH (20 mol%)
acetone/H2O, rt
89% (2 steps)

L. Zhang et al., J. Am. Chem. Soc., 130, 6944 (2008)

3 Boc Boc
NHBoc O TMS-EBX n-BuLi (1.0 eq.)
R TBAF (2.4 eq.) THF, –78 °C; N N
n-hexyl
BocN N
THF-CH2Cl2 A (1.8 eq.), –78 °C; N R
BnO2C
OTBS –78 °C DMPU, –78 °C H H O
O
80% (3 steps) >49%

O O
O OBn
n-hexyl MeN NMe
O O I LiO
O TMS
R TMS-EBX A DMPU

J. Waser et al., Chem. Eur. J., 16, 9457 (2010)

S. B. Herzon et al., Nature, 525, 507 (2015)
 Fukuyama Group - Group Meeting Problems
03/09/2016

1
n-Bu
Ph N Ph Ph
H Ph H CO2Me n-Bu
N
azetine
(OC)5Cr THF, 0 °C CH3CN, 80 °C O Ph
Ph MeO2C
62% 82%

M. Tomás et al., Angew. Chem. Int. Ed., 49, 1306 (2010)

2
1) HO
I
n-Bu3SnH, Et3B, O2
CH2Cl2, rt 1) RuO2•H2O, NaIO4 HO2C CO2H
Boc
N 78% EtOAc-H2O, 0 °C
Ts
2) Na/Hg, B(OH)3 2) Jones' reagent N CO2H
MeOH, reflux acetone, rt Boc
>77% (3 steps)

M. D. Andrews et al., Org. Lett., 7, 815 (2005)

3
vinyl bromide(2.0 eq.)
LDA (2.0 eq.) LDA (2.7 eq.)
THF, –95 °C; THF, –78 °C to rt;

Bpin I2 TIPSCl, rt
MeOH, –95 °C to rt TIPS
65% (2 steps)

V. K. Aggarwal et al., Angew. Chem. Int. Ed., 55, 4270 (2016)

 Fukuyama Group - Group Meeting Problems
03/19/2016

1
O
O
MeO2C CO2Me O
N2
[Rh(CO2C7H15)2]2
MeO2C
N CH2Cl2, rt MeO2C H
O 70%, dr = 1:1 N

A. Padwa et al., Tetrahedron Lett., 34, 7853 (1993)

2
1) BF3•OEt2,
O Ac2O, rt, 73%
2) aq. NaOH, MeOH, rt; O
Me Me
aq. HCl; FeCl3, quant. MeCN, reflux;
zwitterion
(C14H11IO3)
Me 3) PhI(OAc)2 H2O Me
CH2Cl2, 0 °C, 60% O
O 52%

A. Varvoglis et al., Tetrahedron Lett., 35, 8449 (1994)

3
O'Shea's reagent OMe
OMe Cu(OAc)2 CO B
O pyridine [Rh(CO)2Cl]2 O H O O
B B
O
naphthane CH2Cl2, rt toluene, 80 °C N
O
reflux
88% 80%
89% O'Shea's reagent

Y. Feng and Z.-X. Yu, J. Org. Chem., 80, 1952 (2015)

 Fukuyama Group - Group Meeting Problems
04/06/2016

1 I
CF3

Me O
(1.5 eq.) O
Cu2O (25 mol%) Me
N O 2,2'-Bipy (50 mol%) N
O S O Ph CF3
MeCN, 80 ºC
Ph
70%

C. Nevado et al., J. Am. Chem. Soc., 137, 964 (2015)

2
1) Me2SO4 NHMe
xylene, reflux
Me N
N 2) 50% aq. H2SO4, 100 °C toluene, reflux
OEt N Me
89% (2 steps) 79%
O

A. Schmidt et al., Angew. Chem. Int. Ed., 49, 2790 (2010)

3
NHMs
MsN3, CuTC O
1,2-DCE, 0 °C;
+ OPh
N MW, 80 °C;
Me
Amberlyst 15, 50 °C N
Me
87%

H. M. L. Davies et al., J. Am. Chem. Soc., 136, 10266 (2014)

 Fukuyama Group - Group Meeting Problems
04/09/2016

O HO
TBSO O Rh2(pfb)4 (2.0 mol%)
N2 O
MS4A cyclo DIBAL (6.0 eq)*
+ N O
OMe propane
CHCl3, rt THF, rt;
N2
H2O
O 80% MeO Me
91%
(1.0 eq) (1.5 eq)
* theoretically 3.0 eq

M. P. Doyle et al., Angew. Chem. Int. Ed., Early View

DOI: 10.1002/anie.201601260

OH Rh2(OPiv)4 (1.0 mol%)

O NTs
NTs TFA (50 mol%)

DCE, rt
OH H
88%
S. Zhu et al., Org. Lett., 18, 1322 (2016)

3
Me
1) MgBr
Me
Me (5 eq.)
THF
OH –78 to 0 °C
CF3 FVP H
O 2) pTsOH
CH2Cl2, rt (430 °C, 0.05 Torr)
O
88% (2 steps)
99%
O O CF3

M. Pohmakotr et al., J. Org. Chem., 80, 10512 (2015)

 Fukuyama Group - Group Meeting Problems
04/19/2016

1
Ph
IPrCuCl (5.0 mol%) Ph O
OH O2 (1 atm) NH
O N DBU (1.1 eq.)
N + N
• Ph Ph toluene, rt toluene, 100 °C Me
HO N Ph
O N
94% 84% H
(1.0 eq.) (1.2 eq.)

R. S. Liu et al., Org. Lett., 18, 412 (2016)

2
O
O O

O CN
N
toluene, 150 °C
sealed tube
Si(i-Pr)3
62%
Si(i-Pr)3

T. Sakai and R. L. Danheiser, J. Am. Chem. Soc., 132, 13203 (2010)

O O
O2 (10 atm)
I2
PhI(OAc)2 1) TBAF
hν THF, rt O
O O O
cyclohexane 2) TPAP, NMO
O O
O H O CCl4 CH2Cl2, MS4A H O
45 °C rt, 17% (3 steps) O
HO OTES O
H H

M. Hirama et al., Angew. Chem. Int. Ed., 54, 8538 (2015)

 Fukuyama Group - Group Meeting Problems
05/07/2016

1 n-BuLi (1.1 eq)

OEt Cl Cl chiral ligand (4 mol%) 1) TBAF (2.2 eq)
Si (0.5 eq) NaOt-Bu (4 mol%) THF, rt
OEt O
THF, –78 °C; Ni(cod)2 (2 mol%) 2) PCC (2.0 eq)
Br 1M HCl, rt THF, 60 °C CH2Cl2, rt O
65% (2 steps)
89% 100%
87% ee
BF4
N N

Ph Ph
chiral ligand S. Ogoshi et al., J. Am. Chem. Soc., 137, 11838 (2015)

2
OTIPS O
ZnI2 (10 mol%) Ph
ClCH2CH2Cl , 70 °C;
Ph Ph H2O, 70 °C Ph

97%

J. Wang et al., J. Org. Chem., 79, 6286 (2014)

MgBr
LDA (2.2 eq.) HO
O O Et2O, –78 °C to rt;
THF, –78 °C;
N O OMe NH4Cl aq., rt Ph
OMe
(OC)5Cr Ph
80% O
THF, –78 °C;

J. Barluenga et al., Angew. Chem. Int. Ed., 49, 9720 (2010)

4 Me OHH
OTIPS Me 1) TiCl(Oi-Pr)3, c-C5H9MgBr
H H
THF O
Me N
PMP
2) SiO2*, CF3CH2OH*;
O
P(OEt)3, 68% (2 steps) H
OTIPS
*SiO2 and fluorocarbon solvents possess high solubility of oxygen

J. K. Cha et al., J. Am. Chem. Soc., 123, 11322 (2001)

 Fukuyama Group - Group Meeting Problems
05/14/2016

1 O
O
TMSCF3 O
F i-Pr2NEt
F S N SCF3
F CH2Cl2, –20 °C; 1,4-dioxane, –10 °C

54%

N. Shibata et al., Chem. Sci., 7, 2106 (2016)

2
COOBu
CO2 (1 atm)
CoI2(dppf) (10 mol%)
Zn powder (1.5 eq)
Zn(OAc)2 (20 mol%) Me COOH
Bu4NI (20 mol%) MeI Ph
Ph Ph
CH3CN, rt; DMF, rt COOBu
Ph
88%

Y. Tsuji et al., J. Am. Chem. Soc., 138, 5547 (2016)

3
Cp2ZrCl2 (2.0 eq.) *
Me2PhSiLi (4.0 eq.) ** Me
Ph Ph Si Ph
THF, –78 °C to rt;
CuCl (4.0 eq.) ** Ph Ph
AllylCl (4.0 eq.) **

76%
* theoretically 1.0 eq.
** theoretically 2.0 eq.

M. Mori et al., J. Am. Chem. Soc., 123, 4139 (2001)

 Fukuyama Group - Group Meeting Problems
05/21/2016

1) TsN3, DBU
MeCN, 0 ºC H
MeO Ph N
N O 94% Ph

Ph Ph 2) Rh2(OAc)4 (2.0 mol%)

DCE, 60 ºC MeO2C
94%

C. Park et al., J. Am. Chem. Soc., 134, 4104 (2012)

2
1) O

Cl
1)
OEt
Na2CO3
BSA (3 eq) CO2Me
CH2Cl2, 0 to 20 ºC
5 to 20 ºC 86%
O2N Oxazine
CO2Me N
2) MeOH 2) toluene, reflux
CH2Cl2, 20 ºC 80%
cis : trans O
52% (2 steps)
=1:2

H.-U. Reissig et al., Synlett, 6, 863 (2002)

3
O
Et
H
HO O
O N
NO2 K2CO3 Et

H2O, rt O
O
89%, dr = 3:1

J. C. Menéndez et al., Org. Lett., 7, 2197 (2005)

 Fukuyama Group - Group Meeting Problems
06/08/2016

O I2 (3.0 eq.) ** S
O Cu(NO3)2•2H2O (25 mol%)
+ HO S
ONa•2H2O DMSO, 100 ºC
O
O
(2.0 eq.) 72%
(4.0 eq.) *
* theoritically 1.0 eq.
** theoritically 2.0 eq.

A. X. Wu et al., Org. Lett., 18, 412 (2016)

Ts Pd(PPh3)4 (10 mol%)

N Ts
2,6-dimethylphenol (20 mol%) N

dioxane, 85 °C TIPS
TIPS
70%

Y. Zhang et al., Org. Lett., 12, 1840 (2010)

3
N2
NH2OH·HCl Ph CO2Me
NaOH O Ph
O t-BuOH-H2O, rt; Rh2(OAc)4 (2 mol%)
Ph
Et TsNClNa·3H2O; toluene
Ph 60 °C to reflux; Et N CO2Me
DDQ, rt
Cu, CuSO4
84%
73%

J. R. Manning and H. M. L. Davies, J. Am. Chem. Soc., 130, 8602 (2008)

 Fukuyama Group - Group Meeting Problems
06/18/2016

1
OAc
[CpRuCl(cod)] (10 mol%)
Ph TBAC (10 mol%) hν
O O
AcOH (1.2 eq.) I2 (1.1 eq.)
Ph
1,4-dioxane, 50 °C toluene-THF (4:1), rt
Ph

M. Shibuya et al., Chem. Eur. J., 21, 9093 (2015)

2
Ph Ph
Ph3PAuNTf2 (5 mol%) N
Ph MS 4A, B (1.4 eq.)
N N
+
i-Pr O
Ph toluene, 50 °C
N OH N B
Me imine A (1 eq.) 79% based on imine A Me O
1.3 eq.

Y. Liu et al., Angew. Chem. Int. Ed., 52, 13302 (2013)

3
1) DCC, NHS cyclopentadiene H
O CH2Cl2, 0 °C NaIO4 Grubbs-II (10 mol%) N O
MeOH-H2O toluene, 80 °C H O
HO 2) NH2OH•HCl
Et2O-H2O, 0 °C 0 °C to rt
75%
61% (3 steps)

G. Vincent et al., J. Org. Chem., 75, 4333 (2010)

4
H
O O
H
N hν AcOH, pyridine BocN
hemiaminal
ether H
N CH2Cl2 CH3CN, rt CH3CN N
H
Boc 0 °C to rt reflux

>85% 58% (2 steps)

J. D. Winkler et al., Tetrahedron, 54, 7045 (1998)

 Fukuyama Group - Group Meeting Problems
06/22/2016

1 1) IBX
TBSO EtOAc, reflux Me O
Me Me AuCl3 (5 mol%) 93%
C12H20O2 Me
Me MeOH, reflux 2) BF3·OEt OH
Me
OH CH2Cl2, rt H
86% 90%

C. Nagaraju and K. R. Prasad, Angew. Chem. Int. Ed., 53, 10997 (2014)

2
CuPF6 (4 mol%)
OH O
NHt-Bu (8 mol%)
t-BuHN t-Bu O

CH2Cl2, O2, 25 °C
O
t-Bu 98% t-Bu

X. Ottenwaelder et al., Inorg. Chem., 54, 8665 (2015)

Ph K2CO3 TMSOTf, DTBP

N
Me toluene toluene, 100 °C Me N
O microwave
170 °C 92% O

55%

K. N. Houk et al., J. Am. Chem. Soc., 137, 6956 (2015)

 Fukuyama Group - Group Meeting Problems
07/02/2016

1
1)
MeO CN

O TMSOTf O
MeNO2, 0 °C Me OMe
O hν Ph
80%
Me OMe
MeCN, rt 2) MeOH, 100 °C
OMe Pyrex N
84% H
Ph O
99%

J. A. Jr. Porco et al., J. Org. Chem., 76, 9792 (2011)

CuI (10 mol%) Br (10 eq.)

Ph Et4NI (10 mol%)
Ph
LiOH (1.5 eq.) PdCl2 (3 mol%)
TsN3
THF-tBuOH, 10 °C; DMF, 60 °C Ph
CHO NH4Cl aq. O
Ph N
81%
62%

C. Ma et al., Org. Lett., 16, 1822 (2014)

CO (1 atm)
Me [Rh(cod)Cl2] (3.75 mol%) Me
P(3,5-(CF3)2C6H3)3 (15 mol%) O
Na2SO4 (20 mol%)
Me
Me N PhCN, 130 ºC N
H
O
O NMe2 71% NMe2
(dr = 3:1)

F. Bower et al., Tetrahedron, 72, 2731 (2016)

 Fukuyama Group - Group Meeting Problems
07/13/2016

1
1) TMSCF2Br (2.5 eq.)*
O O TBAB, (5 mol%) O
O
toluene, 110 ºC F
Me OEt
2) CuCl (1.1 eq.) F OEt
MeS SMe DCE, 70 ºC SMe
82%
* theoretically 1.0 eq.

M. Wang et al., Org. Lett., 18, 3414 (2016)

2
Ph RSO2H SO2R
TBHP (0.4 eq.)
Ph
DMF, 80 ºC N
N3 H
93%

R = Me

B. Han et al., Org. Lett., 18, 3330 (2016)

Me
HO AgOAc (2 mol%) TMSN3, BiCl3 Pd(OAc)2 (5 mol%)
N
DCE, 60 ºC; 60 ºC; 80 ºC
Ph Ph
NHTs N
82% H

S. S. V. Ramasastry et al., Angew. Chem. Int. Ed., 55, 7737 (2016)

 Fukuyama Group - Group Meeting Problems
07/20/2016

1 PMP [(S,S,S)-LAuCl] (5 mol%) PMP

AgSbF6 (5 mol%) TsNHNH2 MeO
+ N N
CH2Cl2, –15 °C MeOH, 90 °C N
O
O 70% Ts
(1.5 eq) 92%
94% ee

Ar
Ph
O Ar = 3,5-(CF3)2C6H3
P N
O (S,S,S)-L
Ph J. Zhang et al., Angew. Chem. Int. Ed., 53, 13751 (2014)
Ar

OH C6H4p-Br
N AgOTf (10 mol%) O
+ p-BrC6H4 N
DMF, 75 °C
Ph Ph
83%

J. Wu et al., Org. Lett., 14, 3430 (2012)

3 MeO2C Me
BF4 MeO2C
S
Me SMe
O H
CH3CN, –40 °C;
OAc O
MeS Et3N, rt O
O MeS N
N
MeS 80% (dr = 1:1)

A. Padwa et al., Org. Lett., 4, 1515 (2002)

 Fukuyama Group - Group Meeting Problems
08/03/2016

1 Fe(OTf)3 (1.15 mol%) O

ligand (1.15 mol%)
t-Bu t-Bu
O2 (1 atm), DCE
75 °C, 8 h

87% (10% SM)

N N
Ph N Ph
Fe(OTf)3 (1.15 mol%) O
ligand (1.15 mol%) NH HN
Br Br Ph Ph
O2 (1 atm), DCE ligand
75 °C, 16 h

61%
(with Ph2S, 97%) J. Xiao et al., J. Am. Chem. Soc., 137, 8206 (2015)

2
O
Me
S 9
SNO S
PPh2 (5 eq.) 9 Me
MeO MeO
NHCbz MeCN-PBS buffer (pH = 7.4) NHCbz
O rt to 50 °C O
57%

M. Xian et al., Org. Lett., 12, 5674 (2010)

3 O N
Ph Ph

KOt-Bu
NH2 AcOH hν
O N
MeCN, 40 °C MeCN, rt N
CN evap; Ph
CN
88% Ph
CN

O
S. Pusch and T. Opatz, Org. Lett., 16, 5430 (2014)
 Fukuyama Group - Group Meeting Problems
08/27/2016

1
O
Cl H Me
O Me3OBF4
MeNO2, rt; N Bn
Et3N
CN Me
N
CH2Cl2, rt NaBH(OAc)3 N O
Bn H Me
0 °C to rt HO
87%
68%, dr = 98:2

S. A. Habay et al., J. Org. Chem., 77, 10416 (2012)

2
O
O Me3S(O)I (3.8 eq.)*
NaH (3.2 eq.)* OMe
OMe
DMSO, rt O
O
O O
76%

* theoretically 2.0 eq.

M. Yamashita et al., Org. Lett., 14, 6048 (2012)

3
TMSN3 (1.5 eq.)
Bu2SnO (0.25 eq.)
N
N CN N N
toluene, 60 °C
HN N
Me O Me O
80%

TMSN3 (1.5 eq.)

Bu2SnO (0.25 eq.)
CN toluene, 60 °C;
N Boc
Boc2O, 60 °C N
Bn
Bn
86%

F. Couty et al., Chem. Comm., 52, 10072 (2016)

 Fukuyama Group - Group Meeting Problems
09/07/2016

N2 EtO2C
In(OTf)3 (1.0 eq.)
EtO2C OH
MS4A CsF (2.5 eq.)*
OTMS N
Boc
CH2Cl2, rt MeCN, reflux H
N TMS
Et 60% Et
90%
* theoretically 1.0 eq.
M. Brewer et al., Org. Lett., 18, 3952 (2016)

2
H2 H H
MeO Cs2CO3 Pd/C N N
O
MeCN, 65 °C MeOH, rt

90% 80%
 H2
Cs2CO3 Pd/C
O
NsHN MeCN, 65 °C MeOH, rt
OMe
90% 80%

S. Canesi et al., Org. Lett., 18, 4348 (2016)

3
Me
Me
O Me
[RhCl(coe)2]2 Me
O O
Me2N PEt2 NaHB(OAc)3 O
N AcOH
N
toluene, 55 °C; EtOH, 0 °C
OTBS
Cl 69%
dr = >20:1
Cl
TBSO
J. A. Ellman et al., Angew. Chem. Int. Ed., 54, 12044 (2015)
 Fukuyama Group - Group Meeting Problems
10/01/2016

1
Me
N Ph Rh2(OAc)4 Me2AlCl Ph
N
O
Ph DCE, 130 °C CH2Cl2 HO
sealed tube;
68%, dr = >20:1

J. A. May and B. M. Stoltz, J. Am. Chem. Soc., 124, 12426 (2002)

O HO O
Ph Ph Ph
NH α Ph
cyclopentenone H
O Me THF, rt; toluene, 160 °C Me
α
evap.; sealed tube N

84%, dr = 5:1 (αα/αβ)

A. J. Frontier et al., Org. Lett., 18, 4896 (2016)

3
O

CHO O
NO2
N
H
O2N
O H
AcONa N CO2H
Me O
N CO2H azlactone
H Ac2O, 100 °C EtOH, reflux Me N O

94% 87% N
N O
H

D. Q. Shi et al., ACS Comb. Sci., 16, 139 (2014)

 Fukuyama Group - Group Meeting Problems
10/08/2016

1
TfOH
CH2Cl2 H O
O 0 °C to rt; N
+ N3 Ph N O
O Ph
Ph N NaOH, H2O. rt
O
Ph
78%

N. Maulide et al., Chem. Sci., 7, 6032 (2016)

2
Ph Ph
toluene, 100 °C; MeO2C
N Cy N
PPh3 (10 mol%), 60 °C; Cy
air, 0 °C
MeO2C OH
80 %

M. Yoshida et al., Angew. Chem. Int. Ed., 53, 14550 (2014)

3
CO2Me
CO2Me HO
O2 (1 atm)
+
NH2 DMSO, 80 °C CO2Me
CO2Me
N
89% H

N. Jiao et. al., J. Am. Chem. Soc., 138, 13147 (2016)

 Fukuyama Group - Group Meeting Problems
10/15/2016

1
PdBr2 (10 mol%)
BINAP (10 mol%)
Li2CO3 (2.0 eq) O
t-Bu
N O O
TBAB, MS4A
t-Bu Me N
NMP
I Br 150 °C
Me
62%

Y. Chen et al., Org. Lett., 17, 5578 (2015)

O
N O pyrrolidine (2.0 eq) BnNH2 O2N
N CHCl3, rt; MeCN, 120 °C
H O BnHN N Me
N O MVK
63%
quant

N. Nishiwaki et al., Tetrahedron, 70, 6522 (2014)

3
HO Me SMe OMe
H
SMe
Me SnCl4
H Me
MeNO2, rt H
SMe
78% Me
MeO SMe

H. Junjappa et al., J. Chem. Soc., Perkin Trans. 1, 1547 (2000)

 Fukuyama Group - Group Meeting Problems
11/05/2016

1
O
O
PO(OMe)2 DBU (2.0 eq.) N
O +
N2 MeCN, rt NH
Br 84% PO(OMe)2
(2.0 eq.)

R. Namrata et al., J. Org. Chem., 81, 11291 (2016)

2
Me Pt(dba)3 (1.0 mol%)
(S,S)-ligand (1.2 mol%) OHC Me HO
Me
B2(pin)2 O
(S)-bis(boryl) intermediate
toluene, 60 °C; 60 °C * * Me
Me
Me Me 68% OH Me
*dr = 5:1
er = 96:4
Ar Ar
Me O O
P Ph
Me O O
Ar Ar
Ar = 3,5-diisopropylphenyl J. P. Morken et al., J. Am. Chem. Soc., 135, 2501 (2013)
(S,S)-ligand

Ph Ph
O
CO2Et H
i-PrNC + +
• toluene O
reflux O N
i-Pr
EtO
57%

J. Li et al., Org. Lett., 16, 5604 (2014)

 Fukuyama Group - Group Meeting Problems
11/19/2016

(Ph3P)AuCl (2 mol%) HH
AgSbF6 (2 mol%)

CH2Cl2, rt
AcO
OAc
98%

M. Malacria et al., Org. Lett., 9, 2207 (2007)

OTIPS ReI(CO)5 TIPSO

(2.5 mol%) O
OBn MS4A
Me + O
O 1,4-dioxane
Me
100 °C Me
O Me
90%

H. Sogo and N. Iwasawa, Angew. Chem. Int. Ed., 55, 10057 (2016)

3
O
∗ H
hν (254 nm)
N H
O MeCN
TBSO O
57% N
H H
>98:2 dr

K. I. Booker-Milburn et al., Org. Lett., 18, 5608 (2016)

 Fukuyama Group - Group Meeting Problems
11/26/2016

1
visible light 2,2-DMP NH2NH2
t-Bu Me CH2Cl2, –78 °C; p-TsOH 100 °C; t-Bu
N O
+ O O
OsO4, NMO, p-TsNH2 CH2Cl2 CuCl2 O
N N H2O, acetone 40 °C aq. NH3
10 equiv. – 78 to 0 °C 25 °C
1 equiv.
74%
70% 90%
D. Sarlah et al., Nature Chem., 8, 922 (2016)

Ph Ph
BF3·OEt2
N3 (30 mol%) POCl3 O
O
Ph CH2Cl2, rt DMF, 100 °C
Me Me
OH Ph
Ph 80% 81%
X. Bi et al., Org. Lett., 17, 6190 (2015)

3
[RhCp*Cl2]2 (3.0 mol%)
AgSbF6 (40 mol%) OH
O MS4A
O Ph
+
Ph N
t-Bu DCE, 120 °C
Ph Ph Ph
78%

X. Li et al., Angew. Chem. Int. Ed., 55, 15351 (2016)

 Fukuyama Group - Group Meeting Problems
12/10/2016

O OEt
O
PPh3 (1.2 eq.) OEt
O EtOAc, 110 °C
O Ph
O Ph 72%

M. J. Krische et al., J. Am. Chem. Soc., 126, 4118 (2004)

2
O
OH
morpholine N
H O HFIP, rt; mCPBA O
N H
N N Ph
B(OH)2 , rt CHCl3, 0 °C
Ph

72% (syn:anti >95:5) 83%

A. K. Yudin et al., J. Org. Chem., 78, 11637 (2013)

A. K. Yudin et al., Org. Lett., 18, 6268 (2016)

3
1) OEt

OTMS
(3.3 eq.)
O O
CO2Me CO2Me 1) p-TsOH
ZnCl2 (2.5 eq.)
CuBr⋅Me2S (0.4 eq.) THF/H2O, rt
HMPA H 85%
CO2Me
O THF/Et2O, 0 °C to rt O 2) C=S(imid)2, DMAP
83% CHCl3, reflux
O 2) hν O 85% HO
hexane/CH2Cl2, rt 3) n-Bu3SnH, AIBN
98% benzene, 80 °C
87%, dr = 3:2

M. T. Crimmins et al., J. Am. Chem. Soc., 120, 1747 (1998)

 Fukuyama Group - Group Meeting Problems
12/24/2016

1
O2 O
Cs2CO3 (20 mol%)
O
O Ph O
+
N Ph Ph DMSO, 80 °C Ph
H N
H
72%

C. B. Miao et al., J. Org. Chem., 81, 12443 (2016)

O O O
Me SeO2
N
dioxane, reflux N

75%

C. M. Shafer and T. F. Molinski, J. Org. Chem., 61, 2044 (1996)

n-Bu Cr(CO)5(THF)
O (5 mol%)
Et3N n-Bu

THF, rt OH
95%

K. Ohe and S. Uemura et al., J. Am. Chem. Soc., 124, 526 (2002)
 Fukuyama Group - Group Meeting Problems
01/07/2017

TsN TsN
[Rh(CO)2Cl]2 (5 mol%)
O P(C6F5)3 (12 mol%) O

O 1,4-dioxane, 130 °C O N Me
Me sealed tube
N Me Me
O
72%

G. Dong et al., Tetrahedron, 71, 4478 (2015)

2
Me
AcO O
Ph3PAuNTf2 (5 mol%)
DCE, rt; Me
Ph
Tf2NH (5 mol%), rt
Ph Ph
61%
Ph

P. W. H. Chan et al., Org. Lett., 18, 5936 (2016)

3
Et CO2Et
CO2Et
BnNH2, SiO2
O
EtO2C
microwave (900 W) N
Et EtO2C Bn
77%

M. L. Rodriguez et al., J. Am. Chem. Soc., 126, 8390 (2004)

 Fukuyama Group - Group Meeting Problems
02/01/2017

1
O O N Ph
N Ph (AuCl)2dppm (5 mol%)

PhCl, 160 °C

90%

O. Miyata and M. Ueda et al., Angew. Chem. Int. Ed., 56, 2469 (2017)

2
N2
MeO
MeO P
O
Me CuI (10 mol%), K2CO3 Ph
PhCO2H (20 mol%)
+
TIPS H 1,4-dioxane, 100 ºC
TIPS
+ Me
70%
O (Z/E = 15:1)
J. Wang et al., Org. Lett., 18, 2024 (2016)
Ph H

Ti(Oi-Pr)3Cl
1-octene Mn(II) abietate (1 mol%)
O c-HexMgBr benzene, O2, rt; O
O H
OEt THF, rt KOH aq., rt n-Hex
H
HO2C
ND 85%
abietic acid

T. Lectka et al., Chem. Eur. J., 21, 8060 (2015)

O. G. Kulinkovich et al., Synthesis, 10, 1453 (2001)
 Fukuyama Group - Group Meeting Problems
03/04/2017

1
O
Dy(OTf)3 (0.05 mol%)
PhHN Me Me
O MeCN, 80 °C
OH
91% PhN

J. R. Alaniz et al., Angew. Chem. Int. Ed., 50, 7167 (2011)

NH

Ph NH2 MeO2C N Ph
CO2Me
Cl Et3N MeO2C
NH
CO2Me dioxane, rt 170 °C MeO2C
O
84% 84%

A. de Meijere et al., Org. Lett., 4, 839 (2002)

PhI(OAc)2 (2.0 eq.)* O

O TMSCN (3.0 eq.)* O
H BF3•OEt2 (4.0 eq.)
N
OH + H
CH2Cl2 rt N
rt; O
61% N
H
(1.0 eq.) (1.0 eq.)
* theoretically 1.0 eq.

Y. Hu et al., J. Org. Chem., 82, 1600 (2017)

 Fukuyama Group - Group Meeting Problems
03/08/2017

1
CO (1 atm)
Pd(OAc)2
1,10-phenanthroline

DMF, 110 °C
NO2 N
99% H

V. M. Dong et al., Tetrahedron, 65, 3062 (2009)

O O
O O
n-BuLi (3.5 eq.)
NHCOCCl3 NC
THF, –78 °C

Me 85% Me

T. Nishikawa et al., Org. Lett., 19, 380 (2017)

O O O
NO2 Cs2CO3 Cs2CO3 O
SO2Ph
O +
OH THF, rt; acetone, reflux O
SO2Ph evap.; HO O
52%

I. N. N. Namboothiri et al., Eur. J. Org. Chem., 20, 3316 (2016)

 Fukuyama Group - Group Meeting Problems
03/18/2017

1 O2, hν, Rose Bengal

MeOH, 0 °C;
O
Me2S, rt; Bn
BnNH2, rt; AlCl3 (0.2 eq) N
Me O acrolein CH2Cl2, rt
CH2Cl2, reflux
62%
72%

G. Vassilikogiannakis et al., Angew. Chem. Int. Ed., 56, 4020 (2017)

2
Me H H
Me
OH Me O
Ca(OH)2 H
+ O Me Me O
O EtOH, 80 °C
HO OH H O O
HO O
46%, d.r. = 3:1 H
Me

J. H. George et al., Angew. Chem. Int. Ed., Early View

doi: 10.1002/anie.201700114

3
1) NaH
n-BuLi (2.0 eq) MsO
Me
Cl THF DMF, 0 °C H
–78 to –40 °C; O Me
95%
Me O
O
Me CH3(CH2)4CHO 2) toluene, 90 °C
Me Cl –40 to 0 °C 85%, d.r. = 3:1 Me
78%

V. Tran and T. G. Minehan, Org. Lett., 13, 6588 (2011)

 Fukuyama Group - Group Meeting Problems
04/05/2017

1
MeHN C5H11 CO2Me
SO2 CO2Me
K2CO3 PhI(OCOCF3)2 Me N
+
DMF, 70 ºC CH2Cl2, rt
C5H11
NO2 81% 49% NO2

M. F. Greaney et al., Angew. Chem. Int. Ed., 56, 4183 (2017)

2
PhCHO
PhI(OAc)2 (0.5 eq.)
NH2 I2 (1.5 eq.) N
Ph
NH2 CH2Cl2, rt N
H
94%

M. Saha et al., Tetrahedron, 58, 1046 (2017)

3
BF4
N
N N Mes
Ar
Ar OH O
(20 mol%)
OH DABCO (1.2 eq) O
CHO nitrobenzene (2 eq)
n-Pr
O +
toluene, MS4A, rt O
N n-Pr N
Bn 77%, 95%ee, dr > 20:1 Bn

Ar = 3,5-bis(trifluoromethyl)phenyl

S. Ye et al., Chem. Sci., 8, 1936 (2017)

 Fukuyama Group - Group Meeting Problems
04/08/2017

1
MeO
KHMDS SPh
TMSCl, pyridine Me
OH
O THF/toluene MeOH
−78 to 60 ºC 40 ºC
SPh
O
57% 77%

T. Nishikawa et al., J. Org. Chem., 76, 6942 (2011)

2
Me
B

B Me
Me
O Me H (5 mol%) H
N N
+ +
N H Me THF, 60 ºC N

62%

H. A. Wegner et al., Org. Lett., 18, 1330 (2016)

i-Pr
OMe i-Pr
OMe Me3S(O)I H
CO2Et hν NaH
benzene DMF, rt MeO O CO2Et
MeO O O H
94% 88% OH
dr = 8:1

S. Ohta et al., Org. Biomol. Chem., 3, 2296 (2005)

 Fukuyama Group - Group Meeting Problems
04/19/2017

1 [Cp*Rh(MeCN)3](SbF6)2
O Ts (0.5 mol%) H
N NaOAc, AgOAc
O +
N H
H CH2Cl2, 60 ºC NTs
sealed tube O

82%

F. Glorius et al., Angew. Chem. Int. Ed., 56, 1381 (2017)

2
O O
N CN
Tf2O O O
PhO Cl DMAP CO2Me
N
N O
H ClCH2CH2Cl CH2Cl2 toluene N
MeO2C reflux 0 °C to reflux; 100 °C H O
TMSCN, rt O
66% 83%
68%

P. Magnus et al., Tetrahedron, 58, 3423 (2002)

3
O
Cl
Me N
Me O
H aq. H2SiF6
Me Me
TIPSO H Me
H Me MeCN, 65 °C
O Me Me
H
O N
H
J. L. Wood et al., J. Am. Chem. Soc., 130, 2087 (2008)
 Fukuyama Group - Group Meeting Problems
05/13/2017

1
O
OTf O SMe KF
+ NHPh
PhHN NHPh DMF, 90 ºC
TMS
O NPh
81%
M. Li et al., J. Org. Chem., 81, 5942 (2016)

2
O OH
HO 1) InCl3 (10 mol%) O O
MeCN, rt
HO N + N
2) Ac2O, DMAP AcO AcO
O O Me Me

H2N Me Me 93%, dr = 1:1 (2 steps) O Me O Me

J. S. Yadav et al., Tetrahedron Lett., 49, 3341 (2008)

3
O OH
MeO Hg lamp O
(medium pressure) H
N
MeCN N
O 76% O

K. I. Booker-Milburn et al., Org. Lett., 9, 4681 (2007)

4
SitBu2
(2.0 eq.)
SiOBntBu2
AgO2CCF3 (0.5 mol%)
Me
Me OBn benzene, rt
SiHtBu2
97%

P. A. Cleary and K. A. Woerpel, Org. Lett., 7, 5531 (2005)

 Fukuyama Group - Group Meeting Problems
05/24/2017

1
[RhCp*Cl2]2 (10 mol%)
AgSbF6 (10 mol%)
Cu(OAc)2 (20 mol%) O
OH PCy3 (10 mol%)
+ Ph Ph Ph
Ph CO2H toluene, 120 °C, air

65% Ph

G. Liu et al., Organometallics, 36, 1027 (2017)

2
1) toluene, reflux H
O 98% O
2) vinyllithium
THF, –78 °C to rt; H OH
OTMS sat. NaHCO3 aq., rt
69%

H. W. Moore et al., J. Org. Chem., 63, 6905 (1998)

3
PhI(OAc)2
N N NaN3 N N
CH3CN/H2O (9:1), rt CN
84%

A. H. Kalbandhe et al., Eur. J. Org. Chem.,1318 (2017)

 Fukuyama Group - Group Meeting Problems
06/03/2017

1
CHO
Ph
ZnEt2, ICH2Cl Ph O
OH Et2O, 0 ºC;
H Na2SO4
N
Ph Me Me Ph
CH2Cl2 n-BuLi N
Me THF, –30 ºC Me
98%
72%

V. K. Aggarwal et al., Org. Lett., 5, 1757 (2003)

2
Ms
Ph N Me
NO2 Hg(OTf)2 (10 mol%)
MS4A, DCE, rt;
NH
Ms O
Ph Ph N
Me Ph
rt O

93%
C. Y. Legault et al., Synthesis, 49 A (2017)

3 S
Ts
N N
H H
H
EDCI, i-Pr2NEt N NTs
N CHCl3, rt N
Bn Bn
72% H

J. S. Madalengoitia et al., Org. Lett., 6, 3409 (2004)

 Fukuyama Group - Group Meeting Problems
06/10/2017

1
1) TFA
O Boc CH2Cl2, rt O
90%
N N
OBoc
2) hν
benzene, rt
68%

J. Aube et al., J. Org. Chem., 68, 8065 (2003)

2
1) O

N SePh

O
Bu3P
OH THF, 0 °C Bu3SnH
81% AIBN
HN C16H21NSe N
2) NaNH2 (excess) toluene
liq. NH3 reflux Me
Br
86%
39%

M. Shipman et al., Tetrahedron, 58, 7165 (2002)

3
Ph
KOH·0.5H2O (1 eq)
O acetylene (14 atm)
O Me
Ph Me DMSO, 80 °C O

86% Ph

B. A. Trofimov et al., Eur. J. Org. Chem., 5142 (2009)

 Fukuyama Group - Group Meeting Problems
06/28/2017

1
CN O
NC [Rh(CO)2Cl]2 (10 mol%) NC
toluene, 150 ºC; CO (1 atm)
NC
p-xylene, 110 ºC
Br
NaH 52%
THF, rt

35%
S. K. Scott and A. J. Grenning, Angew. Chem. Int. Ed., 56, 8125 (2017)

2
NO2
NO2
H CuBr•SMe2 (5 mol%)
Et3N, H2O (6 eq.) O
N + TsN3
O MeCN, rt Ph N

Ph 76% HN
Ts
H
M. Terada et al., Org. Lett., 16, 5184 (2014)

3
O H
CO2Me AlCl3 O
CH2Cl2, rt
Me CO2Me
Me Me 75%
K. S. Shia and H. J. Liu et al., Org. Lett., 10, 121 (2008)

4 [Rh(COD)Cl]2 (2 mol%)
HO O DPEphos (4 mol%) O
O Ac2O (1.1 eq.)
O
+ Ph Me
Ph N Ph CH2Cl2, 60 °C Ph Ph
H (1.5 eq.) N Ph
quant.
PPh2 PPh2
O

B. Breit et al., Angew. Chem. Int. Ed., 56, 8422 (2017)

DPEphos DOI: 10.1002/anie.201704022
 Fukuyama Group - Group Meeting Problems
07/04/2017

1
[Rh(COD)Cl]2
DPEphos O O
O O Me Yb(OTf)3
+ Me OMe
Me OMe Ph DCE, 70 °C
Ph
93%
dr = 47:53

Q. Kang et al., Organometallics, 36, 2323 (2017)

2
O Me O Me O O Me
O O
TsOH
+
benzene, reflux
Me Dean-Stark trap Me Me
OH
Me Me Me Me Me Me
30% 15%

J. M. Amaro-Luis et al., Tetrahedron Lett., 57, 2713 (2016)

CHO H
BnNHOH AuCl3 (2 mol%) BnN
CO2Et CO2Et
CH2Cl2, rt CH3NO2, 70 ºC
CO2Et O CO2Et
92% 82%

S. Shin et al., Angew. Chem. Int. Ed., 47, 7040 (2008)

 Fukuyama Group - Group Meeting Problems
07/08/2017

1 OTMS
O2 BF3⋅Et2O
methylene blue CH(OMe)3
Me hν MgSO4
H
CH2Cl2, –78 ºC; TiCl4 CH2Cl2, 0 ºC;
Me
thiourea, rt Et2O, –78 ºC AcBr, rt
Me
O Me O
58% (2 steps) 57% Me Br OMe
Me O

P. S. Baran et al., J. Am. Chem. Soc., 138, 7536 (2016)

TMS
2 O Et2Zn H2O2
ligand NaHCO3 n-Hex OH
Si n-Hex HO
toluene, rt; MeOH/THF, reflux;
Me Me THF, 45 ºC K2CO3, rt Me

80% (2 steps)
Ph OH
dr > 98:2
HO Ph 86% ee
Ph OH Ph

N N

Me
ligand
I. Marek et al., Angew. Chem. Int. Ed., 52, 13717 (2013)

3
Ph RhBr3⋅2H2O (10 mol%) O
N dppp (20 mol%) N
NC O Ph
THF, 120 ºC
Me NC
65%

Ph2P PPh2

dppp

I. Nakamura et al., Chem. Eur. J., 23, 7686 (2017)

 Fukuyama Group - Group Meeting Problems
07/12/2017

1
1) DIBAL
CH2Cl2, –78 °C OH OH
N SiPhMe2 Cu(acac)2 88% H

N2 toluene, 85 °C 2) Hg(O2CCF3)2
AcOH, TFA N
O 58% CHCl3, rt;
AcOOH
0 °C to rt
81%

J. A. Vanecko and F. G. West, Org. Lett., 4, 2813 (2002)

2 1)
Br

CO2Me
LHMDS
THF, –78 ºC
55% HO
(E:Z = 4:1)
O CSA, LiCl H
OTBS (de > 98%) cyclic
S N
N Mes 2) benzene sulfoximine 1,4-dioxane, MeOH
40 ºC 90 ºC
88% MeO2C
80%

R. A. Stockman et al., Angew. Chem. Int. Ed., 55, 10047 (2016)

R. A. Stockman et al., Org. Lett., 16, 6290 (2014)

1) NaOH aq.
O EtOH, rt MeCHO O Me
60% SnCl4 (20 mol%)
O
2) t-BuOK, MeI CH2Cl2, 0 °C
t-BuOH, rt
80% 83% Me
(E:Z = <1:99)
(syn:anti = <1:99)

F. Shoenebeck et al., Angew. Chem. Int. Ed., 51, 5647 (2012)

P. Shanmugam et al., Tetrahedron, 52, 7737 (1996)
H. Saito et al., Bull. Chem. Soc. Jpn., 39, 694 (1966)
 Fukuyama Group - Group Meeting Problems
07/19/2017

1
TES TES
O O
O O TiCl4 O CHO
+
CH2Cl2, –78 ºC

60%

Y. Wu et al., Chem. Eur. J., 23, 2031 (2017)

2
1) THF, –78 °C to rt;
Me2TrocCl, –78 °C;
NaBPh4, –78 °C Bpin
NMe2
+ Bpin
Li 2) CDCl3, 50 ºC

67% (2 steps)

K. Aggarwal et al., J. Am. Chem. Soc., 139, 1790 (2017)

3
Me3S+I-, n-BuLi MeS CF3
O
(CF3CO)2O (2.0 eq.) THF, –20 ºC to rt;
Ph
C12H8O3NF3
N DCM, rt Ph N
AcOH, 80 ºC
Me CO2H
Me
92%
70%

T. Kurihara et al., Chem. Pharm. Bull., 49, 461 (2001)

M. Kawase et al., Tetrahedron Lett., 53, 2782 (2012)

4
Rh2(esp)2 (2.5 mol%)
OSO2NH2 PhI(OPiv)2 O
CaO, MS4A SO2
N
CH2Cl2, rt
Ph Ph
80%
Rh2(esp)2 : Bis[rhodium(α,α,α'‚α'-tetramethyl-1,3-benzenedipropionic acid)]
M. Shi et al., Org. Lett., 19, 3584 (2017)
 Fukuyama Group - Group Meeting Problems
08/01/2017

1
O Ph
PdCl2(CH3CN)2
Ph
TMSCl

1,4-dioxane, 70 °C

78%
R. A. Widenhoefer et al., Organometallics, 26, 4061 (2007)

2
Na CO2Et
NC S CN NaH
+ EtO2C SO2Ph NC CN
THF, −40 °C
NC CN
91% NC CN

T. Sakai et al., J. Org. Chem., 78, 10978 (2013)

3
TBSO O
O Rh2(oct)4 (2 mol%) TBSO N
N +
N CHCl3, MS4A, rt
Ph
N2 Ph N O O
81%

Rh2(oct)4 : Rhodium(II) octanoate dimer

M. P. Doyle et al., J. Am. Chem. Soc., 139, 9839 (2017)

 Fukuyama Group - Group Meeting Problems
08/23/2017

1
1) SOCl2, benzene;
O O allylamine, Et3N NC
hν, quant
carboxylic
H2O/acetone acid
Cl 2) PPh3, CCl4, Et3N
CH3CN
70% 80%

S. P. Chavan and T. Ravindranathan et al., Tetrahedron Lett., 37, 2629 (1996)

2
Pd(OAc)2 O
H H
N N NC Cs2CO3
+ NH
O DMF, 120 °C
I N N
H
71%

S. Sharma and A. Jain, Tetrahedron Lett., 55, 6051 (2014)

3 O
CO2Et

Et3N O
O Ac2O, rt; O
O
O HCl aq., 80 °C

O 20%

D. Didier et al., Org. Lett., 19, 2114 (2017)

 Fukuyama Group - Group Meeting Problems
09/06/2017

1
1) Oxone, NaHCO3
OBn 18-crown-6
acetone-CH2Cl2-H2O
[(JohnPhos)Au(MeCN)]SbF6 0 °C H
(2 mol%) 51% HO

CH2Cl2, rt 2) Li
ethylenediamine H
60% 50 °C OH
78%

A. M. Echavarren et al., Angew. Chem. Int. Ed., 53, 4896 (2014)

2
Cl

O O CN
K2CO3
O H
CN
ethylene glycol
Cl NH2 microwave
120 °C HN NH2
H
87% O N O
H

S. J. Tu and G. Li et al., J. Am. Chem. Soc., 131, 11660 (2009)

3
O
OEt
Ph O
O t-BuLi (4 eq) O
n-Bu n-Bu
OEt THF – 78 °C;
– 78 to 0 °C; HCl-EtOH
Br Br
reflux Ph
89%

M. Shindo et al., J. Am. Chem. Soc., 121, 6507 (1999)

 Fukuyama Group - Group Meeting Problems
09/27/2017

Me
1 OH
[IPrAuSbF6]•MeCN (5.0 mol%)
O
N i-PrOH, 60 °C
N
Me Me 89% Me
iPr iPr

N N
IPr = H. Ohno et al., Angew. Chem. Int. Ed., 54, 7862 (2015)
iPr iPr

2
PhO2SHN Ph
OH BF3•Et2O t-BuONa
H Ph + Ph NHSO2Ph Ph
N NC
Ph CH2Cl2, 0 °C CH2Cl2, 20 °C
Ph
65% 93%

Y. Wang et al., Org. Lett., 13, 3553 (2011)

3
Ph
O
NC Ag2CO3 (50 mol%)
Ph + O p-Tol
p-Tol CF3 MeCN, 110 °C N
NC N CF3
91%

X. Xu et al., Org. Lett., 19, 5292 (2017)

4 Pd(OAc)2 (5.0 mol%)

K2CO3 (1.0 eq.)
Ph NaBAr4 (10 mol%) O Ph
OH P(OPh)3 (10 mol%)
+ MeO
I DCE-H2O (50:1), 40 °C;
Cr(CO)5 TsOH, H2O, 50 °C O
(1.2 eq.) 80%
Ar = 3,5-bis(trifluoromethyl)phenyl
J. Wang et al., Angew. Chem. Int. Ed., 56, 13140 (2017)
 Fukuyama Group - Group Meeting Problems
10/04/2017

1
(Ph3P)AuCl (2 mol%) Ph
Ph AgOTf (2 mol%)

Ph MeNO2, rt

91%

M. Shi et al., J. Org. Chem., 73, 8344 (2008)

2
O

O
[(PhO)3P]AuCl
(10 mol%) Zn(OTf)2 H
O
AgSbF6 (10 mol%) (20 mol%) OH
+ Ph
DCE, 80 °C; DCE, reflux O
filt.; N
H OH
O 72%
N
R.-S. Liu et al., Angew. Chem. Int. Ed., 56, 12736 (2017)

3
[Rh(CO)2Cl]2 (2 mol%)
Cu(OPiv)2 (20 mol%) O
NMe2 dppb (5 mol%) Bu
PivOH (30 mol%) MeN
+ Bu Bu
PhCl, CO/O2 (2/1) Bu
130 °C

72%
N. Jiao et al., Chem. Sci., 8, 6266 (2017)
 Fukuyama Group - Group Meeting Problems
10/11/2017

1
Me Me
Me H t-BuOCl hν Me H
CH2Cl2, −78 °C; Et3N
Me H Me H
Me
N benzene N Me
H H
N C B N C
H , −78 °C 63% (brsm) H

(−)-hapalindole U (+)-ambiguine H
60%

P. S. Baran et al., Nature, 446, 404 (2007)

NO2 O
NHMe
+ EtO2C
O MeCN/H2O, 30 °C
N O N
Me EtO2C O
92%

N. Nishiwaki et al., Org. Biomol. Chem., 9, 2832 (2011)

3 O
EtO2C
NHn-Bu
O n-BuNH2, CAN
Ph + CO2Et
Me EtOH, MW
NO2 100 to 140 °C N
H Ph
85%

J. C. Menéndez and P. Merino et al., J. Org. Chem., 82, 7492 (2017)

 Fukuyama Group - Group Meeting Problems
11/04/2017

1
O
KH
O
THF, rt
OH
H O
42%

H. Heathcock et al., J. Org. Chem., 46, 9 (1981)

2
LHMDS 1) (BzO)2, K2HPO4
Et2O, –10 °C; DMF, rt
Ti(Oi-Pr)4, c-C5H9MgCl 73% N Ph
O Et2O,–78 to –40 °C; 2) NH2NH2, EtOH, rt O
(1S,2S)-Amine
Me
Ph H OLi (C19H23N) 3) (CH2O)n
Ph
toluene, MS4A Ph
50 to 120 °C
Me 51% (2 steps)
THF/Et2O, –78 °C to rt (dr ≥ 20:1, 93% ee)

72%
(dr ≥ 20:1, 95% ee)
(E:Z ≥ 20:1)
G. C. Micalizio et al., J. Am. Chem. Soc., 133, 9216 (2011)

3
S

N NH2
Cl
H
(10 mol%) O
Ph * NO2 DMAP (10 mol%)
O Me D N * O
+ D
S
Ph Me CHCl3, rt
(*: 13C) Ph Ph
O
83% (dr = 97:3)
(without D,13C-labeling)

W. -J. Xiao et al., J. Am. Chem. Soc., 130, 6946 (2008)

F. L. Gu et al., J. Org. Chem., 78, 12585 (2013)
 Fukuyama Group - Group Meeting Problems
11/08/2017

1
Me
Me 1) DMF, 60 °C
Me 78% N Ph
O +
Me N
2) air Me
N C O toluene, 120 °C
Ph Ph N
76%
Ph Me

D. L. Mo et al., Avd. Synth. Catal., 359, 3545 (2017)

2
O2 PMP
O N
H N CuCl2 (15 mol%)
N OEt
OEt + N
PMP O OEt toluene, 90 °C
Me O
Me O OEt
95%

Q. Wang et al., Org. Lett., 19, 6056 (2017)

3
1) AuCl[P(t-Bu)2(o-biphenyl)] (10 mol%)
AgSbF6 (5 mol%)
i-PrOH (1.1 eq)
Et3SiO MeNO2, 70 °C;
N3 O
SnCl4, rt N
2) OsO4 (5 mol%) O
NaIO4
THF-H2O (2:1), rt
71% (2 steps)
Y. H. Rhee et al., J. Org Chem., 79, 11119 (2014)

4
N2 [RuCl2(p-cymene)]2
Ph
(5 mol%)
PhS + OMe
Ph SPh
toluene, 60 to 80 °C MeO
O O
52%

J. Wang et al., Angew. Chem. Int. Ed., 46, 1905 (2007)

 Fukuyama Group - Group Meeting Problems
11/25/2017

Me
OH
N
Tf2O N
OMe O
O CH2Cl2, 0 °C;
evaporation O
OMe toluene, reflux

77% OMe

(Catalytic amount of water was contained.)

H. Nagase et al., Tetrahedron, 65, 4808 (2009)

1) MeO2C CO2Me
Me2N MeCN, rt CO2Me
S 52% CO2Me
N
2) MeCN, reflux
Me 90% Me2N N Me

M. Alajarín et al., J. Org. Chem., 71, 5328 (2006)

3
PhNC
IMes•HCl (15 mol%)
O K2CO3 (20 mol%) O NHPh

Ph DMA, 80 °C Ph

80%
H. Hong et al., Chem. Sci., 8, 2401 (2017)
 Fukuyama Group - Group Meeting Problems
01/06/2018

1
CuBr•Me2S (5 mol%)
ligand (10 mol%)
O (t-BuO)2 (3 eq.)
+ N N
O O N N
Ph H t-BuOH/DCE, 120 °C
Me Ph O
83% ligand

J. F. Soule et al., Org. Lett., 19, 6720 (2017)

1) [(C2H4)PtCl2]2 (3 mol%)
2 1-octene (10 mol%)
base (10 mol%)
Ph
Ph
toluene, 40 °C OH MeO2C
O CO2Me 98% Ph
+
O
2) neat, 200 °C
n-Pr H CO2Me
n-Pr
Me Et
34% 59%

t-Bu N t-Bu
base
E. M. Ferreira et al., J. Am. Chem. Soc., 138, 108 (2016)

TMS Ti(Oi-Pr)4, n-BuLi Me Ph Me Ph

toluene, −78 to 50 °C; TMS TMS
OH + OH
A, −78 °C to rt; Ph Ph
Ph MeOH, −78 °C H
Me

67% 17%
Ph dr = 10:1
A: Me
OPh
OLi
G. C. Micalizio et al., J. Am. Chem. Soc., 136, 8209 (2014)
 Fukuyama Group - Group Meeting Problems
02/21/2018

1
O O
Tf2O, 2-iodopyridine
Ph Ph
N N
CH2Cl2, 0 °C;
2,6-lutidine N-oxide, 0 °C; BnO2C CO2Bn
dibenzyl malonate, NaH
0 °C to rt

89%

N. Maulide et al., J. Am. Chem. Soc., 139, 16040 (2017)

2
Tol Cu(OAc)2 (1.1 eq) NH
O BOP (1.1 eq) Me
O S O DMAP (1.0 eq) Ph NH2 • HCl O
OH + N
MeNO2, reflux DMSO, reflux
OH N
Me Ph
80% 85%
N
N PF6
N
O P(NMe2)3 M.-Y. Chang et al., J. Org. Chem., 83, 2361 (2018)
BOP

3
OMe
Me MeO
N TBHP, Triton B
TfOH THF, rt;
MeO CH2Cl2, 0 °C SiO2, rt

97% 76% N
MeO Me
O
HO
O

S. E. Reisman et al., Angew. Chem. Int. Ed., 50, 9447 (2011)

4
OMe [RhCl(CO)2]2
OH OMe
(5 mol%)
CO (1 atm)
CHO
MeO
CO2Me DCE, 85 °C
CO2Me
OMe 86%

Z. Yang et al., Nat. Commun., 5, 5707 (2014)

 Fukuyama Group - Group Meeting Problems
03/10/2018

1
N2 O
OH (C6F5)3B
O CH2Cl2, −15 °C

88%

M. Brewer et al., Chem. Sci., 8, 6810 (2017)

2
Ot-Bu
Me
Me Ot-Bu Pb(OAc)4 (3.0 eq.) K2CO3 (5.6 eq.) Me O
HO Ot-Bu
O
MeCN, rt O MeOH-H2O, rt
HO OH
82% OAc OAc 92%

S. Arseniyadis et al., Tetrahedron, 52, 12443 (1996)

3
O Tf2O (2.0 eq) Me
pyridine (5.0 eq)
N N
CH2Cl2 toluene O
OH
−78 °C to rt O S
Me 130 °C CF3
75% 96%

A. Padwa et al., Org. Lett., 5, 189 (2003)

4
O
O O O
fac-Ir(ppy)3 (0.2 mol%)
+ N
O DMSO, rt
O O 5W blue LEDs

67%
K. Ueda
F. Glorius et al., Org. Lett., 20, 1546 (2018)
 Yokoshima Group - Group Meeting Problems
04/07/2018
1 HN
O
O
N
MeO2C NH N
H LHMDS (3.0 eq.), THF, –78 to 0 °C;
O H
OTBS BocHN
Boc N AcOH (1.0 eq.), –78 °C to rt H H
N F3C N OTBS
OTBS 74%
F3C O OTBS
O (without AcOH : 27-50%)

K. Namba et al., Nat. Commun., 6, 8731 (2015)

2 NC
m-CPBA (1.5 eq.)
I AcOH, 40 °C;
OH
NC I
(2 eq.)
OH
rt

55%
H. Yorimitsu et al., Angew. Chem. Int. Ed., 57, 4663 (2018)

Cl
3 N Mes
Mes N
OCOMe
(20 mol%) Me
O
Cs2CO3 (20 mol%)
Me O
Ph
THF, rt Ph
O O H
92% (dr > 20:1) Ph

X. Fang et al., Org. Lett., 20, 64 (2018)

4 Me Me
O
O O
O OMe
Me K2CO3 Me HO
OBz
MeOH, 65 °C H
O
O O Me
Me 60%
Me Me Me
Me
H. Ding et al., Angew. Chem. Int. Ed., 54, 6905 (2015)

5 O Me
Me
O O O
O2, hν
H H
CO2Me benzene, 0 °C N CO2Me
N
71%
OTBS O OTBS
O
A. Li et al., Nat. Chem., 5, 679 (2013)
 Yokoshima Group - Group Meeting Problems
04/28/2018
1
NTs NTs
N [Rh2(Adc)2] (0.01 eq.)
O Ph
N
CHCl3, 60 °C
O Ph H
92%

R. Sarpong et al., Angew. Chem. Int. Ed., 53, 9904 (2013)

2 1) A (1.4 eq.) O
SmI2 (3 eq.)
PhMe2Si OEt
H2O (8 eq.) B (4 eq.)
BnO LiBr (12 eq.) BnO O A
KH (5 eq.)
O THF, −78 to −30 °C TBAF (2 eq.)
N N
BnO BnO
2) Zn DMF, rt
Ph OOH
BnO AcOH. 80 °C BnO H OH
57% B
49% (2 steps)

P. Gilles and S. Py, Org. Lett., 14, 1042 (2012)

3
O O
OMe OH
hν O
Me Me
O
Me hexane, rt
Me Me
Me H O Me H
OH 90% Me O OMe

G. Majetich and J. Yu, Org. Lett., 10, 89 (2008)

4 OtBu

AdO (1.5 eq.)

ZnCl OAd
Pd(OAc)2 (0.05 eq.) N
Bs
I dpph (0.1 eq.) OBn OMe

MeO THF, rt toluene, 50 °C

N OH
Bs
80% 60% OBn

J. M. Ready et al., J. Am. Chem. Soc., 138, 10684 (2016)

 Yokoshima Group - Group Meeting Problems
05/12/2018
1 Ph
N O
Ph
O
HO BF3•Et2O (4.0 eq.) PPh3 (3.0 eq.)
N
O CH2Cl2, rt m-xylene, 130 °C
N N O Ph
Me 57% 74%
Me
The product was also obtained in refluxing 1,2-dichlorobenzene for 6 h even in the absence of PPh3
in the seond step. Different mechanisms were proposed. Please answer each mechanisms.

J. N. Kim et al., Tetrahedron Lett., 59, 1484 (2018)

2 H
H Br2 H
OMe hν CH2Cl2, 0 ºC;
H + H O
pentane evaporation;
MeO
OMe nBu3SnH
65%
59%

P. A. Wender and J. J. Howbert, J. Am. Chem. Soc., 103, 688 (1981)

3 O
Rh2(OAc)4 (cat.) O
Ph N3 Ph
+ N
EtO2C CH2Cl2, rt CO2Et
N2 (2.0 eq.) 71%

S. Katukojvala and V. Kanchupalli, Angew. Chem. Int. Ed., 57, 1 (2018)

4 N
Ph
10% KOH aq., rt; Ph
N
4 M HCl aq.
rt to 90 °C O
O
NO2
83%

H. E. Zimmerman et al., Helv. Chim. Acta, 84, 1342 (2001)

5 CO2H
O3, CH2Cl2, –78 ºC;
OH +
Me2S, –78 ºC to rt;
O
water (quench) OH
O
74% (ca. 4/1)

A. G. Martinez et al., Tetrahedron Lett., 46, 5157 (2005)

 Yokoshima Group - Group Meeting Problems
05/19/2018
1) m-CPBA (2.5 eq.)
1 N3
CHCl3, rt
O
2) Pd/C, H2, Ac2O NAc
O Et EtOAc, rt
N Et
3) TFA
CH2Cl2, rt
30% (3 steps) O
N
H
M. Dai et al., Org. Lett., 16, 6216 (2014)

LDA
2 THF, –78 to 0 °C;
OH
B Ph
OH
ZnCl2•TMEDA
N
rt; Me

Br S Br PdCl2(dppf)•CH2Cl2
Pd(PPh3)4 (5.0 mol%) S
I (5.0 mol%)
t-Bu3P•HBF4 Me
NHPh (20 mol%)
60 °C NaOt-Bu, K3PO4
1,4-dioxane, 125 °C
69%
57% A. Mori et al., Org. Lett., 20, 958 (2018)

Ph
3 AcO Ph3PAuCl (5 mol%) O
AgSbF6 (10 mol%)
H Ph O
BnO
O CH2Cl2, rt
OBn
BnO 80%

X.-W. Liu et al., Chem. Sci., 8, 6656 (2017)

4 1) TsCl, Et3N
CH2Cl2, rt
83%
2) 4-ethyl-4-pentenoic acid O
O EDCI, DMAP
H
N CO2Me CH2Cl2, rt N
N N 87%
H H
O Me
3) o-dichlorobenzene O
N reflux N
Me 74% Me
CO2Me

D. L. Boger et al., Org. Lett., 7, 741 (2005)

OH
5
I H
Pd(OAc)2 O
DEAD K2CO3, Bu4NCl

CH2Cl2, 0 ºC DMF, 80 ºC H
N N CO2Et
quant. 63% EtO2C H

K. V. Radhakrishnan et al., J. Am. Chem. Soc., 131, 5042 (2009)

 Yokoshima Group - Group Meeting Problems
05/26/2018
1 Me
IrCl(CO)(PPh3)2 (1 mol%)
TMDS (2 eq.) N N
O toluene, rt;
N Me Me
+
SiO2
−78 °C to rt N CO2Me N CO2Me
Me Me
N CO2Me
Me major minor
52% 31%
*TMDS = 1,1,3,3-Tetramethyldisiloxane

D. J. Dixon et al., Angew. Chem. Int. Ed., 55, 13436 (2016)

Br
NH2OH•HCl (1.2 eq.) Me A H
O H2O, rt; KHCO3 N Me
A Me O
O
HO NaHCO3 (2.5 eq.), rt; EtOAc, rt
Me
Br2 (1.7 eq.)∗, CH2Cl2, 0 ºC O Me
91% O Me
∗theoretically 2.0 eq.

D. Y.-K. Chen et al., Angew. Chem. Int. Ed., 56, 12277 (2017)
E. M. Carreira et al., Angew. Chem. Int. Ed., 54, 11227 (2015)

3 CF3
Me
OH
AgSbF6 (50 mol%) Me
A (10 mol%) CF3
H2O (1.1 eq.) O O O O
O P
O DCE, rt O O OH
Me O Me O
CF3
92%
Me
Me O A
CF3

T. Wang and D. Z. Wang et al., Org. Lett., 15, 2362 (2013)

4
SiMe2Ph Et3N (3 eq.)
Me nBu
nBu (5 eq.) H
Cl
TFE/Et2O Cl
Cl
−78 ºC to rt O
O
42%

P. R. Schreiner et al., Angew. Chem. Int. Ed., 47, 8696 (2008)

 Yokoshima Group - Group Meeting Problems
06/02/2018
1 H OH
1) VO(acac)2, t-BuOOH H OH
CH2Cl2, MS4A, 0 °C to rt K2CO3 (15 eq.)
OO
H 2) Et3N, SiO2 DMF, MS4A
O O 75 °C H
O CH2Cl2, rt
OH
O
93% (2 steps) 68%

J. D. Winkler et al., Org. Lett., 5, 1805 (2003)

2
OH
O2N MeO2C CO2Me N
Zn powder (20 eq.)
NC +
n-Pr NH4Cl aq., MeOH, rt
n-Pr n-Pr
MeO2C CO2Me MeO2C CO2Me
pH A (%) B (%)
4.5 45 18
5.7 18 27

A. Kamimura et al., Tetrahedron Lett., 54, 1842 (2013)

3
H H Pd(OAc)2 (10 mol%)
N N HN
PhI(OAc)2 (3 eq.) O
O N
EtOAc, 25 °C OAc

71%
H

L. Tao and M. Shi, Org. Lett., 20, 3017 (2018)

4
PBu3 (10 mol%)
(9-BBN-H)2 (0.48 eq) EtO2C Ph (0.95 eq)
O
EtO B
Ph
THF, 60 °C; 80 °C
Ph
95% Ph

M. Sawamura et al., J. Am. Chem. Soc., 136, 10605 (2014)

5
Ph Ph 1) NIS (2.5 eq) 3) NaClO2, 2-methyl-2-butene
MeCN-H2O NaH2PO4, t-BuOH-H2O
0 °C, 62% rt, 92% O O
O O I
2) DDQ 4) CAN, MeCN-H2O, rt;
MeCN-H2O K2CO3, rt, 80% O
60 °C, 58%

Y. Kita et al., Angew. Chem. Int. Ed., 44, 734 (2005)

 Yokoshima Group - Group Meeting Problems
06/09/2018
1
HO O HO O
Boc LHMDS TESOTf (0.3 eq.) H Boc H Boc
O
N THF, −78 °C; CH2Cl2, −78 °C;
N N
O TESCl, rt Et3N•3HF, rt
TBDPSO
76% 51% TBDPSO TBDPSO
1 : 5

P. Chiu et al., Angew. Chem. Int. Ed., 57, 5253 (2018)

2 1) Br2HC
O Me3Si
Br2HC
OH
Et2Zn F3CCOMe Me3SiOTf HO
O O Na
O
toluene, rt Oxone 2,6-lutidine N
NCO2Me MeO2CN N
HO
2) Zn/Cu, NH4Cl Na2EDTA aq. CH2Cl2, rt O O Na
MeOH, 0 °C MeCN, 0 °C O
80% O Na2EDTA
36% (2 steps) 87%

M. Dekhane et al., Org. Lett., 12, 2834 (2010)

3 [IrCp*Cl2]2 (2.0 mol%)

N2 AgNTf2 (8.0 mol%)
O O O NaOAc (1.0 eq.) K2CO3
+ O
N O O 1,2-DCE, 70 °C MeOH, rt N
H H
90%
91%

P. Patel and G. Borah, Chem. Commun., 53, 443 (2017)

4
O Et3N OH
OH microwave O
toluene, 220 °C
in sealed tube

87%

J. M. Warrington and L. Barriauly, Org. Lett., 7, 4589 (2005)

5 Me
O
Boc2O Boc
H O HN N
Me N O 70% HClO4 Et3N
+
O H2O/1,4-dioxane THF, 60 °C
105 °C H
H
65% (2 steps) Me
NH2

R. Sarpong et al., J. Am. Chem. Soc., 132, 5926 (2010)

 Yokoshima Group - Group Meeting Problems
06/16/2018

OH Me 1) Pb(OAc)4 H O
AcOH K2CO3 NaIO4, HCl aq.

2) xylenes EtOH THF, (pH 4)

HO2C
reflux Me
22% (2 steps)

P. Yates and T. S. Macas, Can. J. Chem., 66, 1 (1988)

2
1) t-BuOK (0.1 eq.)
THF, 70 °C
t-BuLi (2.4 eq.) 2) t-BuOK, TBSCl, LDA
LaCl3•2LiCl (1.3 eq.) NH2
THF, rt to –50 °C
Boc C20H30N2O5
N Et2O, –40 to –70 °C; 3) TFA/DCM = 1/10
H N
O 0 °C H
68% (3 steps)
NBoc
, –70 °C to rt

75%

K. C. Nicolaou et al., Angew. Chem. Int. Ed., 47, 4217 (2008)

H Dy(OTf)3 (5.0 mol%)

N
O MeCN, 80 °C N
OH
96%

L. Palmer and J. Read de Alaniz, Angew. Chem. Int. Ed., 50, 7167 (2011)
 Yokoshima Group - Group Meeting Problems
06/23/2018
Me
1
TMS O
TMS Me
Me Me Me
Me Me

O
1,2-DCE, 100 °C
N sealed tube N
Ts Ts Me
89%

Y. R. Hoye and T. Wang, J. Am. Chem. Soc., 138, 13870 (2016)

2
1) nBu3SnH (1.2 eq.), AIBN (cat.) OH Me
Br Tl(ONO2)3 (2 eq.) benzene, 80 °C
S S
TMS MeOH, Celite, −15 °C 2) TBAF
H
THF
66%
81% (2 steps)

Y.-M. Tsai et al., Tetrahedron Lett., 34, 1303 (1993)

3 O
O CO2H
CuBr2 (20 mol%), O2
NaOMe (2 eq.) O

NH DMF, MS3A, 150 °C O

N
Me 84% Me

F. Zhang et al., Org. Lett., 19, 3418 (2017)

4
[Ru(bpy)3]Cl2·6H2O (1 mol%) Me O
KH2PO4 (1 eq.), hν (14 W CFL) Me
NH O OMe
N
O2, MeOH, rt H
Me Me O
69%

bpy:2,2'-bipyridine, CFL:Compact Fluorescent Light

Mechanistic studies suggest generation of 1O2 in situ.
W. Fan and P. Li, Angew. Chem. Int. Ed., 53, 12201 (2014)

5
1) NaOH, RMe3NCl
nC CHCl3-H2O, 80 °C, 58%
11H23 2) conc.HCl-MeOH, rt, 89% nC
O 11H23
HO
O 3) K2CO3, MeOH, rt, 77% O
4) NaBH4, MeOH, rt, 84%

(R = C16H33)

Y. Masaki et al., Chem. Pharm. Bull., 52, 848 (2004)

 Yokoshima Group - Group Meeting Problems
06/30/2018
1
CO2Et [RhCp*Cl2]2 (2.5 mol%) O
KF (2.0 eq.)
+
O
OMe DME, 100 °C
O N OH O N
H 87% H

X. Fan et al., Adv. Synth. Catal., 360, 1 (2018)

2
BocN N
Grubbs 2nd
DCM, rt; NaBH4
O A and B MeO
TFA, rt; Et2O/DCM/H2O H
O
O H aq. Na2CO3, rt rt
HCl H
Et2O/DCM, rt; OH
OMe 65% (2 steps)
aq. NaOH, rt;

M. D. Smith et al., Angew. Chem. Int. Ed., 55, 14306 (2016)

3
NHTs Me
N
NaH H
OTBDPS Me
Me
• toluene
Me reflux
Me Me
Me OTBDPS
Me 87%

H.-Y. Lee et al., J. Am. Chem. Soc., 136, 10274 (2014)

4
TBDPSO O O 1) Rh2(OAc)4 O
benzene, reflux
MPMO 90% TBDPSO
OMe
N2 2) DBU
toluene, 70 °C O OMPM
OTBDPS 89% OMe
3) diphenyl ether, 180 °C
58%
K. Iguchi et al., Org. Lett., 8, 4883 (2006)

5
OMe H H H H H
PtCl2 (5 mol%) H
H + H
H toluene, 80 °C H
MeO
OMe
56% (Z/E = 2 : 1) 15%

C. D. Vanderwal et al., Angew. Chem. Int. Ed., 51, 7572 (2012)

 Yokoshima Group - Group Meeting Problems
07/07/2018
1
1) Cl3CCN (excess) 3) mCPBA (1.05 eq.) O
DBU (1 eq.) CH2Cl2, −20 °C
OH HN CCl3
CH2Cl2, −20 °C to rt 97%
PhS
2) Na2CO3 (2 eq.) 4) P(OMe)3 (excess)
OH o-xylene, 140 °C OH HN CCl3
MeOH, reflux
in a sealed tube O
58% (2 steps)
(crude, dr = 1:1)

N. Chida et al., Org. Lett., 11, 2687 (2009)

2
(TMS)3SiH
O AIBN
O HO O O
O benzene, reflux;
Si MeLi, 0 °C TMS
Br
92%

L. Fensterbank et al., Tetrahedron, 52, 11405 (1996)

3
Ph
Ph O
C
CO2Et toluene, reflux
N + + O
• 61% O N
EtO

J. Li et al., Org. Lett., 16, 5604 (2014)

4
1) PhNCO Cl2Ce
NO2 Et3N O
HO
OTMS benzene, rt BF3⋅Et2O CF3CO2H
O
2) HCl in MeOH THF, −78 °C MeCN, 80 °C
O DCM, rt N
H
68% 67%
75% (2 steps)
(dr = 4:1)

S. Diethelm and E. M. Carreira, J. Am. Chem. Soc., 137, 6084 (2015)

 Yokoshima Group - Group Meeting Problems
07/14/2018
1 O
(EtO)2P CN
Hex
O 1) Br2
CH2Cl2, 0 °C N-O acetal t-BuOK
CN
Hex (C19H24BrNO3)
Br N 2) DMF O
Ac HO −78 °C to rt Br N
MS4A H
MeCN-DMF, rt 70% (98%ee)

50% (2 steps)

T. Kawasaki et al., Chem. Commun., 420 (2006)

2 N
S
N
O O 1) TMP, n-BuLi 3) N N
, DMAP
t-BuOMe, 0 °C to rt DCM, 0 °C to rt
90% 84% O
Me H
2) 6.0 M HCl 4) P(OMe)3, reflux
O THF, 50 °C 88% H
77%
OMOM

B. Liu et al., Org. Lett., 13, 5406 (2011)

3
CO2Et
CO2Et Cs2CO3
N
Br DMF, 80 °C Me
N
77%

J. Chang et al., J. Org. Chem., 82, 7045 (2017)

4
O O
I2 (50 mol%) S
+ NaNO2 Me
Me (1.2 eq)
DMSO, 90 °C N
Br Br OH
76%
Radical quenchers almost inhibit this reaction.

S. Batra et al., Org. Lett., 18, 4190 (2016)

5 O
CuCN Me3Al (2 eq)
Me BF3•OEt2 OH
THF, 0 °C; CH2I2 (2 eq)
Ph Si Li
allene, –40 °C; –40 to 0 °C CH2Cl2
Me
–60 °C to rt

58% (2 steps)

F. J. Pulido et al., J. Am. Chem. Soc., 127, 8022 (2005)

 Yokoshima Group - Group Meeting Problems
07/28/2018
1
O 1) Zn
N CO2i-Pr O
AcOH-H2O (4:1) i-PrO2C N
O 15 °C PPh3 O
N H
H 2) NH3 aq. THF
O CHCl3, rt 0 °C to rt
O N
Cl3C 51% (2 steps)
87%

S. Jiang et al., Chem. Commun., 50, 9284 (2014)

2 O
N
Me

NHBoc
N OH
O TBA
H
(15 mol%)
+ NBoc
SMe Et2O, –50 °C; N
N NaBH4, CeCl3·7H2O SMe
PMB
PMB MeOH, –50 °C

87% (96% ee)

D. W. C. MacMillan et al., J. Am. Chem. Soc., 131, 13606 (2009)

3 Me
O O O
Me CO2Me hv (310 nm) BBr3
Me
Me solid state, 0 °C CH2Cl2, 0 °C Me
OMe Me
76%

M. A. Garcia-Garibay et al., Org. Lett., 6, 645 (2004)

4
Me Me
1) t-BuOOH
VO(acac)2 OH
benzene, rt TiCl4
OH
N3 2) TMSCl CH2Cl2
imidazole N
–78 °C to 0 °C
DMF, rt
66% (2 steps) O
68%
C. Fan et al., Org. Lett., 10, 1763 (2008)

5 OMe

HO Me Ph OMe OH
TsOH H3PO4
two tricyclic compounds
(one is an eimer of the other.) Ph Me
CH2Cl2, rt CH2Cl2, rt
H O
OH
Me 86% 93%

R. Sarpong et al., J. Am. Chem. Soc., 140, 9291(2018)

 Yokoshima Group - Group Meeting Problems
08/04/2018
1 Me Me
H
N

N LDA (1.05 eq.) Me

THF, rt

50% O
Br O O
O

L. Mark et al., J. Am. Chem. Soc., 134, 15572 (2012)

2
1) NH2OH•HCl
BnO NaHCO3 Ti(Oi-Pr)4 (1.1 eq.) BnO H
O 91% EtMgBr (2.2 eq.) N
OH
2) MsCl (2 eq.) −78 °C to rt;
BnO OBn pyridine BF3•OEt2, rt BnO OBn
76%
42%

P. Bertus and J. Szymoniak, Synlett, 9, 1346 (2007)

3
O
O Tf2O (1.5 eq.) n-Bu
pyridine (3.0 eq.) N
BocHN n-Bu HN
N
H DCM O
Ph 4 to 25 °C
Ph
83%

Z. Pan et al., Org. Lett., 16, 5902 (2014)

4

OBn OBn PhSeSePh OBn OBn

SPh2•BF4 mCPBA
KOH NaBH4 pyridine
N3 DMSO, rt EtOH, rt n-hexane-DCM N3
OMe OMe
−30 °C to rt O
O
57% (3 steps)

Y. Q. Tu et al., Org. Lett., 14, 3604 (2012)

 Yokoshima Group - Group Meeting Problems
08/18/2018
1 Ph
OEt OH
[RuCl2(p-cymene)]2 (0.5 mol%) p-TsOH (cat.) O
t-BuCO2H Ph
toluene, 0 to 40 ºC CH2Cl2, rt O t-Bu

80% 80%

Y. Kita et al., J. Chem. Soc., Perkin Trans. 1, 2999 (1993)

2 TBSO OTBS

OAc TBSO OTBS

(1.5 eq.) t-Bu SbF6
t-Bu
A solution (cat.) P Au NCMe
H
CH2Cl2

48-55% A solution
OAc

A. M. Echavarren et al., Angew. Chem. Int. Ed., 52, 6396 (2013)

3 Me
OH O
N TMS CsF (3.0 eq.)
+ Me
Me N
OTf MeCN, 80 °C
Me 96%
2.2 eq.

T. Yao et al., Org. Lett., 19, 3135 (2017)

4 Ph Ph
HO MeO
MeO (1.0 eq.) O
BF3·OEt2 (3.0 eq.) H
MeO
MeO CHO H
CH2Cl2, rt
3.0 eq.
86% OMe
MeO

S. Nagumo et al., J. Org. Ch., 83, 9103 (2018)

5 MeO B
O
O i-Pr
N N
i-Pr

i-Pr i-Pr
[RhCl(C2H4)2]2 (3.0 mol%)
dppf (6.0 mol%) (10 mol%)
Et3N, H2O Ni(cod)2 (5.0 mol%)
OBn dioxane, 100 ºC toluene, 70 ºC OBn
OBn OBn
81% 90%
M. Murakami et al., J. Am. Chem. Soc., 128, 2516 (2006)
 Yokoshima Group - Group Meeting Problems
08/25/2018
1 Li•(+)sp
O
CbO PMP Cb =
SePh MeOTf Ni-Pr2
Et2O, –78 °C; CH2Cl2, rt; Ph
Ph • PMP
B(pin) H
MgBr2 NaHCO3 H (+)sp =
H MeOH, 40 °C MeOH, rt N N

91% (99:1 e.r.) 83% (98:2 e.r.)

V. K. Aggarwal et al., Angew. Chem. Int. Ed., 57, 8203 (2018)

2 O
Me

P CO2Me
OTBDMS CF3CH2O
CF3CH2O tBu N tBu CHO
OHC
KHMDS, 18-crown-6 Tf2O
MeO2C
THF, –78 °C to rt CD2Cl2, rt; N
iPr2NEt, rt NC
OHC N CN >39%
44%
D. Nakajima
G. Bélanger et al., Org. Lett., 13, 6204 (2011)

3 NH2
O O3 O
CO2Me AcOH-H3PO4 (1:1) CH2Cl2, –78 °C; KOH
O
toluene, reflux Me2S, –78 °C to rt CH2Cl2, rt
N
85% 84% 90%

X. She et al., Org. Lett., 18, 4682 (2016)

4 O
H Me
Me Cp2TiCl O
NBS
A+B + O
(A:B = 3:2) CDCl3, rt O
O THF, rt
H Me Me O Me
Me diastereomers
68%
86% from A 90% from B

R. Sarpong et al., J. Am. Chem. Soc., 137, 6327 (2015)

5 1)
1) TFA, CH2Cl, 0 ºC
O CN CO2Bn 2) cyclopentadiene O
BocHN CHCl3, rt HCHO, H2O, rt MeHN
SH protected dipeptide N CO2Bn
2) n-Bu3SnH (2.5 eq.) 3) Et3SiH, TFA Me
AIBN (1.0 eq.) CHCl3, rt
toluene, 100 ºC
52% (3 steps)
62% (2 steps)
S. J. Danishefsky et al., J. Am. Chem. Soc., 132, 4098 (2010)
 Yokoshima Group - Group Meeting Problems
09/01/2018
1 MgBr
BnO
C6H13 HCO2H K2CO3 N
BnO Boc H
N O
Boc THF, 0 ºC toluene-THF MeOH-H2O HO
0 ºC rt
79% C6H13
88% 98%

C. Kibayashi et al., Angew. Chem. Int. Ed., 41, 3017 (2002)

2 O
Ph (1.2 eq.) Ph
Ph
I2 (1.5 eq.)

THF, rt
O
94% Ph O

N. T. Patil et al., Eur. J. Org. Chem., 5178 (2009)

3 1) Tf2O
BrMg
CH2Cl2, −50 ºC
CeCl3 65% CH2OH

O Br THF 2) LAH
OMe 98%
76%

M. Harmata et al., Tetrahedron Lett., 43, 2347 (2002)

4 O2 (1 atm)
CuBr2 (25 mol%)
OMe
Cy TMEDA (50 mol%)
N
MeO
Cy MeOH-MeCN (1:4)
NCy2
40 °C

66%

J.-S. Tian and T.-P. Loh, Angew. Chem. Int. Ed., 49, 8417 (2010)

5 OCO2Me (2.0 eq.)

TMSN3 (2.0 eq.)

TMS Pd2(dba)3•CHCl3 (2.5 mol%)
P(2-furyl)3 (10 mol%) MeMgBr (4.0 eq.)

toluene THF N TMS

NC 100 ºC 0 °C to rt H

59% 93%

Y. Yamamoto et al., J. Am. Chem. Soc., 124, 11940 (2002)

 Yokoshima Group - Group Meeting Problems
09/08/2018
1)
1 NH

Me2N NMe2
OH CO2H O MeOH, −7 °C; O
O O PhI(OAc)2 (2.4 eq.)
(EtCO)2O O
Me Me −7 °C, 65% O
Me OMe
180 °C 2) ethylene (70 bar) O
toluene, 140 °C
82% 90% (dr = 6:1) Me Me OMe
Me Me

R. Sarpong et al., J. Am. Chem. Soc., 139, 11349 (2017)

2 BF4
Boc
Cl N O BocNHOH N Boc
(1.2 eq.) n-Bu4NIO4 O N
OBz
+ O
OBz MeCN, rt; CH2Cl2, rt OBz
DBU, rt OBz OBz
60% OBz
79% A:B = 9:1 A B
Y. Iwabuchi et al., Angew. Chem. Int. Ed., 55, 13189 (2016)
3
S
O
H
HBF4 MeO2C
MeO2C
DCM, 0 °C MeO2C
MeO2C OMe S
H
77%
OMe
C. Saa et al., Angew. Chem. Int. Ed., 51, 12316 (2012)

4 O

HO OH BF3•Et2O H Me
O O
MsCl Ca(OH)2
Me
Me
DMF MeOH, rt
OH O rt to 90 ºC OH O
40%
90%
Z. W. Shen et al., Eur. J. Org. Chem., 1356 (2013)

5 Cl Me O
N Cu(OAc)2 (cat.), (O2)
N Cl N N Me
N O AcOH/H2O/DMF
H N
Et 80 °C H Et O

71%

L. El Kaim and L. Grimaud et al., Eur. J. Org. Chem., 3117 (2011)

 Yokoshima Group - Group Meeting Problems
09/15/2018
1 CN

N
Hg(NO3)2, H
CH2Cl2
–40 ºC to rt; HCl aq. NH

NaBH4 reflux H
N
MeOH, rt
53%
39%
D. Stoermer and H. Heathcock, J. Org. Chem., 58, 564 (1993)
2
1) (COCl)2, DMSO
O Et3N O
Me O Bu3SnH CH2Cl2, –78 °C
AIBN O
OH 80% O
IR: 1782, 1732 H
TBDPSO OH Me O
O benzene 2) NaBH4
80 °C MeOH, –78 °C Me OH
Me O SePh 3) TsOH TBDPSO
40% toluene, 80 °C
83% (2 steps)

G. C. Micalizio et al., J. Am. Chem. Soc., 138, 1150 (2016)

3 O
HO H
H
H O
I2 (cat.) O N
O H H
TBSO H N MeOH, rt

84% HO
OH

P. D. Brown and A. L. Lawrence, Org. Biomol. Chem., Advance Article

DOI: 10.1039/c8ob00702k
4 1) bromoform
LDA
Br THF
A
Me 2) n-BuLi (2 eq.)
Et2O
−78 to −20 ºC

1) Me2C=C(NMe2)Cl
CH2Cl2, rt;
O MeONHMe•HCl Me O
Me HO H
2 ºC to rt
85% Me
Me O
O
2) A Me Me
O Me H O
Et2O
Me −75 ºC to rt Me
68%
B. Wickberg et al., J. Chem. Soc., Chem. Commun., 865 (1990)
 Yokoshima Group - Group Meeting Problems
09/29/2018

1 1) LHMDS TIPSO TIPSO

O CF3CO2CH2CF3 OTBS
OTBS
THF, –78 °C hν

2) MsN3, Et3N benzene, rt OH

MeCN/H2O, 25 °C
64%
82% (2 steps)

R. L. Danheiser et al., J. Org. Chem., 60, 8341 (1995)

2 1) BF3•OEt2
CH2Cl2, −20 °C formalin
O NBn 97% Et3N O
O O H
H MeOH, 23 °C;
O 2) H2, Pd/C
HCl-MeOH HCl-MeOH, 23 °C O
96% N H
67%

L. E. Overman et al., J. Org. Chem., 56, 5005 (1991)

3 Ph
CO2Me

CO2allyl 1) Pd2(dba)3 (0.06 eq.)

Yb(OTf)3 (0.1 eq.) MeCN, reflux Ph
O MS4A 66% Ph N
+ PhNHOH Ph
Ph toluene, rt 2) DBU (3 eq.)
MeCN, rt MeO2C
91% 88%

M. A. Kerr et al., Angew. Chem. Int. Ed., 51, 11088 (2012)

4
NO2

(EtO)2(O)P

Ot-Bu O2N
Ot-Bu H
mCPBA Al2O3 LHMDS
H
THF, −10 °C

71%

S. J. Danishefsky et al., J. Am. Chem. Soc., 124, 9812 (2002)

 Yokoshima Group - Group Meeting Problems
10/06/2018
1
1) LHMDS, hexane, –10 °C;
CH2=C(Me)CO2Me 1) K2CO3
MeOH, rt, 90% O
O –10 °C to rt, 70%
C15H22O5
2) O3, CH2Cl2-MeOH, –70 °C; 2) p-TsOH·H2O
Ac2O, Et3N, DMAP benzene, reflux, 65% CO2Me
benzene, reflux, 60%

A. Srikrishna et al., Tetrahedron Lett., 47, 363 (2006)

2
MeO2C Me BF4
S Me
MeO2C
Me S (1.0eq.)
O H
CH3CN, −40 °C;
OAc O O
MeS Et3N, −40 °C MeS N
N O
MeS 80%
dr = 1:1

J. D. Ginn and A. Padwa, Org. Lett., 4, 1515 (2002)

3
∗IPrAuNTf2 (5 mol%)
CH2Cl2, rt; O *IPr =
Ph O concentration; i-Pr i-Pr
+ OEt Ph
Me N N
TsOH (20 mol%) HO Me
acetone-H2O (2mM), rt
i-Pr i-Pr
93%

L. Zhang et al., J. Am. Chem. Soc., 130, 6944 (2008)

4
O O O
SeO2 (2.2 eq.)
Me
N 1,4-dioxane, reflux N

75%

C. M. Shafer and T. F. Molinski, J. Org. Chem., 61, 2044 (1996)

 Yokoshima Group - Group Meeting Problems
10/20/2018

1
MeO2C
CO2Me Ts EtO2C Ts
N microwave microwave N
O N O
PhCF3, 250 °C PhCF3, 200 °C
N
Me in sealed tube in sealed tube Me
EtO2C
99% 99%

C. Meyer and J. Cossy et al., Angew. Chem. Int. Ed., 53, 8705 (2014)

2
LDA (4.0 eq.)
THF, −78 °C to rt; O
O TMSCl (1.2 eq.) 0 °C to rt;
Ph
O NEt2 MeI (1.2 eq.) (scavenger for LDA)
PhCHO (1.3 eq.), rt OH
57%

R. J. Chein et al., Org. Lett., 20, 5362 (2018)

3
S O
hυ NMe
Et2N S NMe PhLi
hexane, reflux Ph2O, reflux O
THF, 0 °C;
NaOH aq., rt Ph
74%* 89%
66%
*mixture of two stereoisomers

R. S. Grainger et al., J. Org. Chem., 73, 8116 (2008)

4
3) TsCl, Et3N Ts
1) NaN3, NH4Cl 51% (3 steps) N
O
2) PPh3 4) BF3•OEt2
SO2Ph SO2Ph
76%

C. M. G. Löfström and J-E. Bäckvall, Tetrahedron Lett., 37, 3371 (1996)

 Yokoshima Group - Group Meeting Problems
10/27/2018
1 O OTf

EtO2C N2 O O
TMS PdCl2 COMe
O SnCl2 CsF CuCl, O2 O NBoc
N
Boc CH2Cl2, rt MeCN, reflux DMF/H2O O
rt
72% CO2Et
80%
70%

S. Chandrasekhar et al., Org. Lett., 18, 2044 (2016)

2
O O O
hν
TMS + B O B OTMS
O
MS4A
MeO CF3 hexane, rt
MeO CF3
quant.

H. Kusama et al., J. Am. Chem. Soc., 133, 3716 (2011)

Mes
N
3 N
Cl

Mes
O (0.15 eq.) O
Ph
Et3N (0.2 eq.)
CHO +
Ph
O THF, 66 °C O
O Ph
68%

V. Nair et al., Org. Lett., 16, 6374 (2014)

4 OMe
OMe
MeO
MeO (CH2OH)2
H
p-TsOH (cat.) NCO2Me
CO2Me
O NH toluene, reflux
O H
OMOM 77%
O

K. Ogasawara et al., Org. Lett., 4, 4515 (2002)

 Yokoshima Group - Group Meeting Problems
11/10/2018
1
O Br
SmI2 (2.5 eq.)
BnO t-BuLi NaH thiophenol

Et2O, −78 to 18 °C THF, reflux THF-HMPA, 0 °C

HO
89% 86% 74% BnO

M. G. Banwell et al., New J. Chem., 27, 50 (2003)

2 O CO2Me
O

Bu3SnH
H S AIBN
CO2Me
O N benzene, 80 °C
N
OH 92%
HO

M. T. Crimmins et al, J. Am. Chem. Soc., 120, 1747 (1998)

3
OAc
(C6F5)3PAuCl (10 mol%)
OAc AgSbF6 (10 mol%)
H
CH2Cl2, MS4A, rt
O Ph O H
78% H

H. N. C. Wong and X. S. Peng et al., Angew. Chem. Int. Ed., 57, 11365 (2018)

4
HO Me O HO Me
O2N Ru(bpy)3Cl2·6H2O (5 mol%)
i-Pr2NEt (10 eq.) N
H H
MeCN, 50 °C
H blue LED (λ=465-467.5 nm) H
O O O O
84%
Mechanistic studies suggested the hydroxyamine
was formed as the reaction intermediate.
B-.C. Hong et al., Org. Lett., 17, 2314 (2015)
 Yokoshima Group - Group Meeting Problems
11/17/2018
1
O TFA
CH2Cl2, 0 °C to rt; O
H
CHCl3, 40 °C;
H H
O NaBH(OAc)3
BocN CH2Cl2, rt N
H
72% HO
TBSO H H

M. D. Smith et al., Angew. Chem. Int. Ed., 53, 13826 (2014)

2 CO2Me
(HCHO)n (5 eq.), CO2Me (4 eq.)
toluene, 100 °C;
CO2H N
N
H Bu2SnCl2 (0.1 eq.), 100 °C

78% MeO2C

H. Ardill et al., Tetrahedron, 50, 5067 (1994)

3
HO
O 1) NBS (1.1 eq.) O
1) Ni(COD)2, Mg(OTf)2 O
H
MeOH, 0 °C MeCN, rt
two diastereomers O
OH 2) p-TsOH•H O (dr = 2:1) 2) 3M HCl aq.
O 2
MeCN, rt THF, rt
Br OTBS key structure 59% (2 steps)
95% (2 steps) •THF ring OH
•aldehyde

H. Takikawa et al., Tetrahedron Lett., 59, 4397 (2018

4
O hν A (ketone)
MeO OMe CH2=CH2 1) LiAlH4
+ THF, reflux Me
benzene 90% MeO
Me O B (tertiary alcohol) O
62% 2) BF3•OEt2
(A:B = 4.5:1) benzene, rt Me O H
85%
* Starting material is compound B.

S. K. Sabui and R. V. Venkateswaran, Tetrahedron Lett., 45, 983 (2004)

5
1) TsNClNa, cat. NBS Ts
MeCN, 20 ºC, 61% SnCl4 (2 eq.) N
O
pyrrolidine analogues
O OMe 2) Ph C21H25NO4S CH2Cl2, rt
MgBr MW : 387.15 Ph
Et2O, −30 ºC to rt

A. Armstrong et al., Org. Lett., 7, 1335 (2005)

 Yokoshima Group - Group Meeting Problems
11/24/2018
1
O 1) N2=C(COMe)PO(OMe)2 H O
K2CO3
MeOH, 0 °C to rt, 90%
OPh OPh +
2) (t-Bu)2P(o-biphenyl)AuCl O OPh
AgSbF6, i-PrOH OTBDPS
OTES OTBDPS CH2Cl2 OTBDPS

78% 6%

L. E. Overman et al., J. Am. Chem. Soc., 132, 7876 (2010)

2 Me
O
Cu(OAc)2, O2 Me
O
Me 2,2-bipyridine Me
H DABCO
Me H Me H
DMF, 40 °C
H H
90% O
O

V. V. Rheenen, Tetrahedron Lett., 10, 985 (1969)

H
3 H
CHO
Bn
N
1) LDA N
ClCH2SOPh H H H
H THF, –78 °C;
O KOH (aq), rt BrBa KH, 18-crown-6 A
Bn
N
N 2) LiClO4 THF, –78 °C dioxane, 100 °C H
H dioxane, reflux H
H CHO
87% (2 steps) 90% 85% Bn
N
N
Formula: Formula: H H H
C22H20N2O C27H30N2O
B
A:B = 4:1

J. M. Cook et al., Org. Lett., 3, 345 (2001)

4
Ph
CO
Pd(TFA)2 (5 mol%)
tetrafluoro-1,4-benzoquinone

• MeCN, 80 °C Ph

60%
O
J.-E. Bäckvall et al., J. Am. Chem. Soc., 138, 13846 (2016)
 Yokoshima Group - Group Meeting Problems
12/01/2018
1 1) LAH TBSO
THF, rt
NaH 93% CHO
O O toluene, 110 °C 2) DMP
PMBO CO2Et CH2Cl2, rt O
85% 92% PMBO
TBSO CO2Et

R. K. Boeckman, Jr. et al., Org. Lett., 4, 3891 (2002)

2
Ph A (20 mol%) Ph
AcO Cs2CO3 (1.2 eq.) CN
CN O TsN
+ O
toluene, rt Ph P
BnO2C
Ph BnO2C Ph
74%, 93% ee A

X. Tong et al, J. Am. Chem. Soc., 137, 6400 (2015)

3
Ph C6F5
TMS (2 eq.)
Li
TMS B B
pentane, −65 °C; pentane, rt, 24 h;1
C6F5
PhBCl2 IR: 2118
B(C6F5)3 (1 eq.) filtration; C6F5
1.4 eq.
rt, 10 min phenylacetylene, 60 °C
Ph TMS
66% 87%

G. Erker et al., Angew. Chem. Int. Ed., 57, 14570 (2018)

O
4 N
MOMO

(2 eq.) Li (1.7 eq.) O

Li
O HO
Br Br THF, –78 °C; THF, –78 °C;
N
Br O HCl, EtOH Br
Br O –78 to 0 °C
H (1.3 eq.)
75%
THF, reflux

71% M. A. Tius et al., Org. Lett., 4, 3363 (2002)

 Yokoshima Group - Group Meeting Problems
12/08/2018
1
1) BrMg
THF, reflux Rh(CO)2acac (0.5 mol%)
92% 6-DPPon (10 mol%)
O N PPh2
2) AlCl3, LiAlH4 CO/H2 (1:1, 30 bar) H
O THF toluene, 80 °C 6-DPPon
0 °C to reflux CHO
72% 56%
(E:Z = 1:9)
A. Köpfer and B. Breit et al., Angew. Chem. Int. Ed., 54, 6913 (2015)

2 1) KOt-Bu
DMF, 80 °C
OMIP 70% OMIP
O OMe 2) Ac2O, pyridine, rt
95% O OMe

O O 3) mCPBA OH
O CH2Cl2, 0 °C;
Et3N, 0 °C OAc
75%
MIP = OMe
F. D' Andrea et al, Tetrahedron, 46, 5365 (1990)

3
Me (cat.)
Pd(OAc)2, P(2-furyl)3 Me
I Cs2CO3
+ Br Me
DMF, 90 °C
Me
86%
OH O

X. Luan et al., Org. Lett., 20, 7731 (2018)

4 O
1) mCPBA (3 eq.) ∗
K2CO3 (3 eq.) O
CH2Cl2, rt
70% N
O OH
N
Me 2) Zn
O THF-H2O, rt Me
O
H 62% (dr = 1:19) OH
∗ theoretically 2 equivalents
Y-. J. Li et al., Eur. J. Org. Chem., 1932 (2011)

5
Et [Pd(neoc)(OAc)]2(OTf)2 Et
H TiCl(OiPr)3, EtMgBr 1,4-benzoquinone, CO (1 atm) H
N O O N
O THF, 0 °C to rt 1,2-DCE, rt
O O
H 63% 60% (dr = 2.3 : 1) H

M. Dai et al., Angew. Chem. Int. Ed., 57, 15209 (2018)

 Yokoshima Group - Group Meeting Problems
12/22/2018
1
1) I
HO C6H13 , t-BuLi
Boc N ether, −78 °C
80% H
O * N
HO H O
2) DMP
CH2Cl2/TFA, 0 °C H
C6H13
58% (*dr = 10:1)
3) NaBH(OAc)3
AcOH/THF, rt
75%

G. Pandey and V. Janakiram, Chem. Eur. J., 21, 13120 (2015)

2
TfO

Pd(OAc)2 (1.0 mol%) aq. H2O2 OH

B(pin) Li ligand (1.2 mol%) aq. NaOH
D

Et2O THF, 60 °C THF, 0 °C to rt D H

0 °C to rt
Ph 57% (3 steps)
Ar2P Fe
er = 82:18, dr > 20:1
ligand : Ph NMe2
PAr2
NMe2
Ar = 4-methoxy-3,5-dimethylphenyl J. P. Morken et al., Science, 351, 70 (2016)

3
OBn OBn
BnO OH
BnO OH aq. n-Bu4NOH
hν
TMS
toluene, 100 °C THF DMF, −20 °C BnO
BnO N
N3 80% (2 steps) 77% 49% H

R. Ducray and M. A. Ciufolini, Angew. Chem. Int. Ed., 41, 4688 (2003)

4
Ph Me Ph
Ph
O Ph HO
O
PhCl, 150 °C HO
O Me 63% CHO

S. Zhu et al., Angew. Chem. Int. Ed., 57, 8702 (2018)

 Yokoshima Group - Group Meeting Problems
01/12/2019

1 O
H
AlCl3

O DCM, rt

94% H

K. Kakiuchi et al., J. Am. Chem. Soc., 111, 3707 (1989)

2 O Me3S(O)I
O
NaH H OMe
OMe
DMSO, rt O
O O H
73% O

M. Yamashita et al., Org. Lett., 14, 6048 (2012)

3
E
E +IPh-OTf Ph
KHMDS H E E
+ E
Ph THF, rt E
E Ph
E
E E E
E
E = CO2Et 40% 16%

H. Y. Lee et al., Org. Lett., 12, 2672 (2010)

4
NH
NH ·2HCl
O OBn OBn (10 mol%) NaBH4 OBn OBn
+
H Ph DCE, 90 °C MeOH, rt OH
Ph
80% (2 steps)

T. H. Lambert et al., J. Am. Chem. Soc., 134, 18581 (2012)

 Yokoshima Group - Group Meeting Problems
02/09/2019

1 Me Me
1) (COCl)2 NC CO2Et
CbzHN CO2H
O CH2Cl2 N Me Me H
reflux HO H2N CO2Me A, i-Pr2NEt
Me N CO2Me
N N A •HCl CbzHN
Me O 2) KPF6 MeCN, rt Me Me DMF, rt O
CH2Cl2/H2O Me Me
rt 89% 99%
84% (2 steps)
A. El-Faham, F. Aibericio et al., Chem. Eur. J., 15, 9404 (2009)

2 OH
H TBAI, Tf2NH
HO I
MS5A, CHCl3, −20 ˚C; O
O O +
HFIP, rt O
O Me
63% (dr > 19:1) Me
H

G. Alachouzos and A. J. Frontier, J. Am. Chem. Soc., 141, 118 (2019)

G. Alachouzos and A. J. Frontier, Angew. Chem. Int. Ed., 56, 15030 (2017)

3
Si Tf2O (1.1 eq.), DTBMP (1.1 eq.)
O O CH2Cl2, rt;
CHO DIPEA (5.0 eq.), reflux; N
N MeO2C H
H OH
TBAF (1.1 eq.), rt
NC CHO
69%
CO2Me
P. Boissarie and G. Bélanger, Org. Lett., 19, 3739 (2017)

4
NTs
[Pd2(dba)3]•CHCl3 1) mCPBA
(2.5 mol%) CH2Cl2
O Ph (S,S)-Chiraphos 0 °C to rt TsN
(5.0 mol%) 70% O
+ (S)-nine-membered ring Ph
O toluene, 0 °C 2) BF3•Et2O O
O Ar
THF, rt
O O 90%, 87% ee 82%
Ar = Cl
Ar

Y. Lan and Y. Zhao et al., J. Am. Chem. Soc. 139, 15304 (2017)
 Yokoshima Group - Group Meeting Problems
02/23/2019
1 Me

TMS
N N Cl t-BuOK N
H Me + NO2
TMS EtOH, reflux; THF, 80 °C
N NaOH aq.
H 84%
67% N H CHO
NO2 H
(2 eq.) (1 eq.)
D. B. C. Martin and D. Vanderwal, J. Am. Chem. Soc., 131, 3472 (2009)

2 Me i-Pr LDA i-Pr

THF, –80 °C; Me
Ph N N
ZnBr2
–80 °C to rt Ph
NC
71%

F. Chemla et al., Chem. Eur. J., 16, 12668 (2010)

3 CO2H
Ac2O S N O S
S N O + N O
reflux O
O Ph
O Ph O Ph
1 2
17% 29%
2 formed from 1

T. M. V. D. Pinhoe. Melo et al., J. Org. Chem., 67, 4045 (2002)

4 OMe
Me
Li
Me
O Me H
i-PrO O THF, –78 °C;

i-PrO Me
i-PrO O OH Me
Li Me , –78 °C to rt i-PrO

44%

L. A. Paquette and F. Geng, J. Am. Chem. Soc., 124, 9199 (2002)

5
Me Me
1) Rh(acac)(CO)2, CO OH O OH
benzene, 60 ºC
Si i-Pr
O H Me 2) H2O2, KF Me Me
THF-MeOH, 23 ºC dr = 6:1
iPr 71% (2 steps)

J. L. Leighton et al., Org. Lett., 10, 5593 (2008)

 Yokoshima Group - Group Meeting Problems
03/02/2019

1
1) CH3CHI2, Et2Zn 3) PhI(OCOCF3)2
OTMS CH2Cl2, rt TfOH (cat.)
MeO2C
2) TBAF MeOH, rt N
TsN Ts
THF, rt
90%, dr = 9:1 (2 steps) 69%

M. Kirihara et al., Tetrahedron, 54, 13943 (1998)

M. Kirihara et al., Tetrahedron, 55, 2911 (1999)

2
O Tricyclic O H
hν, MeOH aq., rt; MeLi
O Compound
O
55 °C Et2O, –78 °C; Me
C14H16O3
Me OAc reflux HO H
60%
63%

F. G. West et al., Org. Lett., 10, 3733 (2008)

3
Pd2(dba)3•CHCl3 (2.5 mol%)
O O chiral ligand A (15 mol%)
O O CO2Me
Ph +
O O
O CO2Me CHCl3, 25 °C
Ph O
95% (99% ee)

O
P N
O
A

H. Guo et al., ACS Catal., 9, 1645 (2019)

4
O
(10 mol%)
PMP PMP
OH (COCl)2 (1 eq.) Cl
CO2Me CO2Me
Ph PhCF3, 80 °C Ph

90%

C. M. Vanos and T. H. Lambert, Angew. Chem. Int. Ed., 50, 12222 (2011)
 Yokoshima Group - Group Meeting Problems
03/09/2019

1
O R
H R CF3
R Yb(OTf)3 (5 mol%)
CF3 CF3
O Ph + O
toluene, reflux N H N
Bn Bn Bn
N Ph Ph
R=H 90% 0%
R = Bn 0% 86%

T. Akiyama et al., J. Am. Chem. Soc., 136, 3744 (2014)

2
NEtBoc
NEt
H
O H Au(IPr)Cl, AgSbF6 TFA O
O CH2Cl2, rt 59% (2 steps)
N
N H
O

H. Zheng et al., Org. Lett., 20, 4439 (2018)

O2N O CH(NMe2)3 HN O

THF, reflux
N 80% N
H Me H Me

J. Bonjoch et al., Tetrahedron, 50, 9769 (1994)

 Keys to the Problems (03/09/2019)

I
.

A- H .

Hb ]
OR
-

÷
d-
of'fbJ

HIT
④
CF 3

IN
Hb ] -

A
o
i.

f
.

H It - as
'
-

I
Bn Cfs I

= Ph
If
→

in in
LEH f. f.
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shift

l⇐÷÷÷
H
✓

CHI
.

.
¥
.
... BC " ,
,
. - o -
Ub )
HE

Bn 1.
→

5. CHI -
shift
IE
E':
H

*
in
→
-
Bn

Yokoshima Group - Group Meeting Problems

 Keys to the Problems (03/09/2019)

I Bn
R
-

-
. .

d-
-
Hd
o

an

EI÷Em
- a '

÷ Yo
Haha
=
it
an
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⑦
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✓
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o

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Cfs

- - Ph
Bn

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→
Ma
Esi \
o

be
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Yokoshima Group - Group Meeting Problems

 Keys to the Problems (03/09/2019)

1-
Sb Fb
.

Ag
CAT
"
%II
An C Ik ) Cl

Aga

EEE
"

→
→
. .
. .

T.io
① - H
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→
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it it .
a

Step I

÷÷
Et
"
I H

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Yokoshima Group - Group Meeting Problems

 Keys to the Problems (03/09/2019)

3 .

- -

oink
-

?
'

Fin T

Tna
"

"
→ " ' o_O

Lorne
05 .

finish
Whee Amer

→ → .
luther me
Keat mean ,

Ill
⑦ lumen

i
father
-
-
H
Mesh It
'
T ? Me Her

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.

H Ho
H
F
k¥11
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i.
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→
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Yokoshima Group - Group Meeting Problems

Yokoshima Group - Group Meeting Problems 04/06/2019

1
cat. H3PO4 air H2SO4 OH

benzene 80-130 ºC 93%

200-250 ºC
25%
20%

F. Mizukami et al., Science, 295, 105 (2002)

2
Ph2BOH (10 mol%) OMe
OMe Ir[dF(CF3)ppy]2(dtbpy)PF6 (1 mol%)
O quinuclidine (20 mol%) Me O
Me O + HO
HO HO
OMe MeCN, 23 °C, Blue LED O
HO
OH
70% (dr = >20:1) O
(2 eq.) (1 eq.)

M. S. Taylor et al., J. Am. Chem. Soc., ASAP

3
O KOH, KI O
TMS [(C4H9)4N]2SO4 EtAlCl2 H
+ SO2Ph A
OMs DCM-H2O DCM, reflux

86%

C8H18O3SSi C15H20O3S C22H34O3SSi

single diastereomer

B. M. Trost et al., J. Am. Chem. Soc., 105, 4849 (1983)

4
O2, hν
tetraphenylporphyrin
Ph DCM, 0 °C; N
N N CO2H
N3 Me2S
O Ph
90%

R. Altundas et al., Org. Lett., 15, 4790 (2013)

 Yokoshima Group - Group Meeting Problems 04/13/2019
1
O
HO PhI(OAc)2, MeOH Pd(OAc)2 O O
2,6-lutidine Ph3P, Et3N OMe OMe
MeO MeO
I
O CF3CH2OH, –40 °C; PhCF3, 150 °C O O O O
OMe toluene, 60 °C
CF3 CF3
CF3
64% major, 56% minor, 11%

J. T. Njardarson et al., Angew. Chem. Int. Ed., 52, 8648 (2013)

2
O H
hν NiCl2·6H2O HO N
H2N Pyrex NaBH4

S MeCN, 0 °C MeOH, THF

0 °C to rt
O quant. Me
56%

J. D. Winkler et al., J. Am. Chem. Soc., 128, 9040 (2006)

3
PhLi (3 eq)
THF, –78 °C; CyBpin; BocN
Br
Br NH2·HBr Bpin
s-BuLi (1 eq) AcOH Cy
TMEDA; –78 °C to rt;
Boc2O

68%

V. K. Aggarwal et al., J. Am. Chem. Soc., 141, 4573 (2019)

4
1) NaH, CS2
O O THF, 0 °C;
MeI, 0 °C Ph
O
Me N Et2Zn, CH2I2 74%
N
Me
O CH2Cl2, 0 °C; 2) n-Bu3SnH, AIBN
O OMe
benzaldehyde, 0 °C toluene, reflux O
OMe 73%
70%

C. K. Zercher et al., J. Org. Chem., 71, 8140 (2006)

5
1) NaIO4
O O
n-Bu3P O MeOH-H2O, rt
SEt , rt O
toluene, rt; Cl 95% N
N3 N SEt SEt
O
O
CO2Et 2) TFAA, TFA
O 44% CO2Et
CO2Et CH2Cl2, 0 °C to rt
76%

microwave
150 °C;

A. Padwa et al., J. Org. Chem., 72, 538 (2007)

Yokoshima Group - Group Meeting Problems 04/20/2019

1
O
O 1) CpMgCl
THF, 0 °C to rt
O
O
2) hydroquinone
I benzene, reflux
O O
Cp : Cyclopentadienyl major, 68% minor, 6%

J. R. Stille and R. H. Grubbs, J. Org. Chem., 54, 434 (1989)

2
OH H OH
mCPBA AlEt3
O
CH2Cl2, rt THF, rt
CO2Me
87% 57% O

P. Xie et al., Org. Lett., 18, 1944 (2016)

3
Ph
Et
diketene Ph
TMSOTf
N O
Et benzene, reflux
O
63% O CH3
NH

A. Padwa et al., J. Org. Chem., 60, 2952 (1995)

4
OH O
1) NaBH3CN
OH BF3•OEt2
THF, 23 to 66 °C TfOH
C22H31NO2
H H H 2) CrO3, H2SO4 MeNO2, 23 °C H H H
N H2O-acetone N
H H
H 0 °C 70% H
O 68% (2 steps)

R. Sarpong et al., ChemRxiv (2019)

5 Me O
LiTMP (2 eq) N2
CH2Br2 (2 eq)
THF, −78 °C; Me
n-BuLi (5 eq) Me Me
OTIPS
Me −78 to 25 °C; hν (Pyrex)
OTBS Me
MeO2C TIPSCl benzene, rt
−78 to 0 °C Me Me OH
64% OTBS
52%
R. L. Danheiser et al., J. Org. Chem., 59, 4844 (1994)
 Keys to the Problems (04/20/2019)

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Yokoshima Group - Group Meeting Problems

 Keys to the Problems (04/20/2019)

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Yokoshima Group - Group Meeting Problems

 Keys to the Problems (04/20/2019)

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Yokoshima Group - Group Meeting Problems

 Keys to the Problems (04/20/2019)

4 .

iii.
OH
I
"
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Yokoshima Group - Group Meeting Problems

 Keys to the Problems (04/20/2019)

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Yokoshima Group - Group Meeting Problems

 Keys to the Problems (04/20/2019)
Lit

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.

f
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-
-
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→
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-

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OH
: LOTBS

Yokoshima Group - Group Meeting Problems

Yokoshima Group - Group Meeting Problems 05/11/2019

1
OTBS Ph
OTBS Py•TfOH (0.2 eq.) Me N
Me OH + Ph
Ph MeCN, rt;
TsOH (0.3 eq.), rt;
PhNH2 (4.0 eq.), reflux

80%

R. Kartika et al., Org. Lett., ASAP

DOI: 10.1021/acs.orglett.9b01032

2
AgSbF6 (10 mol%) Me
Ph Ph +
CHCl3, 40 °C
Ph
Ph
83%

C. Chen et al., ACS Catal., 8, 7760 (2018)

3
MeO2C
MeO2C Br Bu3SnH
CO2Me AIBN CO2Me

CO (85 atm)

42% O

I. Ryu et al., J. Chem. Soc., Perkin Trans. 1, 1591 (1998)

4
OH
CO2i-Pr LDA decane CO2i-Pr
Me
n-Pr O THF 180 °C
−78 °C to rt
74% Me
87%

M. Hiersemann et al., Eur. J. Org. Chem., 483 (2001)

Yokoshima Group - Group Meeting Problems 05/18/2019
1
NC
N3
N3 CH(OMe)2 H O
O O N
O
(TMS)2NH
O NH
HFIP, rt CH(OMe)2
O HO
Cl3C
85% (dr = 1.7:1)

J. Isaacson and Y. Kobayashi, Angew. Chem. Int. Ed., 48, 1845 (2009)

2
Li (excess)
THF, –30 °C;
filtration;
BPh
N PhBpin N
Ph Ph
–30 to 25 °C

82%

H. Yorimitsu et al., Org. Lett., ASAP

DOI: 10.1021/acs.orglett.9b01353
3
O OH
HO
Me O
Cl PDC NaOAc DIBAL
Me
Me Cl
Me H DMF, rt Ac2O, 140 °C toluene Me Me
Me Me
–78 °C to rt
68% (2 steps) Me
Me
85%

E. M. Carreira et al., Angew. Chem. Int. Ed., 58, 2490 (2019)

4
Ph toluene, 100 °C; Ph
PPh3 (10 mol%), 60 °C; MeO2C
N N
Cy
O2 (1 atm), 0 °C Cy
MeO2C OH
80%

M. Yoshida et al., Angew. Chem. Int. Ed., 53, 14550 (2014)

5
LDA (2.6 eq)
O O THF, 0 °C; PBu3 H
N
O OEt
OEt THF, 45 °C
O
N3 O
64%
–78 °C to rt

57%

P. Langer et al., Chem. Commun., 3044 (2003)

 Yokoshima Group - Group Meeting Problems 05/25/2019
1
LDA
THF, −78 to 0 °C; O
O TMSCl
0 °C to rt;
O NEt2
MeI (Scavenger of base) OH
rt;
benzaldehyde
rt to 35 °C

62%

R.-J. Chein et al., Org. Lett., 20, 5362 (2018)

2
NHC cat. O
O (10 mol%) Ph N

Cl O Et3N Mes N N
+
Ph H DCE, 0 °C to rt O O BF4
Cl
78% NHC cat.
(>20:1 dr, 90% ee)

M. A. Pericàs et al., Org. Lett., 21, 3187 (2019)

3
TMS
n-C4H9
O Tf2O TfOH
2,6-lutidine MeCN, 60 °C; S
S
Me alkyne n-C5H11
MeCN, 80 °C NaI, 60 °C

89% 71%

A. J. Eberhart and D. J. Procter, Angew. Chem. Int. Ed., 52, 4008 (2013)

4
A
Ag2CO3 O Ru(bpy)3Cl2•H2O O
TMSN3, H2O 2,6-lutidine
A Br
OH CN
DMSO, 80 ºC C15H13N3O MeCN
Ph Ph
blue LEDs, rt
52%
92%

J. R. Donald and S. L. Berrell, Chem. Sci., ASAP

DOI: 10.1039/c9sc01370a
5
MeO2C OTBS
BocN
H CO2Me LHMDS (2.3 eq.) Me
N THF, –40 °C; HN
H
MeO Me OTBS I2 CO2Me
–40 °C to rt CO2Me
NHBoc 67% OMe
D. Ma et al., J. Am. Chem. Soc., 134, 9126 (2012)
Yokoshima Group - Group Meeting Problems 06/01/2019

1
O
Ph
Rh2(S-DOSP)4 (1 mol%) Ph
N
+ Me
Me Me N
O N 1,2-DCE, 70 °C Me
Ts N
84% Ts
3 eq. 1 eq.

M. L. Davies et al., J. Am. Chem. Soc., 135, 4716 (2013)

2
tBu SbF −
6
tBu P Au+-NCMe

(5 mol%) Ph
+
Ph DCE, 120 °C

76%

A. M. Echavarren et al., Angew. Chem. Int. Ed., 53, 14022 (2014)

3
O
CHO
Cl S N C O
i-Pr O
O
DCM, rt OH
6d
then NaOH aq. i-Pr

20%

D. P. Veloso et al., J. Chem. Soc., Perkin Trans. 1, 585 (1993)

4
1) p-MeC6H4SSCl
DCM, 0 °C hν
tricyclic compound
C7H8S S
2) Na2S MeCN

T. Fujisawa and T. Kobori, J. Chem. Soc., Chem. Commun., 1298 (1972)

Yokoshima Group - Group Meeting Problems 06/08/2019

1
1) Rh2(esp)2 (cat.) Me Me
CH2Cl2, rt O
EtO2C CHO 60% H
EtO2C O
+ O
N2 2) Sc(OTf)3 (cat.) O
O H
CH2Cl2, 40 °C Me Me
98%
esp

M. L. Piotrowski and M. A. Kerr, Org. Lett., 20, 7624 (2018)

2 Me Me
1) NH2NH2•H2O
O MeOH, reflux bicyclic PhB(OH)2 Ph
N compound N
2) PhI(OAc)2 1,4-dioxane
CH2Cl2, rt 100 °C
Br 85% (2 steps) Br
84%

R. Shen et al., Org. Lett., 21, 4148 (2019)

3
O Me
Me OMOM
SmI2, H2O LHMDS Mn(dpm)3 (cat.)
Me
OMOM THF, 0 °C; TIPSOTf PhSiH3, TBHP

TMSCl THF i-PrOH, rt

−78 to 0 °C Me
Me TIPSO Me O
O 93% (dr = 23:1) 55%
Me 76%

S. E. Reisman et al., J. Am. Chem. Soc., 140, 1267 (2018)

4 O
O R
R O (10 mol%) 1) O3
O acetone, rt
O O O
SiEt3 77%
S OEt Ph OEt
Ph
EtOAc, reflux 2) Cs2CO3
S SiEt3
18-crown-6
92%
1,4-dibromobutane
(R=C11H23)
MeCN, reflux, 65%
(dr = 2.1:1)

S.-G. Li and S. Z. Zard, Org. Lett., 16, 6180 (2014)

5
H
n-Bu3SnH, AIBN O

toluene, 110 °C
S Ph H
O 46%

P. Renaud et al., Angew. Chem. Int. Ed., 41, 4323 (2002)

Yokoshima Group - Group Meeting Problems 06/22/2019
1
Me
Cl
Me 1) K2CO3
HFIP, rt O Me Me
Br
Me Me
2) TFA O
CO2tBu CH2Cl2, rt Br

CO2tBu 75% (2 steps)

HFIP = hexafluoroisopropanol
N. Z. Burns et al., J. Am. Chem. Soc., 139, 13562 (2017)

2
BuMgBr ZnBr2 SiMe3
Et2O, rt; THF, rt; Me
Me3Si H
1 M HCl aq., −5 °C
OSiMe3
O
89%
SiMe3
reflux;

I. Marek et al., Org. Lett., 7, 5313 (2005)

3
O
O
• t-butyl nitrite

EtOH, rt
N
Ph Ph
82% O
EtO

Y. He, T. Feng and X. Fan et al., Org. Lett., 21, 3918 (2019)
4
Mn(acac)3 (10 mol%) OH
OH
N
MeOH, rt
N3 87% H

Y.-F. Wang and S. Chiba, J. Am. Chem. Soc., 131, 12570 (2009)

5
3) PhNCO, Et3N
1) MeNO2, Et3N 1,5-hexadiene (excess)
O THF-EtOH, rt benzene, reflux O
85% 74% O
H NC I + H
2) TMSCl, Et3N
4) iodine monochloride
THF, rt
84% CH2Cl2, -78 ºC
53%

X. Beebe, N. E. Schore and M. J. Kurth et al., J. Org. Chem., 60, 4196 (1995)
Yokoshima Group - Group Meeting Problems 07/06/2019

1
O O
H
Ph HN Ph Yb(OTf)3 (10 mol%) Ph
+
O toluene, 80 °C H
OH O
N H
87% Ph H

S. Baskaran et al., Org. Lett., 21, 3822 (2019)

2
CN
(10 eq.) CN
Bu3SnH
AIBN Si Si
O O
Si TMS benzene
reflux
TMS Br
54%
α-CN : β-CN = 4 : 1

M. Malacria et al., J. Org. Chem., 63, 6764 (1998)

3
N O
[Pd2(dba)3] (2.5 mol%)
Ph N Me
P(4-CF3C6H4)3 (10 mol%)
O Ph
Me
1,4-dioxane, 80 °C
Me Me
87%

K. Ohe et al., Angew. Chem. Int. Ed., 50, 11470 (2011)

 Yokoshima Group - Group Meeting Problems 07/13/2019

1
NH2 CHO 1) MeCN, rt;
TFAA, 0 ºC; N
OHC NaBH3CN, rt, 66% O
+ O
CO2i-Pr 2) NaOH, EtOH, 75 ºC
MeO N 88% N H
MeO
OMe Me TMS 3) K3Fe(CN)6, NaHCO3
t-BuOH-H2O, rt, 92% OMe Me

E. J. Corey et al., J. Am. Chem. Soc., 121, 6771 (1999)

2
OTBS Pd2(dba)3 (5 mol%) OTBS
Me tris(2-furyl)phosphine (25 mol%) Me O
A (50 mol%), Cs2CO3
I + NTol
THF, 90 °C O
N (Schlenk tube) N
Me OBz Me A
85%

Q. Zhou et al., Chem. Commun., 55, 8816 (2019)

3 O
S OEt
Me
S Cl
Cl O
SO2Me DLP (35 mol%) K2CO3
CO2Et H3C(H2C)10 O
CO2Et 2
DCE, reflux EtOH, 50 °C
Me DLP
63%
55%
S. Z. Zard et al., Org. Lett., 11, 2832 (2009)

4
O Boc
Br
Ph O N
CO2Me KOt-Bu K2CO3 MeNH2
+ CO2Me
MeN
NHBoc THF, rt CO2Me
acetone, 40 °C THF, 100 °C
Ph
90% 73% 61%

M. Penning and J. Christoffers., Eur. J. Org. Chem., 1809 (2012)

5
TsHN n-BuLi (3.5 eq.) (CH3)2CHCO2H
HO2C
N MeI DCC
Me Me Me Me
THF, −50 °C; DMAP (cat.) LDA, TMSCl
Me
Me n-BuLi (8 eq.) CH2Cl2, rt THF, −78 to 75 °C Me
O O
H H OTBS −50 °C to rt; H H OTBS
Me (HCHO)n 73% 80% (dr = 6:1) Me

64%
R. J. Sharpe and J. S. Johnson, J. Am. Chem. Soc., 137, 4968 (2015)
Yokoshima Group - Group Meeting Problems 07/27/2019

1
PhI (2.5 eq)
Pd(OAc)2 (12 mol%)
Me glycine (32 mol%)
CHO CF3CO2Ag (1.6 eq)
Me
HFIP, 105 °C
(sealed tube)

91%

L. Zhou et al., Org. Lett., 21, 80 (2019)

2
Acetophenone
I t-BuOK
hν
CH2COPh
I DMSO, 30 °C;
NH4NO3 aq.

83%

R. A. Rossi et al., J. Org. Chem., 62, 4260 (1997)

• [Rh(CO)2Cl]2 (5 mol%) H
Ph Ph +
TsN 1,4-dioxane, 80 °C TsN Ph

70% TsN H
1 : 7

C.-H. Liu and Z.-X. Yu, Angew. Chem. Int. Ed., 56, 8667 (2017)

4
O O TMS
TMS
chlorobenzene
OTBS 150 °C
(sealed tube) OTBS

82%

T. R. Hoye et al., Org. Lett., 21, 1672 (2019)

Yokoshima Group - Group Meeting Problems 08/03/2019

1
Me OH Me
Ti(Oi-Pr)4 Cy
O O c-C5H9MgCl

Cy THF, 0 °C
H H H OH H
78%

G. C. Micalizio et al., Org. Lett., 21, 6126 (2019)

2
MeO2C H H CO2Me 1) PCC MeO2C
H H
BHT DCM, rt
H
benzene 2) BF3•Et2O
240 °C H
DCM, 0 °C
TBSO (sealed tube) RO O
60%
64% (2 steps)
R=H
R = TBS

M. L. Snapper et al., J. Am. Chem. Soc., 123, 5152 (2001)

M. L. Snapper et al., Org. Lett., 7, 5785 (2005)

3
O
Et [Ni(cod)2] (5 mol%) H Et
Ph P(4-MeC6H4)3 (15 mol%) O
+ Et
toluene, 100 °C Ph
Et H Ph
Ph 64%

H. Horie, T. Kurahashi and S. Matsubara, Angew. Chem. Int. Ed., 50, 8956 (2011)
 Yokoshima Group - Group Meeting Problems 09/07/2019
1
Me H
2-bromopropene
O Me
t-BuLi air O

O Et2O, −78 °C toluene, reflux CDCl3, 5 °C

OH
70% 40% 99% Me
Me CHO

A. L. Zografos et al., Org. Lett., 15, 152 (2013)

2
CO2Et
n-Bu3SnH n-Bu3SnH CO2Et
THF, rt; cat. Et3B H
CN
CN N
N I2, 0 °C THF, rt, air Et
Et
O
O 64% 81%

C. M. Beaudry et al., Angew. Chem. Int. Ed., 58, 12595 (2019)

3
Ph Ph
O O TBAI, TBHP
O
+ S O
N CH3CN, 60 °C O N
O HN S
S Me NH2 4 Å MS Me
Ph O Ph O

60%

S.-J. Tu et al., Org. Lett., 17, 6078 (2015)

4
Au(PPh3)Cl Et3N
PivO H AgOTf, A CHCl3-MeOH Me H
Me
Me Me CH2Cl2-MeCN, 24 °C 24 °C; Me
CH2Cl
TIPSO OMe N
TIPSO catecholborane
NH2NHTs, 40 °C Me Me N
Me 0 °C; H H 2BF4-
H F
CsOAc, 65 °C
81% (dr = >20:1) A
selectfluor®
58% (dr = >20:1)

D. Sarlah et al., J. Am. Chem. Soc., 141, 14131 (2019)

5
OH
NH
N3 PyHBr3 (3 eq.) N3
CbzHN N
H K2CO3 (10 eq.) HN
O
CH2Cl2/H2O (1:1), rt CbzN N Br
Br
MsO

*Yield of this step wasn't written in original report.

Y. Sawayama and T. Nishikawa, Angew. Chem. Int. Ed., 50, 7176 (2011)
Yokoshima Group - Group Meeting Problems 09/28/2019

1
Ph Ph
PhCHO (2.5 eq) Ph O Ph
MeO Me BF3•Et2O (3.5 eq) MeO O
MeO
DCM, rt Me Me
Me
OMe 96% MeO Me OMe Me

G. Sudhakar et al., J. Org. Chem., 84, 7815 (2019)

2
O
O O O H
OMe TBAF PhI(OAc)2 SmI2 O H O O
H C22H30O7
OTIPS THF, 0 ºC MeOH, 65 ºC THF-MeOH
0 ºC to rt H H OH
OH 70% (2 steps)
90%
C30H48O6Si C20H26O5

H. Ding et al., Angew. Chem. Int. Ed., 58, 8556 (2019)

3
1) Na2S2O8 (2.0 eq)
TBS I O AcOH-H2O, 50 °C
Ph OH 78% Ph O TBS
+ O
2) tBuOK
THF, 0 °C;
HCl aq.
78%
X.-H. Duan et al., Org. Lett., 17, 4798 (2015)

4
1) PtCl2 (2 mol%)
OPiv DCE, 70 °C O
+
2) K2CO3
MeOH, rt O

(69% ee) 28% 42%

(12% ee) (60% ee)

C. Fehr and J. Galindo, Angew. Chem. Int. Ed., 45, 2901 (2006)

5
[Rh(CO)2Cl]2 Ts
Ts
N dppe N

Ph toluene Ph
110 °C

77%

M. A. A. Walczak and P. Wipf, J. Am. Chem. Soc., 130, 6924 (2008)

 Yokoshima Group - Group Meeting Problems 10/05/2019

1
R R
Me O
R E E Me3Al, EtSH O O

R R CH2Cl2-heptane
reflux R
O
R= 75%

E = CO2Me H. Xu et al., Org. Lett., 21, 8075 (2019)

2
O
H LiClO4 CO2H O
O Cl O
Et3N OH time time Ph
O + OH
Ph A B O
MeCN-H2O Ph
O Ph Ph
H rt HO
O
Both A and B
are di-ketone 25%
C13H13ClO2 C26H26O5 C26H26O5 C26H28O6

A. Hassner et al., J. Org. Chem., 58, 5699 (1993)

3
t-Bu t-Bu
Si
Me
Me
AgOTs (10 mol%)
O HO CO2H
toluene, −25 °C;
O n-Bu Me
Me Me
HF•pyridine, rt
O Me n-Bu
77%, 97% ee

K. A. Woerpel et al., Org. Lett., 9, 4651 (2007)

Yokoshima Group - Group Meeting Problems 10/19/2019
1
5 mol%
Me
Li Grubbs 1st H O
O generation cat.
Et3N Me

Br Br
TFE/Et2O THF ethylene
–78 °C to rt –78 to –30 °C CH2Cl2, rt H

70% 90% 50%

M. Harmata and S. Wacharasindhu, Org. Lett., 7, 2563 (2005)

2
1) 4-HOC6H4B(OH)2
N N
MS3A, hν O
THF, rt
N
N
Cl OMe 2) HCl
EtOH, rt* Cl OH

* probably under water-coexisting conditions

C. Jamieson et al., Chem. Sci., Recent Article

DOI: 10.1039/C9SC03032H

3
O O

NH N
N Cs2CO3 N
+ S CO2Me
Br
Br MeCN, 35 °C CO2Me
Cl Cl
72%

Z. Wang et al., Org. Lett., 21, 7361 (2019)

4
O
O O N cat. ZnCl2 Me
+ O Ts
ClCH2CH2Cl, 60 °C NTs
Me Me Me
H O
70%

L. A. López et al., Angew. Chem. Int. Ed., 51, 8063 (2012)

5
O
1) hν, acetone, rt 3) RuO2, NaIO4 O H
75% CCl4/H2O/MeCN, rt; H
O C13H17NO2
H
2) DPPA, Et3N 2 M H2SO4 aq.
HO2C 1,4-dioxane, reflux 55% (dr = 2:1)
89% H
O
C13H18O3 C12H16O3

K. I. Booker-Milburn and J. K. Cowell, Tetrahedron Lett., 37, 2177 (1996)

 Ke eP be (10/19/2019)

'

" -
a a
→ to →

.
-1
1st step

i
" '

i
→ → =
.
⇐

, I
-

2nd step

→ → . . =
a
a
.

HIT
ers
I I
o
→

HIT o
^ -

Y aG -G Mee P be
 Ke eP be (10/19/2019)

2 .

one

¥
" "

III I
-

one
:*
← . .

pine
- -
pine pine

EI EI
Elliott
.

BAH
NH
'D

£13
-
IH HQ -0 OH
,
-
→
→ OH → N -
-

, on
''

. o .
. .

1st Step

¥5
me
pine

o.ee#
One
1-

Hee

H ⑦
EI
'D
EI °
H I 'D
-
IH H "
-

I
thy
→

Eto
→ '

.
. o . .
a
:
OH , I

Y aG -G Mee P be
 Ke eP be (10/19/2019)

3 .

No
Itsy
Geos

go
I
's
It tone
"
-
one
one →
or
→
#
H
T :B

I OF

IT
ox

teen
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al -04kt I

one
- -

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→
→ one one one

. .
-

Y aG -G Mee P be
 Ke eP be (10/19/2019)

4 .

En )

i
→
en
i
→
→
a

"
i →
- ⇐
→
I
→

I
" yes "
→ -

y a
ED
→ -

I -

Ei .

Y aG -G Mee P be
 Ke eP be (10/19/2019)

5 .

no
:* IF
:#
¥¥µ
:*
*
Dl " A
'
±

HE
' →

pH 1¥
⇒

k¥7111
"
,
E
↳ Ets
Pho -
=

phot Ey join

'
Ruo . Knox

Y :
oi÷
"

,
"

one

't:*
Y a
EH to I
" "

*
→ →
*
To N N N
' ' '
d d d
"
o I g
Ces High 02

±
pH⑦

to

÷÷i÷¥÷÷÷"÷÷÷÷÷ .

±
"
o

. . .

mihorma.jo
Hts
Ay,
- .

,
OH O
He OH . H,

Y aG -G Mee P be
 Yokoshima Group - Group Meeting Problems 11/09/2019
1 A (major isomer)
28%
O Me O MsOH Me
+ 1) HBr, AcOH
Boc2N OTBDPS MeOH, 40 °C H
4 4 MeOH, rt O
B (minor isomer)
11% 2) NaOH, H2O HH
MeOH, rt N
80% (2 steps)
(−)-Lycopodine

H. Takayama et al., Tetrahedron Lett., 60, 187 (2019)

2 Cu(OAc)2 (20 mol%)

NH2 TBHP NH2
OMe NaOH
HS O
N +
N O CH3CN, 80 °C, air
H S OMe
72%

Q. Song et al., Org. Lett., 21, 8869 (2019)

3
O HN
OH O
Ph
Ph Ph Ph
cyclopentenone Me H
O Me THF, rt toluene, 160 °C
sealed tube N
90%
85%, dr = 5:1

Y.-W. Huang and A. J. Frontier, Org. Lett., 18, 4896 (2016)

4
tBu
Si
tBu
tBu tBu
cat. AgOCOCF3 Oxone, NaHCO3
Si Ph
OTIPS O
benzene, rt; acetone/H2O, rt HO OTIPS
PhCHO, rt OH
70%
72%

K. A. Woerpel et al., Angew. Chem. Int. Ed., 54, 4295 (2015)

Yokoshima Group - Group Meeting Problems 11/16/2019

1
OMe CO Me
MeO O toluene CO2Me O 2
reflux
N
O A
N 74%
OH O

C9H14N2O3 C6H8O2 C15H22O5

K. Kassam and J. Warkentin, J. Org. Chem., 59, 5071 (1994)

2 O
O Rhodium(II) octanoate
N2 (cat.) O
MeO2C CO2Me
MeO2C
DCM, rt MeO2C
N
H
70% N
O dr = 1:1

A. Padwa et al., J. Org. Chem., 60, 53 (1995)

3
O OH
MeO Me
O TsOH O
acetone, reflux
HO
n-Bu n-Bu
82%

D. Kim et al., Chem. Commun., 2263 (1997)

4
TMSOTf (2 eq.) I
I(OAc)2 Et
CH2Cl2, −78 °C; Et
Et Et N
N
Bu3Sn
, −78 °C; H
S
S , −78 °C

78% (d.r. 90:10)

B. Peng et al., Angew. Chem. Int. Ed., 58, 17210 (2019)

Yokoshima Group - Group Meeting Problems 12/07/2019
1
1) DMP O O
cat. Pd(PPh3)4, i-Pr2NH CH2Cl2, rt O
O OH
microwave 77% O
O O
Br benzene 2) cat. RuCl3, NaIO4
MeO2C 160 °C CCl4-CH3CN-H2O
50% H CO2Me
60%

J. Suffert et al., Angew. Chem. Int. Ed., 50, 3285 (2011)

2
H
O Ca(NTf2)2 (5 mol%) N
NH2 NHNs n-Bu4NPF6 (5 mol%)
+ NNs
HO toluene, HFIP, 20 °C; I
I O
Et3N

87%

V. Gandon and D. Lebœuf et al., Angew. Chem. Int. Ed., Early View
DOI: 10.1002/anie.201911761

3
O

NO2 EtO2C CO2Et

MgCl
CO2Et
THF, −70 °C toluene, 80 °C CO2Et
Br
65% 74% N
(E:Z = 98:2) Br

G. Bartoli et al., J. Org. Chem., 55, 4456 (1990)

J. Yang et al., Angew. Chem. Int. Ed., 51, 5110 (2012)

4
Me 1) t-BuOK, DMSO 3) m-CPBA, NaHCO3
Br O
30 to 40 °C, 60% CH2Cl2, 0 °C
Br
OH 2) HBr aq, THF 4) ZnBr2, benzene
Me
Ph 0 °C reflux, 80% Me
Ph

W.-D. Z. Li and Y.-R. Yang, Org. Lett., 7, 3107 (2005)

5
Me
H O
(CF3CO)2O Me
m-CPBA CH2Cl2, 22 °C; NaBH4 H
N N
CH2Cl2, 22 °C Na2S4•H2O MeOH, 22 °C N
S
DMSO, 22 °C;
94% 62% O Me
O

D. J. Jansen and R. A. Shenvi, J. Am. Chem. Soc., 135, 1209 (2013)

Yokoshima Group - Group Meeting Problems 12/21/2019
1
TMS
O
N2 O Rh2(esp)2 (0.5 mol%) TBAF
O
O CH2Cl2, rt THF, 45 °C
O
O 71% 63%

J. A. May et al., J. Am. Chem. Soc., 134, 17877 (2012)

2
Pd(OAc)2 (10 mol%)
PCy3
O CsOAc
CS2CO3
I +
N N N
DMSO, 110 °C

82%

Y. Zhang et al., Org. Lett., 21, 6508 (2019)

3
1) Na2WO4•2H2O 3) Pd black
H2O2, toluene H
H2O, 0 °C to rt, 76% reflux, 56% N Me

N Me 2) allylmagnesium bromide 4) Raney-Ni, H2

H THF, 0 °C, 46% OH

S. Murahashi et al., J. Org. Chem., 55, 1736 (1990)

A. B. Holmes et al., Tetrahedron Lett., 36, 9047 (1995)

4
O O
1) BF3•OEt2
CH2Cl2, 80 °C
N 79% N

MeO MeO
2) toluene, 155 °C
N 96%
N N
NHTs
CO2Me CO2Me

A. M. Echavarren et al., J. Am. Chem. Soc., 138, 3671 (2016)

Yokoshima Group - Group Meeting Problems 01/11/2020

1
O

Me OH O
(C6F5)3B
Me
CH2Cl2, rt
N Me
Me Me 2
93%
Me

M. Brewer et al., Org. Lett., 22, 497 (2020)

2
1
Me R R1
Me
H Me
Me R1
Me Pb(OAc)4, I2, CaCO3 Me
+
H OH benzene, 85 °C
O R2
R2 O O
O O
Me R2 = H, 15% R2 = H, 52%
Me
R1 = R2 = I, 8% R2 = I, 10%
Me Me
P. Heretsch et al., J. Am. Chem. Soc., 142, 104 (2020)
 Yokoshima Group - Group Meeting Problems 01/29/2020

1
CO2Et
O CO2Et
Cl N
PhONa phenylhydrazine, TFA
N
N DMPU, 23 °C DCE, 40 °C;
EtO2C DNs TFA, Et3SiH, 23 °C N N H
70% H H
16% 67%

X.-S. Peng et al., J. Org. Chem., 85, 967 (2020)

2
cat. TFA
CHO CH2Cl2, rt;
+ MeO N TMS
Bn aq HClO4
80 °C N

V. S. Moshkin et al., Org. Lett., 22, 631 (2020)

3
Ph
NC CN PPh3 (0.3 eq.)
PhCO2Na (1.0 eq.)
+ •
CO2Me CN
toluene, 110 °C
Ph CN
H CO2Me
85%

Y. Huang et al., Org. Lett., 22, 433 (2020)

4
O
Me O
Me
Me PhI(OAc)2 KH O
O
allyl alcohol A 18-crown-6
Me
OH Me
CH2Cl2, rt THF, –78 °C THF, reflux Me
OMe
77% 76% 97% O CeCl2
H OMe A
O

C.-C. Liao et al., Org. Lett., 5, 4741 (2003)

5
Me
Me Me
Me methylene blue
O O2, hν Me H
Me H Me CO2H
OAc CH2Cl2, 0 °C to rt; H H
H H acetone/NaHCO3 aq. AcO
AcO H
H 73%

J. Gui et al., Angew. Chem. Int. Ed., 57, 3617 (2018)

Yokoshima Group - Group Meeting Problems 02/15/2020

1
Me Me
t-Bu SbF6
A (10 mol%) O
O A = MeCN Au P t-Bu
H
DCE, rt
H
Me 74% (dr = >20:1) Me

Z.-X. Yu et al., J. Am. Chem. Soc., 142, 2777 (2020)

2
OH OH
(COCl)2, DMSO
–78 °C;

Et3N O
N –78 °C to rt; N
Me aq. NH4Cl Me

67%

J. C. Menéndez et al., Synlett, 18, 2792 (2007)

3
1) t-butylsulfinamide, t-BuOK
Ph THF, reflux OMe
Me 2) MeOH (1.2 eq), AgOTf (10 mol%)
DCE, rt Me
MeO
Ph
N 3) DCE, 80 °C N
85% (3 steps) H
Ts S
t-Bu O

R. Fan et al., Org. Lett., 22, 823 (2020)

4
O O

Me Me
Ph Me Ph
Ph Me Ph
HO (1.3 eq) A (1.2 eq)
Ph 70% Ph
Ca(OTf)2 (10 mol%) Ph O
Ph Bu4NPF6 (5 mol%)
A DCM, 90 °C; Me
(1 eq)

S. Yaragorla et al., Adv. Synth. Catal., 360, 4422 (2018)

 Group Mee+ng Problems - 2020/05/16

1
1) KOCEt3 (3.0 eq)
OH O BF4 IPh
THF, −78 °C to rt O O
O 73% O H
+
2) Fe2(CO)9
Me benzene, 95 °C;
i-Pr DBU, 95 °C i-Pr Me
51%

C. M. Gampe and E. M. Carreira, Chem. Eur. J., 18, 15761 (2012)

2
OMe OMe
O OH
BCl3 (4 eq.)
O
Me CH2Cl2, 0 °C
Ph 71% Ph

L. P. Bejcek and R. P. Murelli, Chem. Commun., 56, 3203 (2020)

Pd(OAc)2 (10 mol%)

PPh3
MeO2C K2CO3 MeO2C
Br MeO2C
MeO2C DMF, 110 °C
OMe
32%

M. Schelper and A. de Meijere, Eur. J. Org. Chem., 582 (2005)

 Group Mee,ng Problems - 2020/05/23

1
O O
TMSCl H
H NaI, Et3N mCPBA (1.1 eq) H5IO6 O H
H OH
H MeCN, 50 °C hexane/CH2Cl2 THF/H2O, rt;
−15 °C to rt I2, NaHCO3 I N
NHCO2Me H CO2Me
rr = 6:1 OMPM
OMPM 50% (3 steps)
*rr = regioisomer ratio

Y. Morimoto et al., Angew. Chem. Int. Ed., 35, 904 (1996)

2
1) SmI2, HMPA
THF, 50 °C
OH 92% Me
2) DMPI, NaHCO3 O
O DCM, rt O OMe
Me 85% Me
OBz HO
H 3) K2CO3 H
OH MeOH, 65 °C Me
O O
Me 65%
Me Me
Me Me

H. Ding et al., Chem. Eur. J., 22, 959 (2016)

O O
TiCl4 (2.5 eq)
N
DCM, −78 °C to rt
H
N3
78%

S. Baskaran et al., Chem. Commun., 48, 5778 (2012)

 Group Meeting Problems - 2020/05/30

1
O O
Me O 1) TFAA, DMAP Me HO
TMSO DCM, 0 C Sc(OTf)3 TMSO Me
O Me tetracyclic O
H Me
compound
H OH 2) Zn, AcOH DMF, 80 C H
Me
TMSO DCM TMSO OTBS
OTBS
Me 62% Me

P. S. Baran et al., Nature, 532, 90 (2016)

n-Bu
Me Me

Me PtCl4 (5 mol%) Et
Et
Me toluene, reflux n-Bu
N
N OH
58% Et
Et

S. Ma et al., Chem. Commun., 53, 4722 (2017)

3
Me O
Me
O Si Me h mCPBA Me Si
tetracyclic HO
compound OH
hexane 56%

38%

C. S. Penkett et al., Org. Lett., 1, 2073 (1999)

 Keys to the Problems (05/16/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/05/16)

2
OMe OMe
OMe
O O
O
O O
Me Me O BCl2
BCl2 Me Cl
Ph BCl3 Ph
Ph
Cl

OMe OMe OMe

O O O
BCl2 BCl2 BCl2
O O O
Me Cl Me Cl
Ph Me Cl Ph Ph

CH3COCl

OMe OMe
O quench OH
BCl2

Ph Ph

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (05/16/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (05/23/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (05/23/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (05/23/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (05/23/2020)

Q3

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (05/30/2020)

N Me
CF3 O CF3 N
Me CF3 O
O O CF3 N
N O
O

O
Me O Me O
TMSO N Me O
O Me Me
TMSO
H OH CF3 N O Me
Me
TMSO OTBS H O CF3
O Me
Me TMSO OTBS O
Me

OAc
O Zn O Zn
Zn
O Me O Me O
Me O TMSO +H TMSO
TMSO O Me O Me
O Me O HCF3 H O CF3
H O CF3 Me Me
Me TMSO OTBS O TMSO OTBS O
TMSO OTBS O Me H
Me
Me

OAc
Zn O
OH OH
O Me CF3
O OH aqueous
Me CF3 TMSO O
work up
TMSO O O
O H MeMe
H MeMe TMSO OTBS
TMSO OTBS Me
Me
tetracyclic
compound

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (05/30/2020)

Yokoshima Group – Group Meeting Problems

 Ke eP be (05/30/2020)

2 .
⑦

÷¥E÷÷i
BY Pt

I
"
18.8kcal lmol
.
.

Me
.
.

ER ] I Pe ]
My
.
.

Me Ho

÷i÷±*
'

±. .

:O to

Me

hey ⑦ I Cpe ]
Me ←
~
Ee
* .
. .

a
-

I
/
Ee
E-

FT
Me

Mey I
yet

7.tkcallnol.tt
ETI
→ n .
Bu

Ee
→

Another route

⑦ ④
"

:
]
By
'
e

if
a- .

f-
"
.
.

me r
EE i
.

÷ →

⇒
FT
Me

Mey I
yet

na

Ee

Y a G G Mee P be
 Keys to the Problems (05/30/2020)

-------------------------------------------------------------------------------------------------------------------------------------------

Yokoshima Group – Group Meeting Problems

 Group Mee,ng Problems - 2020/07/04

1
Cu(OH)2 (10 mol%)
LiOMe O
O NNHTs H2O
Me Ph Me toluene, 100 °C Me
Ph
81%
1.0 eq 2.0 eq

Y. Jiang et al., ACS Catal., 10, 3664 (2020)

2
Me O Me OAc
H 1) N2H4, H2O, TFA Me
H
Me THF, 0 to 90 °C 3) hν, EtOAc, rt Me
HO HO H
O Me 2) Pb(OAc)4 4) TBAF O
OTBS CH2Cl2, 0 °C THF, 0 °C OH
Me O O
Me
Me 79% Me
52%

P. Li et al., Chem, 4, 2944 (2018)

3
O O O
CpPd(π-cinnamyl) (10 mol%)
i-PrOH (4 eq) Me H H
+ TsN
toluene, 120 °C Me
Me N -
Ts TsN H
68% 10%

Y. Wei and M. Shi et al., Chem. Commun., 54, 14085 (2018)

 Group Mee-ng Problems - 2020/07/11
1
O F
H
O F (4 eq) F
O
F EtAlCl2 (50 mol%)
O
F F
• DCM
F F H F
Me −78 °C to rt
F
83% (dr = 50:1) Me
M. K. Brown et al., Angew. Chem. Int. Ed., 59, 436 (2020)
2
Me Me
Me Ti(Oi-Pr)4
c-C5H9MgCl CSA (5.0 mol%) Me Me
N Me N + N
THF PhCl, µW (300W)
O 0 to 20 °C 140 °C

77% 68% (NMR) dr = 80:20

Y. Six et al., Chem. Eur. J., 19, 11759 (2013)

3
O OR
N
N N
HOCO2NH4 MeCN
O Et
Et H OEt
EtOH-H2O 50 to 70 °C N OAc
N OAc N OAc (R = H)
50 °C Me H CO Me
Me HO CO2Me (R = Ts) Me H CO Me 2
2 51%
76%

D. L. Boger et al., J. Am. Chem. Soc., 132, 13533 (2010)

4 D. L. Boger et al., J. Med. Chem., 56, 483 (2013)

Me Me
1) OEt Mo(CO)6, TFA
OH
H toluene, 55 °C MeCN-H2O, reflux; H H
N N
O 2) BzCl, DMAP, Et3N TFA, reflux;
O DCM, 0 to 23 °C benzene, reflux OBz
O (Dean-Stark)
Me CF3CO2
70%
V. G. Lisnyak and S. A. Snyder, J. Am. Chem. Soc., 142, 12027 (2020)

5
Me

DDQ (2.5 eq.) Me

Cu(OTf)2 (30 mol%)

DCM, 40 °C

71%

T. Jin et al., Org. Lett., 22, 5121 (2020)

 Group Mee*ng Problems - 2020/07/18
1
Me

Me
NCS, H2O
O Me THF, −18 to 0 °C; AlCl3 O
O
O N OMe
O OMe silica gel; toluene/Et2O
N Et3N, rt 95 °C HO
O2N
H
90%, single isomer 86%
O2N

dr = 1:1

D. Ma et al., J. Am. Chem. Soc., 140, 11608 (2018)

2
O
NH Me Me HN
HO LiOH HN
Me
Me H Me + Me H O
N H2O, rt
O O O
H NH HN
N N
O N O O

58% 5%

L. A. Lawrence et al., Nat. Chem., 12, 615 (2020)

3
O O 1) TsNHNH2
MeOH, rt O O O O
quant

• 2) NaH H
O toluene, reflux

54% 44%

M.-H. Baik, H.-Y. Lee et al., Eur. J. Org. Chem., 609 (2020)

4
Ph

0 °C
MeS S(O)Me 1.0 sec
in DCM (py)2IBF4 Ph
Ph SMe (80 mol%)
Tf2O in DCM SMe
85% N SMe DCE, 65 °C N
i-Pr2NEt + PhNH2 H
in DCM 84%
: micromixer

A. Nagaki, H. Yorimitsu et al., Chem. Lett., 49, 160 (2020)

 Group Mee-ng Problems - 2020/07/25
1
CF3
F
Br COMe OAc N
t-Bu
, N N
F
Ir[dF(CF3)ppy]2(dtbbpy)PF6 IrIII PF6-
NiBr2•3H2O F
N
4,7-dimethoxy-1,10-phenanthroline N
t-Bu
F
N N CF3
H2O-DMSO, blue LEDs COMe Ir[dF(CF3)ppy]2(dtbbpy)PF6
Boc Boc
cooling by fan MeO OMe

N N
84% 4,7-Dimethoxy-1,10-phenanthroline

D. W. C. MacMillan et al., Science, 352, 1304 (2016)

2
Me
Me
Me Me
Me t-BuOCl Me hν Me
DCM, −78 °C; Me
N Me Et3N
Me Me Me
N N N
Me Cl benzene Me
B
N C B Me N C
H , −78 °C 63% (brsm) H

60%

P. S. Baran et al., Nature, 446, 404 (2007)

3
Cl Cl

N
O
O IPrAuNTf2
HFIP N N
O
DCE, rt
O IPr
77%

H. Ohno et al., Org. Lett., 20, 4401 (2018)

4
1) SEMCl, i-Pr2NEt H
O DCM, 0 °C to rt H
100% t-BuPh, 150 °C
N OH N O + N O
2) Li(CH2)4CH=CH2 90% (A:B = 1.3:1)
DME, −40 °C;
OP p-TsOH, rt OP OP
84%
P = TBDPS A (major) B (minor)

N. Chida et al., Angew. Chem. Int. Ed., 58, 4381 (2019)

 Keys to the Problems (07/04/2020)

-------------------------------------------------------------------------------------------------------------------------------------------

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/04/2020)

AcO OAc
Me Pb OAc
Me Me N
N AcO OAc Pb OAc
Me N H H H N H OAc
N H
O
H Me N H
HO H Me HO H
Me
Me
O O O Me O OAc
H CF3 OTBS
O O OTBS O
Me Me
H O
Me Me
F3 C

OAc
H
AcO H OAc
Me OAc Me OAc Me NH OAc
N N
H Pb OAc H H N Pb OAc
N N Pb OAc
OAc OAc
HO H Me HO H Me OAc HO H Me
Me Me O Me
O O
OTBS OTBS O OTBS
Me O Me O Me
Me Me Me

OAc OAc OAc

AcO H Me N Me
Me N H N H
H N
Me h Me
HO H HO H
HO H Me O Me Me
Me N2 O
O AcOH OTBS OTBS
OTBS Me O O
O Me
Me Me Me
Me

Me OAc Me OAc
Me Me
H H
Me TBAF Me
HO H HO H
O O
OTBS OH
Me O Me O
Me Me

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/04/2020)

3
O
O O

Pd(0) Pd
Pd
Me N
Me N Me N Ts
Ts Ts

Pd(0)

O O O O
H H H
Me H H Me Pd Pd
Pd Me Me
TsN TsN
TsN TsN

H H
H
minor product

iPrOH

O
O OH
H OiPr
OiPr
Me H O Pd +H+
iPr Me H Pd
Pd Me H
TsN H - TsN
TsN H
H
H
H

OH O O
OiPr OiPr
Pd Pd
iPrOH
Me H Me H Me H
TsN TsN TsN
H H H
O Pd OiPr

H
+H + - -H H Pd OiPr Pd(0) + iPrOH
H
elimination +
acetone

O
O

Me H Me
TsN
TsN
H

main product

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/11/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/11/2020)

H H
O

OTs OTs OTs OTs

N N N N OH
HOCO2NH4
O Et O Et OH Et OH Et
EtOH-H2O
N OAc 50 °C, 24 h N OAc N OAc N OAc
Me H Me H H H
CO2Me CO2Me Me CO2Me Me CO2Me

path 1
O
H H
OTs OTs O
NH O N
N OH

OH Et H Et
OH Et
N N OAc
N OAc OAc
H Me H Me HO CO2Me
Me CO2Me CO2Me

path 2

OTs OH O
N N
N OH

OH Et H Et
OH Et
N OAc N OAc
N OAc
Me H Me HO CO2Me
Me H CO2Me
CO2Me

OH OH OH
N N N
MeCN
O Et O Et OH Et
50 to 70 °C
N OAc N OAc N OAc
Me H Me H Me H
CO2Me CO2Me CO2Me

N N N

O Et OH Et OH Et
N O-H insertion N N
OAc OAc OAc
Me H Me H Me H
CO2Me CO2Me CO2Me
singlet carbene

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/11/2020)

Me Me
4
OH OH
H H H
N N
O O
O O
O EtO O
OEt Me Me

Me
N
N
Ph Cl Cl Me
Ph N
O
N
O

Me
Me
Me
N H OBz
OH H H
H H Me
Ph N N
N O
O O
O
O EtO O
EtO O Me
Me

Me Me Me

OBz OBz OBz

H H H H H H
Mo(CO)6
N N N
O O O
O O [Mo]
[Mo] EtO O
EtO O EtO O O
Me Me Me

Me
Me
Me
OBz
OBz H H
OBz H H
H H H N
+H N H O
N H O
O EtO O
[Mo] EtO O O
EtO O O H [Mo] Me
O [Mo] Me
Me Sol
Sol
Sol
Solvent Sol : Solvent

Me

OBz
H H
N
H O
O
O
Mo(II) Me

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/11/2020)

Yokoshima Group – Group Meeting Problems

 Ke eP be (07/11/2020)

5.

"

武 鎛が と
殲-
翹へ
い
一

0
0
0
奭 熱 魑 .
に

Nellie Nate
Clive
ce.it a
と いい
[Cu]
6 aP-

[や「 (金 介
」
一

-
Me
(盛 行
一

1
-
Me
aryl Migration Hれ
SET 12
\ /
-
.

_
m

ft -
-

-
> est 1 \ヘ =

f)
1
も粗
- 、
に
趙 or
たい
\ 氏 t seen
u

や「
OH OH 」

ル、 _ ce N いき 、 a

て
-
Me
た い = と
「
主に
「

b 面
は
6 が 。
_

Y a G G Mee P be
 Keys to the Problems (07/18/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/18/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/18/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/18/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/18/2020)

––––––––––––––––––––––––––––––––––––––––

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/25/2020)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/25/2020)

2
Me Me Me
Me Me Me

Me Me Me
N N N
C N Cl N Cl
N
H H
B

Cl
O O

Me Me Me
Me Me Me

Me Me Me
Me Me
N N Me N Me
Cl hν
N N Cl N Cl
B B B

Me Me Me
Me Me Me

Me Me Me
Me Me Me
N N N
Me Me Me
N Cl N H Cl N
H Cl
B B B

Me Me
Me Me

Me Me
Me Me
N N
Me Me
N N C

B H B

NEt3

Me
Me

Me Me
Me Me
N
Me
H 2O Me
N C Me
workup N
B Me
H
N C
O H
H

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/25/2020)

3 Cl Cl

O O
N N
O O Cl O O Cl
[Au]
Cl

[Au] [Au] –
N
Cl

[Au]

O O
O O

+[Au]
[Au]

O [Au] O
O
O
[Au]

5-endo [Au]
cyclization

O O O O

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (07/25/2020)

Q4

Yokoshima Group – Group Meeting Problems

 Group Meeting Problems - 2020/08/22

1
N2 OH O NO2
Rh2(OAc)4 (4 mol%)
NTs +
N toluene, 85 °C N
Me O2N Me
60%

X. Bao et al., Adv. Synth. Catal., 362, 1292 (2020)

2
O
O OAc
PCC
Me PTSA silica gel Me O
hexacyclic Me
Me H
H O compound
N benzene DCM N
reflux 0 °C to rt
O O
85% quant.

H. Zhai et al., Angew. Chem. Int. Ed., 57, 947 (2018)

3 NO2
OH O
O Br [RhCl(CO)2]2 (5 mol%)
O
CO
O Br
1,2-DCE, 85 °C
NO2 95% O

J. Gong and Z. Yang et al., Nat. Commun., 5, 5707 (2014)

 Keys to the Problems (2020/08/22)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/08/22)

Yokoshima Group – Group Meeting Problems

 Ke eP be (2020/08/22)

攤
黜: RO

が
出
で駲 灤
で -

だい

i
ifs 蘭
Rrnx
だい
-

Y a G G Mee g P be
 Keys to the Problems (2020/09/05)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/09/05)

NN NN

t-Bu t-Bu

O t-Bu
t-Bu O

O
t-Bu N
N N
t-Bu t-Bu
t-Bu t-Bu t-Bu t-Bu
N
N N

N
t-Bu t-Bu
N

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (09/05/2020)

3
Br
OH O O
K2CO3
Ph Ph Ph

compound A

O O

N N
Cl
O O N
N N Cl
H Cl H
N-chloroamine
N-chloroammonium salt

Ru(II) compound A

hν *Eox = – 0.81 V
(vs. SCE)
*Ru(II) Ru(III)

H N O
TFA N H
N N
SET Ph
Cl Cl H

N-chloroamine N-chloroammonium salt

Ered = – 1.80 V Ered = + 0.43 V
(vs. SCE) (vs. SCE)

SH2

N O basic
work-up N O
Cl H
Ph Cl N
Ph
Cl H

β-chloroamine
I

O N
N O
N O Ph
Cl in polar solvent I Ph
Ph

H H
Al
H H
N
O
O
N Me
Ph
Ph

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/09/19)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/09/19)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/09/19)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/09/19)

H H
H2

cat. PtO2
H H H H H H
semibullvalene

Yokoshima Group – Group Meeting Problems

 Group Meeting Problems - 2020/10/03

1
1) DIBAL
CH2Cl2, 78 °C OH OH
N SiPhMe2 Cu(acac)2 88% H

N2 toluene, 85 °C 2) Hg(O2CCF3)2 N
O AcOH, TFA, CHCl3, rt;
58%
AcOOH, 0 °C to rt
81%
J. A. Vanecko and F. G. West, Org. Lett., 4, 2813 (2002)

2 S

O Cu(OAc)2 1) KOH O
NaOAc EtOH, 80 °C
N C20H20N2O4S O
H
DMSO, rt 2) TsOH
N O toluene, 120 °C S
47%
C16H14N2O2 62% (2 steps)

H.-X. Dai et al., Org. Lett., 21, 5981 (2019)

Ph
3 Me
NH
1) i-PrOH, 90 °C;
NaOH aq, rt O H Ph
N 85%
+ Cl Me N
O2N 2) o-dichlorobenzene
200 °C (MW)
OTIPS
OTIPS 84%
NO2

C. D. Vanderwal et al., Tetrahedron Lett., 56, 3165 (2015)

 Keys to the Problems (2020/10/03)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/10/03)

-------------------------------------------------------------------------------------------------------------------------------------------

-------------------------------------------------------------------------------------------------------------------------------------------

Yokoshima Group – Group Meeting Problems

 Ke eP be (2020/10/03)

-
に 「
3 ×
Ph
R [ cos
Ph

觱 龐
-

Rii 智
「
超 R - i
°
'

ニ
、
々
橋
H
斷 を
斷 進 で

1 1 I
NO2 NO2 NO2

Ph
R
無結に苾
=
F
←>
々

湜鹵稲置 蹬
ど
の
1
に
両
1 心 me-inme~ty.me
ar me

に R

, i
NO2 NO2

est Meant※科 と
→ meant※熈 ? minato
k R k R k
-
1
Zinc ke Aldehyde
m
p T
m
澪
、
も 。
竺吹
灬
、
一
嘯。 一味
the the
。

ITR
or

Gelato cyclic

間 es 間n
い、
④
。
。
ri
the the
in
T)
潘
/ DieIs Alden
-

靍
が
・

OTIPS OTIPS

Y a G G Mee P be
 Keys to the Problems (2020/10/10)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/10/10)

[Au]
OBn
[Au]

R R
OBn OBn

[Au] [Au]

O BnO
R

H H
BnO [Au] BnO [Au]

H
OBn

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/10/10)

3
O
O O
· O
Cl
H N
N
C O H NEt3
O
Et3N N
N
O

O O
O O
N O
N
N N
O H

Et3N

O O
Me3OBF4
O O
N O O
MeNO2; N
N N

CH3
O
Me Me
O O
O O
N O N O
N N
Me Me

O O
O O H
O N O N O
Me
Me N N N N
H
H O Me
O

H H
O O
NaBH(OAc)3

0 °C to rt N N N N
Me H Me
O O
(AcO)3B H O (AcO)3B H O

H H
O O
work-up
N N N N
H Me H
O OH Me
O O

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/11/07)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/11/07)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/11/07)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/11/07)

4

Step 1
H OMe
• •
+e– +e–

N N N N N
H H H H H
H OMe

Step 2

X
X2Bi
X2Bi
O O BiX2 H BiX2
HO O

N N
H H
N
H
X
H X H

N N N N
H H H H
H
X

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/01/16)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/01/16)

3
O O
O
Cu(OAc)2⦁H2O [Cu] Me N-H insertion
N2 Me Me
NTs N
NHTs Ts
H step 1

HO [RhⅠ]
Ph MgBr MgBr
HO Ph [RhⅠ] O Ph
O O Ph workup
Me Me
Me Me N –H2O
N N
N Ts
Ts Ts
Ts step 2

O Ph O Ph O Ph
[RhⅠ] Oxidative Reductive H
Addition H Elimination
H N Me [RhⅢ] N Me [RhⅠ] N Me
O O O
S S S
O O O
Me Me Me

O Ph
O [RhⅠ] O Me
Me N O [RhⅠ] O Me
O S N
[RhⅠ] N Me H O S
O ＜ Me
S Ph
O Me Ph
H
Me pseudo-axial pseudo-equatrial

[RhⅠ]O Ph HO Ph
Me Me workup Me Me

N N
S S
O O O O

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/01/16)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/01/16)

5
N(n-Bu)4
Me O O
O O
N(n-Bu)4 Me Si I
I
Me
F

TMS-EBX

N(n-Bu)4 O O
O O N(n-Bu)4 O
O
I H Boc O Boc O
N N
O O
BocN N BocN N Me
Si t-Bu
OTBS O
Me
F N(n-Bu)4

N(n-Bu)4
O
N(n-Bu)4 O
O N(n-Bu)4
Boc O
N O R Boc I
I N
R
BocN N
BocN N CO2
O N(n-Bu)4
O — I
O
N(n-Bu)4

N(n-Bu)4
N(n-Bu)4 O
Boc H Boc NHBoc
N N O O
OR OR
BocN N
BocN N 1,2-hydride BocN N work-up O
O shift O
O
O O

OBn
Li
Li Li n-hexyl
O
H Boc Boc
n-BuLi N
n-Bu N OR
OR
THF, –78 °C; BocN N
BocN N O
O
O O

Li Boc Boc OR
Boc N OR N
N DMPU
OR H O
BocN N O BocN N H
BocN N O n-hexyl
n-hexyl n-hexyl
O OBn
OBn O OBn
O O
O O
Li

Boc Boc
OR
Boc N
OR BocN N
N H O
–H+
H OH BocN N
BocN N n-hexyl N OR
+H+ n-hexyl
n-hexyl H H O
O OBn BnO2C
O OBn O O
O

Boc
BocN N

n-hexyl N OR
work-up
H H O
BnO2C
O

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/02/13)

1
R R
(R = CO2Et)
Me N Me
H
blue LED
H H IrIII*
R R

HO Ph
O Me N Me HO Ph Ph
H
IrII IrIII
Ph Ph Ph
N
e N O S
N
SO2Ph O
SO2Ph

R R R R

Me N Me Me N Me
H H

HO Ph
HO Ph HO Ph
Ph Ph HAT
Ph
N
– SO2 N
S Ph N Ph
O
O

R R R R

R R Me N Me Me N Me
(R = CO2Et) H
Me N Me
H
blue LED
IrIII*

HO Ph IrII IrIII HO Ph spin-center

Ph Ph shift (SCS)

e –H2O
N Ph N Ph
H

H H R R
R R
R R

Me N Me Me N Me
Me N Me H H
H

Ph Ph
Ph HAT Ph

N Ph N Ph
H

R R R R

Me N Me Me N Me
H

HAT: hydrogen atom transfer

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/02/13)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/02/13)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/02/13)

瀅 醼黔 瓚
で で ・

一
職 HE
、

国IT
の

ne Me
OH ME 男に u Me

黔藩 璘 一
の

職梁 藩灤
t
職 Me
。 で 。

聹欝
i.

が
・
ー い
一
勲
-

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/03/06)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/03/06)

2
Step 1

Step 2

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/03/06)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/03/06)

* Selectivity of 1,7-H Shift

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2020/03/06)

5
Step 1 O2
hν Ru(II)
O
O •
O
Ru(II)* Ru(I)
O
NTs • NTs NTs

N N N
H H H

O •O O O
O NTs NTs NTs
NTs
N N O N O N
H H • H H O

Step 2
H2NPh
O NHPh NHPh
+H+
NTs NTs NTs
–H2O
N N N
H O H O H OH

NHPh NHPh NHPh

H
–H+
NTs NTs NTs
N N N
H OH

Yokoshima Group – Group Meeting Problems

 Group Meeting Problems - 2021/04/10

1
O Ph
PhSH
O
Br DCE, rt
Ph
N N SPh
H 93%

W. P. Unsworth et al., Org. Lett., 23, 2063 (2021)

 Group Meeting Problems - 2021/04/10

2 OBn OBn
1) EtAlCl2 BnO
OBn
DCM/THF, 40 °C H
CHO
H
2) TPP, O2, h
O CDCl3 rt; O
TMS
Ac2O, Pyridine, DMAP

43% (2 steps)
T. Luo et al., J. Am. Chem. Soc., 141, 20048 (2019)
 Group Meeting Problems - 2021/04/24

6 Ph
Ph O
O 1) CHCl3, 40 ℃ Ts
O N
O O
Ts 2) TFA, DCM, 40 ℃
N OMe O Ph
H Ph
O 77% (2 steps)

N. C. O. Tomkinson et al., Org. Lett., 22, 1659 (2020)

 Group Meeting Problems - 2021/04/24

7
NOBF4
O
TBSO tBu N tBu TFA
Tricyclic compound
MeCN, 30 °C DCM, 90 °C
N O
C10H15NO2
H
91% 87%

Y.-Q. Tu et al., Angew. Chem. Int. Ed., 57, 13192 (2018)

 Keys to the Problems (2021/04/10)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/04/10)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/04/14)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/04/14)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/04/14)

5
OH
HO HO Bn Bn O
NH N N H
O HO
Bn
+H+
H
–H+ CO2Et CO2Et
CO2Et

CO2Et CO2Et CO2Et

Bn O
N Bn
N
AuCl3
O
–H2O CO2Et
CO2Et
[Au] CO2Et
CO2Et

Bn Bn Bn
N N N
O
CO2Et CO2Et
CO2Et [Au] CO2Et
[Au] O [Au] O
CO2Et CO2Et

H
Bn BnN
N
CO2Et
CO2Et
CO2Et O CO2Et
O

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/04/24)

6 O
O
O
O O O
O
O O O O
Ph Ph
Ph O
Ph Ph
Ph

H
O
N OMe
Ts O O
O Ph
O O Ph
Ph
Ph
O Ph N O
Ts
N OMe
Ph Ts OMe
O
Ph
H
O Ph O Ph
O N Ph
+H+ -H+ O
Ph Ts O
Ph N
+H+ OH
N O Ts O
Ts H2 O H
OMe

Ph
+
-H Ph O
N
Ts O

Yokoshima Group - Group Meeting Problems

 Keys to the Problems (2021/04/24)

7
Step 1 : Semipinacol Rearrangement

TBS O TBS O
OTBS

N O N O
N O

BF3
F
OTBS O OH
Si
O O O
N N N
H

tBu tBu

N H N

tBu tBu

Step 2 : Beckmann Rearrangement

H O

OH OH2
O O O O
N N N N N
H2 O
O
O O

N OH H
N O N O
H
H H
H

Yokoshima Group – Group Meeting Problems

 Group Meeting Problems - 2021/05/08

2
OH Pd/C OH
t-BuOLi
+ HO 4 4
toluene, 160 C
2 eq.
80%

H. Zeng et al., Angew. Chem. Int. Ed., 60, 4043 (2021)

 Group Meeting Problems - 2021/05/12

3
N Br OTf
nPr O
HO
O O 4-pyrrolidinopyridine m-CPBA
O
i-Pr2NEt tricyclic Na2HPO4 TMSOTf (0.15 eq)
compound
DCM, rt DCM, rt benzene, rt
O
O 85% 74% 56% O

D. Romo et al., J. Am. Chem. Soc., 130, 10478 (2008)

 Group Meeting Problems - 2021/05/12
1) IPrAuNTf2 OH
O
4 NHMe DCE, rt

O 2) blue LED ( max = 465 nm)

AcOEt, rt OHC
NMe
80% (2 steps)

Y. Liu et al., Org. Lett., 23, 1090 (2021)

 Keys to the Problems (2021/05/08)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/05/08)

2
H
HO 4 O 4
0 ll
Pd Pd H2

tBuO

OH OH OH O O
H+ H

H H +H+
ll
H Pd0 PdllH2 Pd0
HPd ll
Pd H H
Reductive
Elimination

tBuO

O O O OH O OH
+
H
H +H
4 4 4

HPdll HPdll
O H O H O O
PdllH
4 4 4 4
H2O ll
Pd H2
-H Elimination

OH OH O O
H+ H+
4 4 4 4
+
+H H HPd ll +H+ HPd ll
Pd H2ll
0 Oxidative
Pd Addition -H Elimination

OH
H+
4
+H+

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/05/12)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/05/12)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/05/22)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/05/22)

Yokoshima Group – Group Meeting Problems

 Group Meeting Problems - 2021/06/05
1
H H
1) O2, rose bengal, MeCN
500 W tungsten lamp, 30 °C O
O
O
H H 2) O2, Cu(OTf)2 (cat), MeCN, 20 °C H H
OMe O
3) TsOH (cat), CH2Cl2, 0 °C to rt
O O
25% (3 steps)

J. S. Yadav et al., Tetrahedron, 66, 2005 (2010)

 Group Meeting Problems - 2021/06/12

2 PhI O OBn
Pd(PPh3)4 (5 mol%)
HO OBn
CO (200 psi), CO2 (200 psi) O
O O
O Et3N, 100 °C Ph
O
77%

K. C. Nicolaou et al., Angew. Chem. Int. Ed., 46, 4708 (2007)

 Group Meeting Problems - 2021/06/12

OBz
3 OAc t-Bu
t-Bu P Au NCMe SbF6 OBz
(5 mol%)
O OH

THF/H2O, –10 °C
O H
73%
H 97% ee, dr = 3:1
98% ee
E. M. Carreira et al., Angew. Chem. Int. Ed., 58, 2490 (2019)
 Group Meeting Problems - 2021/06/19
1) Copper cat 1 (6 mol%)
4 Me2PhSiH (2 eq)
NaOTMS (2 eq)
OBn BrettPhos (6 mol%) O
Ar2
[Pd(cinnamyl)Cl] 2 (3 mol%) CN O P
THF, 45 °C CuOAc
+ O P
OBn Ar2
2) n-OctO2C CO2n-Oct
Ph O Ph O
Toluene, 110°C
Ar = 3,5-(t-Bu)2-4-MeOC6H2
N
Br 73% (2 steps), er 99:1
Copper cat 1

S. L. Buchwald et al., J. Am. Chem. Soc., 141, 18668 (2019)

 Group Meeting Problems - 2021/06/19

5
Ti(Oi-Pr)4 (1.0 eq)
c-C5H9MgCl (2.0 eq) Me Ph
PhMe2Si
toluene, ｰ 78 to ｰ 30 °C;
OH
Ph SiMe2Ph
compound A (3.3 eq) Ph
Et2O, ｰ 78 to ｰ 30 °C OPMB

57% PMBO OLi Me

Ph
compound A

G. C. Micalizio et al., J. Am. Chem. Soc., 134, 2766 (2012)

 Group Meeting Problems - 2021/06/26

6 PivONH3OTf (2.5 eq)

FeCl2 (10 mol%) O
SH bpy (10 mol%) S
NH2
Me CH3OH:CH2Cl2 3:1
rt, 16 h Me

88%

B. Morandi et al., Angew. Chem. Int. Ed., 60, 758 (2021)

 Keys to the Problems (2021/06/05)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/06/12)

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/06/12)

3
OAc
O O Au OAc
O O
R R
R •
Au R
Au H
Au
O O
O
O
R = (CH2)3OBz
H H
H
H

AcO AcO AcO

AcO
R H R R
R
Au Au
Au – Au

H
H O O O
O

H H H
H

H 2O
O H
O Au
O Au O R O
R O O O
Au R
Au O O –H –H
R HO

+H
O H
Au H
H
H

O R OH Au
+H OAc H
– Au OAc O
R
R Au
O
H H

Yokoshima Group – Group Meeting Problems

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Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/06/19)

ClMg ClMg
i-PrO i-PrO i-PrO i-PrO
i-PrO Ti Oi-Pr i-PrO Ti Oi-Pr i-PrO Ti i-PrO Ti
Oi-Pr H
H

i-PrO Oi-Pr i-PrO Oi-Pr Ph SiMe 2Ph

Ti i-PrO Oi-Pr
Ti Ti
ー Ph SiMe 2Ph

PMBO OLi Me
Ph
Me
Ph
O OPMB
i-PrO i-PrO Ti
Ph SiMe 2Ph

Ph SiMe2Ph
i-PrO i-PrO
Ti SiMe2Ph Ti Ph
O < O
Me Me
OPMB OPMB
Ph Ph

Ph
(i-PrO)2 MO Ph
i-PrO O
i-PrOM PhMe 2Si Ti
PhMe 2Si Ti Me
Me
Ph
Ph
OPMB
OPMB

PhMe 2Si PhMe 2Si

Ph Me Ph Me Me Ph
PhMe 2Si
H
PMBO i-PrO Ti PMBO i-PrO Ti OH
Ph Ph Ph
i-PrO i-PrO
O O OPMB
M M

Yokoshima Group – Group Meeting Problems

 Keys to the Problems (2021/06/26)

Yokoshima Group – Group Meeting Problems