Cyclohexadienones

Palladium-Catalyzed Reactions of Cyclohexadienones: Regioselective Cyclizations
Triggered by Alkyne Acetoxylation
Rodolfo Tello-Aburto and Andrew M. Harned*
University of Minnesota, Department of Chemistry, 207 Pleasant Street SE, Minneapolis,

MN 55455
SUPPORTING INFORMATION
Table of Contents S1
Materials and Methods S2
Preparation of Substrates S3
General Procedure for Pd-Catalyzed Cyclization Reactions S14
Cyclization Products S14
References S21
Copies of NMR spectra S22
S1
Materials and Methods. Unless otherwise stated, reactions were performed in flame-
dried glassware under an argon or nitrogen atmosphere using dry, deoxygenated solvents.
Solvents were dried by passage through an activated alumina column under argon.
Palladium acetate (Pd(OAc)2) and PdCl2(PPh3)2 were purchased from Strem.
Iodobenzene diacetate (BAIB) and [Bis(trifluoroacetoxy)iodo]benzene (PIFA) were
purchased from Acros. Tetrabutylammonium tribromide1 and PdCl2(PCy3)22 were made
according to literature procedures. Acetic acid was distilled from acetic anhydride/CrO3
prior to use. All other compounds were purchased from commercial sources and used as
received, unless otherwise specified.
Thin-layer chromatography (TLC) was performed using plates precoated with silica gel
XHL w/ UV254 (250 µm) or alumina W/ UV purchased from Sorbent Technologies and
visualized by UV light, KMnO4, or anisaldehyde stains, followed by heating. ICN Silica
gel (particle size 32-63 µm) was used for flash chromatography.
1
H and 13C NMR spectra were recorded on a Varian Inova 300 (operating at 300 MHz
and 75 MHz respectively) or Varian Inova 500 (operating at 500 MHz and 125 MHz
respectively), and are reported relative to residual solvent peak (δ 7.26 and δ 77.2 for 1H
and 13C in CDCl3, δ 7.16 and δ 128.0 for 1H and 13C in C6D6, respectively). Data for 1H
NMR spectra are reported as follows: chemical shift (δ ppm) (multiplicity, coupling
constant (Hz), integration). Spectra obtained are described using the following
abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. IR spectra
were recorded on a MIDAC corporation M series spectrometer and samples were
prepared by evaporation from CHCl3 or CH2Cl2. High resolution mass spectra were
obtained from the University of Minnesota Mass Spectrometry Facility.
S2
Preparation of Substrates
OH Me O
HO , PIFA Me
0 ºC
Me O
Me
4-(but-2-ynyloxy)-4-methylcyclohexa-2,5-dienone (2a)
A well-stirred solution of p–cresol (108.14 mg, 1.0 mmol) in 1 mL of 2-butyn-1-ol was

cooled to 0 ºC and treated with PIFA (516.03 mg, 1.2 mmol, 1.2 equiv.) in one portion.
The reaction mixture was stirred at the same temperature for about 15 min. after which it
was diluted with water (20 mL) and CH2Cl2 (30 mL). The mixture was washed with 10%
NaOH (1 × 30 mL), and brine (1 × 20 mL), and concentrated under reduced pressure. The
residual crude product was purified by FCC using 9:1 Hexane/Ethyl acetate to give 110.4
mg of the title compound as white solid (68 % yield).
IR (neat) 2975, 2865, 2358, 2323, 2240, 1670, 1632, 1606, 1382, 1307, 1083, 1033,
1000, 864.4 cm-1
1
H NMR (300 MHz, CDCl3) δ 6.82 (d, J = 10.1 Hz, 2 H), 6.29 (d, J = 10.1 Hz, 2 H), 3.94
(q, J = 2.3 Hz, 2 H), 1.83 (t, J = 2.3 Hz, 3 H), 1.46 (s, 3 H)
13
C NMR (75 MHz, CDCl3, DEPT) δ C 184.9, 83.2, 75.5, 72.8; CH 151.0 (2), 130.2 (2);
CH2 54.2; CH3 26.3, 3.6.
HRMS (ESI+) 199.0735 calc for C11H12NaO2 found 199.0730
OH O
Me
BAIB, HO
Me
Me 0 ºC Me
Me Me O
4-(but-2-ynyloxy)-3,4-dimethylcyclohexa-2,5-dienone (2f)
A mixture of 3,4-dimethylphenol (153.0 mg, 1.25 mmol) and 2-butyn-1-ol (3 mL) was
cooled to 0 ºC and treated with BAIB (404.7 mg, 1.25 mmol). The mixture was stirred at
the same temperature for about 30 min and then concentrated under reduced pressure.
Residual product was purified by FCC using 9:1 hexanes/ethyl acetate to give 101.1 mg
(42% yield).
IR (neat) 2983, 2921, 2859, 2360, 2333, 2243, 1670, 1635, 1439, 1387, 1294, 1081, 1038
cm-1
1
H NMR (300 MHz, CDCl3) δ 6.79 (d, J = 10.0 Hz, 1 H), 6.25 (dd, J = 10.0, 1.9 Hz, 1
H), 6.15 (bs, 1 H), 3.83 (dq, J = 14.4, 2.3 Hz, 1 H), 3.70 (dq, J = 14.4, 2.3 Hz, 1 H), 1.99
(s, 3 H), 1.81 (t, J = 2.3 Hz, 3 H), 1.42 (s, 3 H).
13
C NMR (75 MHz, CDCl3, DEPT) δ C 185.4, 160.0, 83.1, 75.0, 74.8; CH 151.5, 130.1,
129.2; CH2 53.9; CH3 25.7, 18.0, 3.7
S3
OH O
Me
Me Me Me
BAIB, HO
0 ºC
Me Me O
4-(but-2-ynyloxy)-2,4-dimethylcyclohexa-2,5-dienone (2e)
A mixture of 2,4-dimethylphenol (152.4 mg, 1.25 mmol) and 2-butyn-1-ol (2.5 mL) was
cooled to 0 ºC and treated with BAIB (404.7 mg, 1.25 mmol). The mixture was stirred at
the same temperature for about 30 min and then concentrated under reduced pressure.
Residual product was purified by FCC using 9:1 hexanes/acetone to give 113.6 mg (47%
yield).
IR (neat) 2980, 2923, 2858, 2363, 2333, 2238, 1672, 1645, 1445, 1076, 1033 cm-1
1
H NMR (300 MHz, CDCl3) δ 6.75 (dd, J = 10.1, 3.2 Hz, 1 H), 6.52–6.56 (m, 1 H), 6.24
(d, J = 10.1 Hz, 1 H), 3.88 (q, J = 1.8 Hz, 2 H) , 1.87 (d, J = 1.4 Hz, 3 H), 1.79 (t, J =
1.8 Hz, 3 H), 1.40 (s, 3 H).
13
130.2; CH2 54.1; CH3 26.6, 15.8, 3.8
OH O
Me
Br Br Me
BAIB, HO
0 ºC
Me O
Me
2-bromo-4-(but-2-ynyloxy)-4-methylcyclohexa-2,5-dienone (2b)
A mixture of 2-bromo-4-methyl-phenol (0.12 mL, 1.0 mmol) and 2-butyn-1-ol (2 mL)

was cooled to 0 ºC and treated with BAIB (322.0 mg, 1.0 mmol). The mixture was stirred
at the same temperature for about 10 min and then concentrated under reduced pressure.
Residual product was purified by FCC using 9:1 hexanes/ethyl acetate to give 148.2 mg
(58% yield).
IR (neat) 2982, 2920, 2857, 2241, 1674, 1079 cm-1
1
H NMR (300 MHz, CDCl3) δ 7.29 (d, J = 2.9 Hz, 1 H), 6.82 (dd, J = 10.1, 2.9 Hz, 1 H),
6.38 (d, J = 10.1 Hz, 1 H), 3.96 (q, J = 2.3 Hz, 2 H) , 1.81 (t, J = 2.3 Hz, 3 H), 1.46 (s, 3
H).
13
128.8; CH2 54.8; CH3 26.2, 3.8.
HRMS (ESI+) 276.9840 calc for C11H11BrNaO2 found 276.9835
S4
OH OTBS
Br TBSCl, DMAP, Br
Imidazole
CH2Cl2, rt
O H O H
S1
3-bromo-4-(tert-butyldimethylsilyloxy)benzaldehyde (S1)
A well-stirred solution of 3-bromo-4-hydroxy benzaldehyde (1.94 g, 9.65 mmol) in 75

mL of dry CH2Cl2 was treated with imidazole (2.62 g, 38.6 mmol), DMAP (58 mg, 0.48
mmol), and TBSCl (1.74 g, 11.58 mmol). The mixture was stirred at room temperature
for 16 hrs and then diluted with 50 mL of CH2Cl2 and washed with 30 mL of NH4Cl
saturated solution, and 30 mL of brine. Organic layer was dried over Na2SO4, filtered and
concentrated in rotavapor. The title product (2.69 g, 88% yield) was obtained after
purification by FCC using 95:5 hexanes/ethyl acetate.
IR (neat) 2955, 2888, 2860, 1699, 1588, 1475, 1374, 1306, 1191, 1041, 919.1, 801.3,
800.5 cm-1
1
H NMR (300 MHz, CDCl3) δ 9.83 (s, 1 H), 8.07 (d, J = 2.1 Hz, 1 H), 7.71 (dd, J = 8.3,
2.1 Hz, 1 H), 6.96 (d, J = 8.3 Hz, 1 H), 1.05 (s, 9 H), 0.30 (s, 6 H)
13
C NMR (75 MHz, CDCl3, DEPT) δ C 189.8, 158.3, 131.3, 116.5, 18.5; CH 135.3,
130.4, 120.1; CH3 25.7 (3), -4.0 (2)
H
OTBS Br
OTBS
Br Br
Znº, TiCl4
H
THF, 0 ºC
O H HO
S2
1-(3-bromo-4-(tert-butyldimethylsilyloxy)phenyl)but-3-yn-1-ol (S2)
A well-stirred solution of activated zinc dust (622.0 mg, 9.51 mmol) in 25 mL of dry
THF was cooled to 0 ºC and treated with propargyl bromide (1.4 mL of a 80% wt
solution in toluene, 9.51 mmol), followed by TiCl4 solution (0.16 mL of a 1 M solution in
CH2Cl2, 0.16 mmol). The mixture was stirred for about 5 min. before a solution of
aldehyde S1 (1.0 g, 3.17 mmol)in 30 mL of dry THF was added. The reaction mixture
was stirred at the same temperature for 1 hr and then diluted with 50 mL of Et2O, and
washed with 30 mL of NH4Cl saturated solution and 30 mL of brine. Aqueous layer was
back-extracted with Et2O (2 × 30 mL). Combined organic layer was dried over Na2SO4,
filtered, and concentrated in rotavapor. Purification by FCC using 9:1 hexanes/ethyl
acetate afforded 1.03 g (92% yield) of the title compound.
S5
IR (neat) 3394, 3302, 2930, 1601, 1494, 1256, 1044, 914 cm-1
1
6.84 (d, J = 8.4 Hz, 1 H), 4.78 (td, J = 6.4, 2.2 Hz, 1 H), 2.60 (dd, J = 6.4, 2.6 Hz, 2 H),
2.38 (bs 1 H), 2.08 (t, J = 2.6 Hz, 1 H), 1.03 (s, 9 H), 0.24 (s, 6 H)
13
120.1; 80.5, 71.5; CH2 29.6; CH3 25.8 (3), -4.0 (2)
OTBS OTBS
Br Br
Et3SiH, BF3•OEt2
H H
CH2 Cl2 , 0 ºC
HO
S3
(2-bromo-4-(but-3-ynyl)phenoxy)(tert-butyl)dimethylsilane (S3)
A literature procedure3 was adapted. A well-stirred solution of alcohol S2 (50 mg, 0.14
mmol) in 2 mL of dry CH2Cl2 was treated with Et3SiH (45 µL, 0.28 mmol), and the
mixture was cooled at 0 ºC before BF3·OEt2 (35.3 µL, 0.28 mmol) was added. The
mixture was stirred at the same temperature for about 1 hr before diluting with 30 mL of
CH2Cl2. The mixture was washed with NaHCO3 saturated solution (20 mL), and the
resulting aqueous layer was back-extracted with CH2Cl2 (1 × 20 mL). Combined organic
layer was dried over Na2SO4, filtered, and concentrated in rotavapor. The title compound
(35.1 mg, 73% yield) was obtained after FCC using 195:5 hexanes/ethyl acetate.
IR (neat) 3308, 2953, 2930, 2859, 1602, 1495, 1289, 1257, 1046, 920, 840, 781, cm-1
1
6.79 (d, J = 8.2 Hz, 1 H), 2.74 (t, J = 7.5 Hz, 2 H), 2.43 (td, J = 7.5, 2.6 Hz, 2 H), 1.98 (t,
J = 2.6 Hz, 1 H), 1.03 (s, 9 H), 0.23 (s, 6 H)
13
120.1, 69.3 CH2 33.7, 20.7; CH3 25.8 (3), -4.0 (2)
OTBS OTBS
Br Br
LHMDS; MeI
THF, -78 ºC! rt
H Me
S4
(2-bromo-4-(pent-3-ynyl)phenoxy)(tert-butyl)dimethylsilane (S4)
A well-stirred solution of alkyne S3 (72.5 mg, 0.21 mmol) in 2 mL of dry THF was
added slowly to a freshly prepared solution of LHMDS (0.25 mmol) in 2 mL of dry THF,
S6
held at –78 ºC. The mixture was stirred for about 30 min at the same temperature before
MeI (39.9 µL, 0.64 mmol) was added. Stirring was continued allowing the reaction
mixture to gradually reach room temperature, and monitoring by GC analysis. After 4
hrs, the mixture was quenched with 20 mL of NH4Cl saturated solution, and extracted
with Et2O (3 × 20 mL). Combined organic layer was washed with 20 mL of Na2S2O3
saturated solution, dried over MgSO4, filtered, and concentrated in rotavapor. The title
compound (68.2 mg, 90% yield) was obtained after FCC using 195:5 hexanes/ethyl
acetate. On some runs, the compound was obtained as a mixture containing ~ 15% of
starting material. Resubmission of this mixture to the reaction conditions afforded pure
material in 64–80% yield.
IR (neat) 2953, 2930, 2858, 1602, 1494, 1288, 1257, 1046, 921, 840.2, 781.8 cm-1
1
6.80 (d, J = 8.2 Hz, 1 H), 2.70 (t, J = 7.5 Hz, 2 H), 2.33–2.42 (m, 2 H), 1.78 (t, J = 2.5
Hz, 3 H), 1.05 (s, 9 H), 0.25 (s, 6 H)
13
C NMR (75 MHz, CDCl3, DEPT) δ C 151.0, 135.3, 115.1, 78.4, 69.3, 18.5; CH 133.5,
128.5, 120.1 CH2 34.4, 21.1; CH3 25.8 (3), 3.6, -4.0 (2)
OTBS OH
Br Br
LiOH, DMF, rt
Me Me
S5
2-bromo-4-(pent-3-ynyl)phenol (S5)
A literature procedure4 was implemented. A well-stirred solution of TBS ether S4 (68

mg, 0.19 mmol) in 2 mL of wet DMF was treated with LiOH·H2O (24.2 mg, 0.57 mmol).
The reaction mixture was stirred at room temperature for 1.5 hrs before 30 mL of ethyl
acetate was added. The mixture was washed with brine (2 × 20 mL), dried over Na2SO4,
filtered, and concentrated in rotavapor. The title compound (38.8 mg, 84% yield) was
obtained after FCC using 9:1 hexanes/ethyl acetate.
IR (neat) 3504, 2918, 1607, 1579, 1495, 1416, 1331, 1286, 1254, 1183, 1040, 820 cm-1
1
6.93 (d, J = 8.4 Hz, 1 H), 5.42 (s, 1 H), 2.69 (t, J = 7.5 Hz, 2 H), 2.31–2.42 (m, 2 H), 1.77
(t, J = 2.5 Hz, 3 H)
13
115.9 CH2 34.3, 21.2; CH3 3.6
S7
OH O
Br Br
BAIB, NaHCO3
Me MeOH, 0 ºC Me
MeO
2-bromo-4-methoxy-4-(pent-3-ynyl)cyclohexa-2,5-dienone (2d)
A well-stirred solution of phenol S5 (65 mg, 0.27 mmol) in 2.5 mL of anhydrous

methanol was treated with NaHCO3 (114.1 mg, 1.35 mmol). The mixture was cooled to 0
ºC before BAIB (105.0 mg, 0.32 mmol) was added in small portions. Stirring was
continued for about 30 min. and the mixture was concentrated in rotavapor. The title
compound was obtained after purification by FCC using 9:1 hexanes (41 mg, 56% yield).
IR (neat) 2934, 1674, 1603, 1451, 1333, 1086, 828.1 cm-1

1
6.47 (d, J = 10.1 Hz, 1 H), 3.21 (s, 3 H), 2.12–2.25 (m, 2 H), 1.84–2.03 (m, 2 H), 1.74 (t,
J = 2.5 Hz, 3 H)
13
C NMR (75 MHz, CDCl3, DEPT) δ C 178.2, 126.2, 78.0, (2) 77.6; CH 151.4, 150.7,
130.14 CH2 39.0, 13.6; CH3 53.5, 3.6
OTBS OTB S
Br PhI, PdCl2(PPh3) 2 Br
CuI
H Et3N, rt
S6
(2-bromo-4-(4-phenylbut-3-ynyl)phenoxy)(tert-butyl)dimethylsilane (S6)
A literature procedure5 was adapted. A mixture of alkyne S3 (35.1 mg, 0.1 mmol), and
iodobenzene (11.5 µL, 0.1 mmol) was dissolved in 1 mL of dry Et3N and added to a well
stirred suspension of PdCl2(PPh3)2 (0.72 mg, 0.001 mmol) and CuI (0.1 mg, 0.0005
mmol) in 1 mL of dry Et3N. The mixture was stirred under N2 for 18 hrs and then diluted
with 30 mL of Et2O and washed with 1 N HCl solution (2 ×20 mL). The organic layer
was dried over MgSO4, filtered and concentrated in rotavapor. The title compound (41.3
mg, 96% yield) was obtained after purification by FCC using 195:5 hexanes/ethyl
acetate.
IR (neat) 3031, 2995, 2930, 2859, 1601, 1494, 1291, 1258, 1046, 921 cm-1
1
H NMR (300 MHz, CDCl3) δ 7.45 (d, J = 2.1 Hz, 1 H), 7.33–7.40 (m, 2 H), 7.24–7.30
(m, 3 H), 7.05 (dd, J = 8.3, 2.1 Hz, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 2.81 (t, J = 7.4 Hz, 2
H), 2.64 (t, J = 7.4 Hz, 2 H) 1.09 (s, 9 H), 0.24 (s, 6 H)
S8
13
C NMR (75 MHz, CDCl3, DEPT) δ C 151.1, 135.0, 123.8, 115.2, 89.3, 81.8, 18.5; CH
133.5, 131.7 (2), 128.5, 128.3 (2), 127.8, 120.1; CH2 34.0, 21.9; CH3 25.9 (3), –4.0 (2)
OTBS OH
Br Br
LiOH, DMF, rt
S7
2-bromo-4-(4-phenylbut-3-ynyl)phenol (S7)
A literature procedure4 was implemented. A solution of TBS ether S6 (39.6 mg, 0.095
mmol) in 1 mL of wet DMF was treated with LiOH·H2O (12 mg, 0.28 mmol). The
mixture was stirred for 18 hrs at room temperature, and then diluted with ethyl acetate
(30 mL). The mixture was washed with water (2 × 20 mL) and brine (2 × 20 mL), dried
over Na2SO4, filtered and concentrated in rotavapor. The title compound (20.9 mg, 73%
yield) was obtained after purification by FCC using 5:1 hexanes/ethyl acetate.
IR (neat) 3508, 2926, 1604, 1494, 1182, 1040, 755 cm-1

1
H NMR (300 MHz, CDCl3) δ 7.34–7.41 (m, 3 H), 7.25–7.31 (m, 3 H), 7.13 (dd, J = 8.2,
2.0 Hz, 1 H), 6.96 (d, J = 8.2 Hz, 1 H), 5.41 (s, 1 H), 2.83 (t, J = 7.2 Hz, 2 H), 2.65 (t, J =
7.4 Hz, 2 H)
13
C NMR (75 MHz, CDCl3, DEPT) δ C 150.9, 134.5, 123.8, 110.10, 89.1, 81.9; CH
132.0, 131.7 (2), 129.6, 128.4 (2), 127.9, 116.0; CH2 34.0, 21.9
OH O
Br BAIB, NaHCO3 Br
MeOH, 0ºC
MeO
2-bromo-4-methoxy-4-(4-phenylbut-3-ynyl)cyclohexa-2,5-dienone (2c)
A solution of phenol S7 (20 mg, 0.066 mmol) in 1 mL of anhydrous MeOH was treated
with NaHCO3 (27.8 mg, 0.33 mmol), followed by BAIB (25.6 mg, 0.079 mmol). The
mixture was stirred for 30 min. at the same temperature, and then concentrated in
rotavapor. Residue was purified by FCC using 9:1 hexanes/ethyl acetate to give 10.7 mg
of the title compound in 48% yield.
IR (neat) 3052, 2930, 2827, 1671, 1599, 1490, 1441, 1330, 1092 cm-1
1
H NMR (300 MHz, CDCl3) δ 7.35–7.39 (m, 2 H), 7.33 (d, J = 3.0 Hz, 1 H), 7.25–7.30
(m, 3 H), 6.85 (dd, J = 10.2, 3.0 Hz, 1 H), 6.51 (d, J = 10.2 Hz, 1 H), 3.25 (s, 3 H), 2.40–
2.59 (m, 2 H) 2.00–2.17 (m, 2 H)
S9
13
150.7, 131.7 (2), 130.2, 128.4 (2), 128.0; CH2 38.8, 14.3; CH3 53.6
OH OTBS
TBSCl, DMAP,
Imidazole
OMe OMe
CH2Cl2, rt
O H O H
S8
4-(tert-butyldimethylsilyloxy)-2-methoxybenzaldehyde (S8)
A solution of 2-methoxy-4-hydroxybenzaldehyde (500 mg, 3.28 mmol) in 30 mL of dry

CH2Cl2 was treated with imidazole (894 mg, 13.1 mmol) DMAP (20 mg, 0.16 mmol) and
TBSCl (594.3 mg, 3.94 mmol). The mixture was stirred at room temperature for 12 hrs
and then diluted with 30 mL of water. The phases were separated, and the organic layer
was washed with water (2 × 20 mL) and brine (2 × 20 mL), dried over Na2SO4, filtered
and concentrated. The title compound was obtained (583.2 mg, 66% yield) after FCC
purification using 95:5 hexanes/ethyl acetate.
IR (neat) 2957, 2934, 2886, 2859, 1682, 1600, 1503, 1284, 1208, 1168, 1105, 979, 859,
809, 785 cm-1
1
H NMR (300 MHz, CDCl3) δ 10.16 (s, 1 H), 7.59 (d, J = 8.4 Hz, 1 H), 6.32 (dd, J = 8.4,
1.9 Hz, 1 H), 6.28 (d, J = 1.9 Hz, 1 H), 3.72 (s, 3 H), 0.86 (s, 9 H), 0.12 (s, 6 H)
13
C NMR (75 MHz, CDCl3, DEPT) δ C 163.4, 162.7, 119.2, 18.0; CH 187.7, 129.9,
112.3, 103.1; CH3 55.3, 25.3 (3), –4.5 (2)
H
OTBS Br OTBS
Znº, TiCl4
MeO THF, 0 ºC MeO H
O H HO
S9
1-(4-(tert-butyldimethylsilyloxy)-2-methoxyphenyl)but-3-yn-1-ol (S9)
A well-stirred suspension of activated zinc dust (216.4 mg, 3.31 mmol) in 10 mL of dry
THF was cooled to 0 ºC and treated with propargyl bromide (0.49 mL of a 80% wt
solution in toluene, 3.31 mmol), followed by TiCl4 solution (55 µL of a 1 M solution in
CH2Cl2, 0.055 mmol). The mixture was stirred for about 5 min. before a solution of
aldehyde S8 (294.0 mg, 1.1 mmol) in 7 mL of dry THF was added. The reaction mixture
was stirred at the same temperature for 2 hr and then diluted with 30 mL of Et2O, and
washed with 30 mL of NH4Cl saturated solution and 30 mL of brine. Aqueous layer was
S10
back-extracted with Et2O (2 × 30 mL). Combined organic layer was dried over MgSO4,
filtered, and concentrated in rotavapor. Product was purified by FCC using 9:1
hexanes/ethyl acetate to obtain 299.7 mg (88% yield)
IR (neat) 3443, 3310, 2955, 2933, 2859, 1609, 1585, 1504, 1464, 1293, 1257, 1202,
1161, 980, 843.6, 781.7 cm-1
1
6.37 (d, J = 8.2 Hz, 1 H), 4.99 (dt, J = 7.5, 5.6 Hz, 1 H), 3.80 (s, 3 H), 2.80 (d, J = 5.6 Hz,
1 H ), 2.71 (ddd, J = 16.7, 5.1, 2.6 Hz, 1 H), 2.61 (ddd, J = 16.7, 7.6, 2.6 Hz, 1 H), 2.03
(t, J = 2.6 Hz, 1 H), 0.98 (s, 9 H), 0.20 (s, 6 H)
13
103.5, 81.7, 68.9; CH2 27.6; CH3 55.4, 25.8 (3), -4.2 (2)
OTBS O TB S
Et3SiH, BF3•OEt2
MeO H CH2Cl2, 0 ºC MeO H
HO
S 10
(4-(but-3-ynyl)-3-methoxyphenoxy)(tert-butyl)dimethylsilane (S10)
A literature procedure3 was adapted. A well-stirred solution of alcohol S9 (299.7 mg,

0.97 mmol) in 10 mL of dry CH2Cl2 was treated with Et3SiH (0.46 mL, 2.93 mmol), and
the mixture was cooled at 0ºC before BF3·OEt2 (0.36 mL, 2.93 mmol) was added. The
mixture was stirred at the same temperature for about 2 hr before quenching with
NaHCO3 saturated solution (20 mL), CH2Cl2 (30 mL) was added, and the layers were
separated. Organic layer was dried over Na2SO4, filtered, and concentrated in rotavapor.
The title compound (142.6 mg, 50% yield) was obtained after FCC using 99:1
hexanes/ethyl acetate.
IR (neat) 3307, 2954, 2934, 1608, 1586, 1504, 1454, 1412, 1293, 1258, 1162, 1114,
1039, 844, 781, cm-1
1
H NMR (300 MHz, CDCl3) δ 6.99 (dd, J = 6.4, 2.2 Hz, 1 H), 6.32–6.39 (m, 2 H), 3.77
(s, 3 H), 2.78 (t, J = 7.8 Hz, 2 H), 2.42 (td, J = 7.8, 2.5 Hz, 2 H), 1.95 (t, J = 2.5 Hz, 1 H),
0.99 (s, 9 H), 0.21 (s, 6 H)
13
103.4, 84.8 CH2 29.5, 19.2; CH3 25.8 (3), -4.2 (2)
OTBS OTBS
LHMDS; MeI
THF, -78 ºC! rt
MeO H MeO Me
S11
S11
tert-butyl(3-methoxy-4-(pent-3-ynyl)phenoxy)dimethylsilane (S11)
A well-stirred solution of alkyne S10 (112 mg, 0.38 mmol) in 4 mL of dry THF was
added slowly to a freshly prepared solution of LHMDS (1.38 mmol) in 2 mL of dry THF,
held at –78 ºC. The mixture was stirred for about 45 min at the same temperature before
MeI (0.12 mL, 1.92 mmol) was added. Stirring was continued allowing the reaction
mixture to gradually reach room temperature. After 4hrs, GC monitoring showed ~85%
conversuion, the mixture was cooled back to –78 ºC and treated with an equal amount of
LHMDS, stirred for 30 min and more MeI (0.12 mL) was added. Stirring continued for 1
hr at room temperature, before quenching with 20 mL of NH4Cl saturated solution, and
extracting with Et2O (3 × 20 mL). Combined organic layer was washed with 20 mL of
Na2S2O3 saturated solution, dried over MgSO4, filtered, and concentrated in rotavapor.
The title compound (94.2 mg, 80% yield) was obtained after FCC using 195:5
hexanes/ethyl acetate.
IR (neat) 2932, 2859, 2359, 1608, 1503, 1463, 1292, 1257, 1202, 1161, 1113, 978, 842,
781 cm-1
1
H NMR (300 MHz, CDCl3) δ 6.98 (d, J = 8.6 Hz, 1 H), 6.34–6.39 (m, 2 H), 3.77 (s, 3
H) 2.69–2.77 (m, 2 H), 2.30–2.40 (m, 2 H), 1.78 (t, J = 2.5 Hz, 3 H), 1.00 (s, 9 H), 0.21
(s, 6 H)
13
111.3, 103.4 CH2 30.0, 19.6; CH3 55.3, 25.9 (3), 3.6, -4.2 (2)
OTBS OH
LiOH, DMF, rt
MeO Me MeO Me
S12
3-methoxy-4-(pent-3-ynyl)phenol (S12)
A literature procedure4 was implemented. A well-stirred solution of TBS ether S11 (92
mg, 0.3 mmol) in 3 mL of wet DMF was treated with LiOH·H2O (38.0 mg, 0.9 mmol).
The reaction mixture was stirred at room temperature for 12 hrs before diluting with 30
mL of ethyl acetate. The mixture was washed with brine (2 × 20 mL), dried over Na2SO4,
filtered, and concentrated in rotavapor. The title compound (60.3 mg, >99% yield) was
obtained after FCC using 5:1 hexanes/ethyl acetate.
IR (neat) 3372, 2921, 1659, 1614, 1599, 1510, 1469, 1434, 1287, 1197, 1156, 1113,
1037, 954, 833.6 cm-1
1
H NMR (300 MHz, CDCl3) δ 6.97 (d, J = 8.3 Hz, 1 H), 6.32–6.42 (m, 2 H), 3.73 (s, 3
H), 2.71 (t, J = 7.7 Hz, 2 H), 2.28–2.39 (m, 2 H), 1.77 (t, J = 2.3 Hz, 3 H) 0.92 (d, J = 4.8
Hz, 1 H)
S12
13
99.0 CH2 29.8, 19.5; CH3 55.3, 3.6
OH O
PIFA, NaHCO3
MeO Me MeOH, 0 ºC MeO Me

MeO
3,4-dimethoxy-4-(pent-3-ynyl)cyclohexa-2,5-dienone (2h)
A well-stirred solution of phenol S12 (38 mg, 0.2 mmol) in 2.5 mL of anhydrous MeOH
was treated with NaHCO3 (84.01 mg, 1.0 mmol) and cooled to 0 ºC. PIFA (94.6 mg, 0.22
mmol) was added and the reaction mixture was stirred at the same temperature for 10
min., after which it was quickly concentrated onto ~50 mg of basic alumina. FCC of the
adsorbed mixture (3:1 hexanes/ethyl acetate) using basic alumina as stationary phase
afforded 18.4 mg (42% yield) of the title compound.
IR (neat) 2936, 1663, 1599, 1449, 1367, 1224, 1093, 857 cm-1
1
H NMR (300 MHz, C6D6) δ 6.18 (dd, J = 10.1, 1.7 Hz, 1 H), 5.83 (d, J = 10.1 Hz, 1 H),
5.48 (d, J = 1.7 Hz, 1 H), 2.85 (s, 3 H), 2.79 (s, 3 H), 2.20–2.37 (m, 1 H), 1.83–2.11 (m, 3
H), 1.48 (t, J = 2.3 Hz, 3 H)
13
C NMR (75 MHz, C6D6, DEPT) δ C 185.9, 171.5, 78.3, 76.5, 76.2; CH 144.9, 131.8,
105.7 CH2 37.9, 13.7; CH3 54.8, 51.9, 3.2
OH OH
Br
TBA-Br3
Me
CH2Cl2-MeOH Me
rt
Me Me
S13
2-bromo-4,5-dimethylphenol (S13)
A literature procedure6 was implemented. A well-stirred solution of 3,4-dimethylphenol

(500 mg, 4.09 mmol) in CH2Cl2 ( 30 mL) and MeOH (20 mL) was treated with TBA-Br3
(1.97 g, 4.09 mmol) at room temperature. The mixture was stirred at room temperature
for 40 min. and then concentrated in rotavapor. The residue was taken up in 40 mL of
water and the mixture extracted with Et2O (3 × 40 mL). Organic layer was dried over
MgSO4, filtered and concentrated in rotavapor. FCC purification using 9:1 hexane/ethyl
acetate afforded the title compound (730 mg, 88% yield) contaminated with ~ 10% of
regioisomeric product, which can be removed by recrystallization from MeOH-water.
IR (neat) 3318, 3249, 1607, 1500, 1405, 1271, 1189, 1147, 1010, 979, 865.4, 842 cm-1
S13
1
H NMR (300 MHz, CDCl3) δ 7.19 (s, 1 H), 6.81 (s, 1 H), 5.24 (s, 1 H), 2.18 (s, 3 H),
2.16 (s, 3 H)
13
C NMR (75 MHz, CDCl3, DEPT) δ C 150.1, 138.0, 130.4, 106.6; CH 132.3, 117.2;
CH3 19.7, 18.8
OH Me O
HO
Br Br
Me
PIFA,
Me 0 ºC Me
Me O
Me
2-bromo-4-(but-2-ynyloxy)-4,5-dimethylcyclohexa-2,5-dienone (2g)
A mixture of phenol S13 (201.1 mg, 1.0 mmol) and 1 mL of 2-butyn-1-ol was cooled to 0
ºC and treated with PIFA (516.0 mg, 1.2 mmol). The mixture was stirred at the same
temperature for 20 min. and then concentrated under high vacuum. The residue was
loaded into a FCC and purified using 9:1 hexanes/ethyl acetate to give 201.5 mg (74%
yield) of the title compound.
IR (neat) 3042, 2990, 2912, 2360, 2338, 1668, 1601, 1431, 1379, 1331, 1223, 1079, 1031
cm -1
1
H NMR (300 MHz, CDCl3) δ 7.31 (s, 1 H), 6.30 (q, J = 1.5 Hz, 1 Hz), 3.88 (dq, J =
14.7, 2.3 Hz, 1 H), 3.81 (dq, J = 14.7, 2.3 Hz, 1 H), 2.03, (d, J = 1.5 Hz, 3 H), 1.86 (t, J =
2.3 Hz, 3 H), 1.48 (s, 3 H)
13
127.4, CH2 54.3; CH3 25.4, 17.8, 3.7
HRMS (ESI) 290.9997 calc for C12H13BrNaO2 found 290.9991
General Procedure for Pd-Catalyzed Cyclization Reactions. A mixture of the

cyclohexadienone (1 equiv.), Pd(OAc)2 (0.05 equiv.) and bipy (0.1 equiv.) was placed
under N2 atmosphere and suspended in dry AcOH (0.1 M). The mixture was then heated
to 60 ºC or 80 ºC and monitored by TLC. (2–22 hrs). After the reaction was complete, the
solvent was removed under vacuum and the residue was loaded directly into a silica
column for flash chromatography. Alternatively, reactions run on >1 mmol scale were
diluted with EtOAc and washed with H2O (1×), sat. aq. NaHCO3, (3×) and brine. The
organic layer dried over Na2SO4, filtered, and concentrated in vacuo before purification.
Cyclization Products
O O
Me Pd(OAc)2
bipy H Me
AcOH, 80 ºC
Me O Me OAc
O
(Z)-1-(7a-methyl-5-oxo-4,5-dihydrobenzofuran-3(2H,3aH,7aH)-ylidene)ethyl acetate
(3a)
S14
Obtained in 80% yield using the general procedure. Purification of the product was
performed by FCC using 5:1 hexanes/ethyl acetate.
Relative stereochemistry was assigned based on the following nOe interactions (GOESY,
500 Mhz, CDCl3):
O
3.91% 2.58%
H Me
Me OAc
O
IR (neat) 2973, 2927, 2853, 2360, 2341, 1755, 1691, 1374, 1212, 1012 cm-1
1
H NMR (300 MHz, CDCl3) δ 6.54 (d, J = 10.2 Hz, 1 H), 6.01 (d, J = 10.2 Hz, 1 H),
4.27-4.35 (m, 1 H), 4.22 (dp, J = 13.3, 2.1 Hz, 1 H), 3.05 (t, J = 5.9 Hz, 1 H), 2.76 (dd, J
= 16.3, 6.5 Hz, 1 H), 2.58 (dd, J = 16.3, 5.6 Hz, 1 H), 2.09 (s, 3 H), 1.91 (q, J = 1.8 Hz, 3
H), 1.45 (s, 3 H).
13
C NMR (75 MHz, CDCl3, DEPT) δ C 197.4, 168.4, 139.0, 127.9, 80.2; CH 149.8,
129.8, 45.4; CH2 38.1; CH3 23.8, 20.8, 17.2.
O O O
Me
Pd(OAc) 2
bipy H Me + Me Me
Me AcOH, 60 ºC Me
Me O Me O Ac Me OAc
O O
(Z)-1-(7,7a-dimethyl-5-oxo-4,5-dihydrobenzofuran-3(2H,3aH,7aH)-ylidene)ethyl
acetate (3fa) and (Z)-1-(3a,7a-dimethyl-5-oxo-4,5-dihydrobenzofuran-
3(2H,3aH,7aH)-ylidene)ethyl acetate (3fb)
Using the general procedure, the title compounds was obtained in 90% combined yield.
Analysis of the crude mixture by 1H NMR showed a dr of 1.25:1 Samples suitable for
characterization of each of the diastereomers were obtained by iterative FCC purification
(1:1 hexanes/ethyl acetate, anisaldehyde stain).
Data for major compound (3fa)

IR (neat) 2979, 2918, 2850, 1753, , 1676, 1438, 1374, 1209, 1151, 1014 cm-1
1
H NMR (300 MHz, CDCl3) δ 5.89 (bs, 1 H), 4.25 (d, J = 13.1 Hz, 1 H), 4.04 (dp, J =
13.1, 2.2 Hz, 1 H), 3.05 (m, 1 H), 2.82 (dd, J = 16.6, 4.8 Hz, 1 H), 2.59 (dd, J = 16.6, 5.5
Hz, 1 H), 2.08 (s, 3 H), 1.94 (d, J = 1.0 Hz, 3 H), 1.90 (q, J = 2.2 Hz, 3 H) 1.49 (s, 3 H)
13
128.3, 46.2; CH2 67.5, 37.6; CH3 22.2, 20.7, 18.2, 17.0
Data for minor compound (3fb)

IR (neat) 2975, 2934, 2858, 1754, 1694, 1443, 1373, 1224, 1205, 1166, 1029 cm-1
S15
1
H NMR (300 MHz, CDCl3) δ 6.48 (d, J = 10.2 Hz, 1 H), 5.97 (d, J = 10.2 Hz, 1 H), 4.27
(dq, J = 13.5, 1.9 Hz, 1 H), 4.05 (dq, J = 13.5, 1.9 Hz, 1 H), 2.92 (d, J = 16.3 Hz, 1 H),
2.43 (d, J = 16.3 Hz, 1 H), 2.05 (s, 3 H), 1.90 (t, J = 1.9 Hz, 3 H), 1.34 (s, 3 H), 1.20 (s, 3
H),
13
129.9; CH2 67.6, 44.8; CH3 20.0, 20.8, 18.2, 16.5
O O O O
Me Me Pd(OAc) 2 Me Me Me
bipy Me + Me
H H +
Me
AcOH, 80 ºC
Me O Me O Ac Me Me O Ac
O O O
O Ac
6.15 : 1.25 : 1
(Z)-1-(6,7a-dimethyl-5-oxo-4,5-dihydrobenzofuran-3(2H,3aH,7aH)-ylidene)ethyl
acetate (3e)
Using the general procedure, the major product was obtained in 55% yield by FCC
purification (9:1 hexanes/acetone).
Data for major compound (3e):
IR (neat) 2975, 2929, 2858, 1755, 1684, 1440, 1370, 1208, 1147, 1014 cm-1
1
H NMR (300 MHz, CDCl3) δ 6.30 (bs, 1 H), 4.17–4.32 (m, 2 H), 3.00 (t, J = 6.4 Hz, 1
H), 2.72 (dd, J = 16.1, 7.1 Hz, 1 H), 2.55 (dd, J = 16.1, 5.6 Hz, 1 H), 2.07 (s, 3 H), 1.89
(bs, 3 H), 1.76 (bs, 3 H), 1.40 (s, 3 H).
13
144.7, 45.6; CH2 67.5, 38.5; CH3 24.2, 20.8, 17.2, 15.77
O O
Br Me Pd(OAc)2 Br
bipy H Me
AcOH, 80 ºC
Me O Me OAc
O
(Z)-1-(6-bromo-7a-methyl-5-oxo-4,5-dihydrobenzofuran-3(2H,3aH,7aH)-
ylidene)ethyl acetate (3b)
Using the general procedure, the title compound was obtained in 62% yield by FCC
purification (5:1 hexanes/ethyl acetate).
On scaling, 718.5 mg, (2.81 mmol) of the alkyne in 12 ml of acetic acid were treated with
31.6 mg of Pd(OAc)2, and 43.9 mg of bipy. The mixture was heated at 80 ºC for 8 hrs and
then cooled to room temperature. Ethyl acetate (100 mL) was added, and the mixture was
washed with water (2 × 30 mL), NaHCO3, (2 × 30 mL), and brine (2 × 30 mL), dried
S16
over Na2SO4, filtered and concentrated in rotavapor. Residual product was purified by
FCC (5:1 hexanes/ethyl acetate) to give 398.4 mg of the title compound (45% yield)
IR (neat) 2973, 2928, 2854, 1754, 1702, 1373, 1208, 1148, 1012 cm-1
1
H NMR (300 MHz, CDCl3) δ 6.99 (s, 1 H), 4.32 (bd, J = 13.6 Hz, 1 H), 4.25 (dp, J =
13.6, 2.1 Hz, 1 H), 3.10 (t, J = 5.6 Hz, 1 H), 2.98 (dd, J = 16.2, 6.3 Hz, 1 H), 2.73 (dd, J
= 16.2, 5.3 Hz, 1 H), 2.10 (s, 3 H), 1.91 (q, J = 1.6 Hz, 3 H), 1.48 (s, 3 H).
13
C NMR (75 MHz, CDCl3, DEPT) δ C 189.4, 168.4, 139.6, 127.0, 124.8 82.7; CH
150.2, 45.5; CH2 68.0, 38.1; CH3 23.6, 20.8, 17.3.
HRMS (ESI+) calc for C13H15BrNaO4 337.0051 found 337.0046
O O O
Br Me Pd(OAc) 2 Br Br
bipy H Me Me
+
AcOH, 80 ºC
MeO MeO O Ac MeO OAc
(E)-1-(5-bromo-3a-methoxy-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-inden-1-ylidene)ethyl
acetate (3d)
Title obtained as a 5.25:1 mixture with non-cyclized product in 61% combined yield
using the general procedure and FCC purification (5:1 hexanes/ethyl acetate).
Data for major compound (3d):
IR (neat) 2934, 2358, 1750, 1697, 1604, 1372, 1206, 1144, 1080 cm-1
1
H NMR (300 MHz, CDCl3) δ 7.31 (s, 1 H), 3.37 (dd, J = 12.8, 5.9 Hz, 1 H), 3.27 (s, 3
H), 2.90 (dd, J = 16.5, 6.0 Hz, 1 H), 2.45 (dd, J = 16.5, 12.8 Hz, 1 H) , 2.12 (s, 3 H),
1.90–2.25 (m, 4 H), 1.88 (bs, 3 H)
13
151.3, 44.9; CH2 41.0, 34.4, 26.8; CH3 51.6, 20.9, 17.2
O O
Br Ph Pd(OAc)2 Br
bipy Ph
H + Other compounds
AcOH, 80 ºC
MeO MeO OAc
2.4 : 1
(E)-(5-bromo-3a-methoxy-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-inden-1-
ylidene)(phenyl)methyl acetate (3c)
Title compound obtained as a 2.4:1 mixture in 67% combined yield, not separated from
minor products. FCC purification (5:1 hexanes/ethyl acetate).
Data for major compound (3c):
IR (neat) 3052, 2930, 2834, 1751, 1695, 1605, 1450, 1212, 1056, 901 cm-1
S17
1
H NMR (300 MHz, CDCl3) δ 7.30–7.38 (m, 5 H), 7.29 (s, 1 H), 3.54 (dd, J = 11.8, 6.0
Hz, 1 H), 3.24 (s, 3 H), 2.59–2.77 (m, 3 H), 2.41 (dd, J = 16.8, 11.8 Hz, 1 H), 2.13 (s, 3
H), 1.99–2.18 (m, 2 H)
13
C NMR (75 MHz, CDCl3, DEPT) δ C 189.3, 168.6, 142.5, 135.3, 131.9, 125.3, 86.3;
CH 151.4, 129.0, 128.8, 128.0, 44.8; CH2 40.3, 34.5, 27.6; CH3 51.8, 20.9
O O
Me Pd(OAc)2
bipy H Me
MeO AcOH, 80 ºC MeO
MeO MeO OAc
(E)-1-(3a,4-dimethoxy-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-inden-1-ylidene)ethyl
acetate (3h)
Using the general procedure, the title compound was obtained in 49% yield by FCC
purification (9:1 hexanes/ethyl acetate).
IR (neat) 2932, 1749, 1658, 1605, 1364, 1221 cm-1

1
H NMR (300 MHz, CDCl3) δ 5.47 (s, 1 H), 3.77 (s, 3 H), 3.32 (dd, J = 12.6, 6.2 Hz, 1
H), 3.17 (s, 3 H), 2.66 (dd, J = 16.5, 6.2 Hz, 1 H), 2.38–2.60 (m, 2 H), 2.31 (dd J = 16.5,
12.8 Hz, 1 H), 2.11 (s, 3 H), 2.00–2.21 (m, 2 H), 1.89 (bs, 3 H).
13
104.6, 42.8; CH2 40.9, 34.7, 26.3; CH3 56.4, 51.5, 20.9, 17.1
O O
Br Pd(OAc)2 Br
Me bipy
Me Me
Me AcOH, 80 ºC
Me O Me OAc
O
(Z)-1-(6-bromo-3a,7a-dimethyl-5-oxo-4,5-dihydrobenzofuran-3(2H,3aH,7aH)-
ylidene)ethyl acetate (3g)
Using the general procedure, the title compound was obtained as a single diastereomer in
55% yield after FCC purification (5:1 hexanes/ethyl acetate).
IR (neat) 2976, 2930, 2854, 1754, 1701, 1668, 1607, 1372, 1214, 1169, 1029 cm -1
1
H NMR (300 MHz, CDCl3) δ 6.94 (s, 1 H), 4.30 (dq, J = 13.6, 1.8 Hz, 1 Hz), 4.10 (dq, J
= 13.6, 1.8 Hz, 1 H), 3.15 (d, J = 16.4 Hz, 1 H), 2.53, (d, J = 16.4 Hz, 1 H), 2.06 (s, 3 H),
1.90 (t, J = 1.8 Hz, 3 H), 1.36 (s, 3 H), 1.20 (s, 3 H)
13
C NMR (75 MHz, CDCl3, DEPT) δ C 189.5, 168.2, 138.9, 130.5, 124.0, 86.3, 47.4; CH
153.2; CH2 67.8, 44.4; CH3 21.8, 20.8, 18.1, 16.6
HRMS (ESI) 351.0208 calc for C14H17BrNaO4 found 351.0202
S18
O OH
Br NaBH4, CeCl3 Br
Me
MeOH Me
H H
0 ºC! rt
Me OAc Me OAc
O O
S14
(Z)-1-(6-bromo-5-hydroxy-7a-methyl-4,5-dihydrobenzofuran-3(2H,3aH,7aH)-
ylidene)ethyl acetate (S14)
A literature procedure7 was adapted. A well-stirred solution of enone (3b), (50 mg, 0.15
mmol) in 1.5 mL of anhydrous methanol was treated with CeCl3 (39.1 mg, 0.15 mmol)
and cooled to 0 ºC. NaBH4 (6.0 mg, 0.15 mmol) was added in one portion and the cooling
bath was removed. The mixture was stirred at room temperature for about 15 minutes
before quenching with water (10 mL) and poured into a separatory funnel containing 30
mL of CH2Cl2. After shaking, the phases were separated, and the organic layer was dried
over Na2SO4, filtered, and concentrated under reduced pressure to obtain 48.7 mg the title
compound as a single diastereomer without need for chromatographic purification (97%
yield). Relative configuration of the newly formed stereogenic center was assigned based
on the following nOe interactions (GOESY, 500 MHz, CDCl3):
OH 1.49%
H
Br 2.92%
H Me
Me OAc
O
4.07%
IR (neat) 3474, 2967, 2926, 2857, 1747, 1642, 1438, 1374, 1209, 1149, 1011 cm-1
1
H NMR (300 MHz, CDCl3) δ 5.90 (s, 1 H), 4.27 (d, J = 13.2 Hz, 1 H), 4.11 (m, 1 H),
4.05 (dt, J = 13.2, 2.2 Hz, 1 H), 3.27 (d, J = 10.2 Hz, 1 H), 2.70 (bs, 1 H), 2.40 (ddd, J =
14.6, 5.7, 4.0 Hz, 1 H), 2.10 (s, 3 H), 2.04 (dt, J = 14.6, 4.6 Hz, 1 H), 1.94 (q, J = 1.8
Hz, 3 H), 1.33 (s, 3 H).
13
41.9; CH2 66.9, 31.6; CH3 24.1, 20.6, 17.7
HRMS (ESI+) 339.0208 calc for C13H17NaBrO4 found 339.0202
OH OH
Br K2CO3 Br
MeOH-H2O
H Me H Me
rt
Me OAc Me O
O O
1-(6-bromo-5-hydroxy-7a-methyl-2,3,3a,4,5,7a-hexahydrobenzofuran-3-yl)ethanone
(7)
S19
A well-stirred solution of enol acetate (S14), (48 mg, 0.15 mmol) in 1.5 mL of a 1.5:1
mixture of methanol-water was treated with K2CO3 (1.93 mg, 0.015 mmol). The mixture
was stirred at room temperature for about 1 hr before quenching with 5 mL of NH4Cl
saturated solution and extracted with CH2Cl2 (3 × 20 mL). Organic layer was dried over
Na2SO4, filtered, and concentrated in rotavapor. 1H NMR analysis of the residue shows
formation of the title compound as a single diastereomer. Purification was performed by
FCC using 3:1 hexanes/ethyl acetate to give 35.9 mg of the title compound in 86% yield.
IR (neat) 3418, 2964, 2928, 2893, 1703, 1648, 1088 cm-1

1
H NMR (300 MHz, CDCl3) δ 5.97 (s, 1 H), 4.22 (d, J = 5.0 Hz, 1 H), 3.98 (t, J = 8.8 Hz,
1H), 3.89 (dd, J = 8.6, 6.0 Hz, 1 H), 3.81 (dt, J = 8.6, 6.0 Hz, 1 H), 2.51 (bs, 1 H), 2.38
(dt, J = 8.5, 3.8 Hz, 1 H), 2.25 (dq, J = 15.3, 1.9 Hz, 1 H), 2.20 (s, 3 H), 2.05 (dt, J =
15.3, 4.9 Hz, 1 H), 1.31 (s, 3 H).
13
C NMR (75 MHz, CDCl3, DEPT) δ C 208.0, 126.0, 83.2; CH 136.0, 68.7, 55.9, 42.3;
CH2 67.5, 30.0; CH3 30.0, 24.6
OH OH
PhB(OH)2 ,
Br (Cy3 P)2PdCl2 Ph
H Me Cs2CO3 H Me
Dioxane-H2O
Me O 100 ºC Me O
O O
1-(5-hydroxy-7a-methyl-6-phenyl-2,3,3a,4,5,7a-hexahydrobenzofuran-3-yl)ethanone
(8)
A literature procedure8 was adapted. A mixture of vinyl bromide (7), (32.8 mg, 0.12
mmol), Cs2CO3 (45 mg, 0.25 mmol) (Cy3P)2PdCl2, (94.7 mg, 0.0063 mmol) and
PhB(OH)2 (31.1 mg, 0.25 mmol) was dissolved in 3 mL of a 5:1 dioxane/water mixture.
The flask was adapted to a condenser, and the mixture heated at 100 ºC for 15 hrs. The
mixture was then allowed to cool to room temperature, diluted with water (10 mL) and
extracted with ethyl acetate (3 × 20 mL). Combined organic layer was dried over Na2SO4,
filtered and concentrated in rotavapor. Purification by FCC (2:1 hexanes/ethyl acetate)
afforded 27.9 mg of the title compound in 80% yield.
IR (neat) 3440, 2969, 2925, 1708, 1077 cm-1
1
H NMR (300 MHz, CDCl3) δ 7.28–7.51 (m, 5 H), 5.86 (s, 1 H), 4.79 (dd, J = 4.9, 2.3
Hz, 1H), 3.83–4.05 (m, 3 H), 2.42 (dt, J = 7.8, 3.8 Hz, 1 H), 2.27 (ddd, J = 15.2, 3.3, 2.2
Hz, 1 H), 2.21 (s, 3 H), 2.08 (dt, J = 15.2, 4.7 Hz, 1 H), 1.97 (bs, 1 H), 1.37 (s, 3 H).
13
C NMR (75 MHz, CDCl3, DEPT) δ C 208.5, 139.1, 138.4, 81.4; CH 131.4, 129.0 (2),
128.3, 126.5 (2), 64.0, 56.7, 42.5; CH2 67.2, 30.7; CH3 29.8, 25.2
S20
References:
(1) Tidwell, J. H.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 11797–11810.
(2) Grushin, V. V; Bensimon, C.; Alper, H. Inorg. Chem. 1994, 33, 4804–4806.
(3) Smonou, I.; Orfanopoulos, M. Synth. Comm. 1990, 20, 1387–1397.
(4) Ankala, S. V.; Fenteany, G. Tetrahedron Lett. 2002, 43, 4729–4732.
(5) Machotta, A. B.; Straub, B. F.; Oestreich, M. J. Am. Chem. Soc. 2007, 129,
13455–13463.
(6) Kajigaeashi, S.; Kakinami, T.; Okamoto, T.; Nakamura, H.; Fujikawa, M. Bull.
Chem. Soc. Jpn. 1987, 60, 4187–4189.
(7) Luche, J.-L.; Rodriguez-Hahn, L.; Crabbé, P. J. Chem. Soc. Chem. Comm. 1978,
601–602
(8) Banks, J. C.; Van Mele, D.; Frost, C. Tetrahedron Lett. 2006, 47, 2863–2866.
S21
O
Me
Me O
2a
(300 MHz, CDCl3)
S22
O
Me
Me O
2a
(75 MHz, CDCl3)
S23
O
Me
Me
Me O
2f
(300 MHz, CDCl3)
S24
O
Me
Me
Me O
2f
(75 MHz, CDCl3)
S25
O
Me Me
Me O
2e
(300 MHz, CDCl3 )
S26
O
Me Me
Me O
2e
(75 MHz, CDCl3)
S27
O
Br Me
Me O
2b
(300 MHz, CDCl 3)
S28
O
Br Me
Me O
2b
(75 MHz, CDCl3 )
S29
OTBS
Br
O H
S1
(300 MHz, CDCl3 )
S30
OTBS
Br
O H
S1
(75 MHz, CDCl3 )
S31
OTBS
Br
HO
S2
(300 MHz, CDCl3)
S32
OTBS
Br
HO
S2
(75 MHz, CDCl3 )
S33
OTBS
Br
S3
(300 MHz, CDCl3 )
S34
OTBS
Br
S3
(75 MHz, CDCl3 )
S35
OTBS
Br
Me
S4
(300 MHz, CDCl3)
S36
OTBS
Br
Me
S4
(75 MHz, CDCl3 )
S37
OH
Br
Me
S5
(300 MHz, CDCl3)
S38
OH
Br
Me
S5
(75 MHz, CDCl3 )
S39
O
Br
Me
MeO
2d
(300 MHz, CDCl3)
S40
O
Br
Me
MeO
2d
(75 MHz, CDCl3 )
S41
OTBS
Br
S6
(300 MHz, CDCl3)
S42
OTBS
Br
S6
(75 MHz, CDCl3)
S43
OH
Br
S7
(300 MHz, CDCl 3)
S44
OH
Br
S7
(75 MHz, CDCl3)
S45
O
Br
MeO
2c
(300 MHz, CDCl3)
S46
O
Br
MeO
2c
(75 MHz, CDCl3)
S47
OTBS
MeO
O H
S8
(300 MHz, CDCl3 )
S48
OTBS
MeO
O H
S8
(75 MHz, CDCl3)
S49
OTBS
MeO H
HO
S9
(300 MHz, CDCl3 )
S50
OTBS
MeO H
HO
S9
(75 MHz, CDCl3)
S51
OTBS
MeO H
S10
(300 MHz, CDCl 3)
S52
OTBS
MeO H
S10
(75 MHz, CDCl3)
S53
OTBS
MeO Me
S11
(300 MHz, CDCl 3)
S54
OTBS
MeO Me
S11
(75 MHz, CDCl3 )
S55
OH
MeO Me
S12
(300 MHz, CDCl 3)
S56
OH
MeO Me
S12
(75 MHz, CDCl3 )
S57
O
MeO Me
MeO
2h
(300 MHz, C6D6)
S58
O
MeO Me
MeO
2h
(75 MHz, C6D6 )
S59
OH
Br
Me
Me
S13
(300 MHz, CDCl3)
S60
OH
Br
Me
Me
S13
(75 MHz, CDCl3)
S61
O
Br
Me Me
Me
O
2g
(300 MHz, CDCl 3)
S62
O
Br
Me Me
Me
O
2g
(300 MHz, CDCl 3)
S63
O
H Me
Me OAc
O
3a
(300 MHz, CDCl3)
S64
O
H Me
Me OAc
O
3a
(75 MHz, CDCl 3)
S65
O
H Me
Me
Me OAc
O
3fa
(300 MHz, CDCl3)
S66
O
H Me
Me
Me OAc
O
3fa
(75 MHz, CDCl3)
S67
O
Me Me
Me OAc
O
3fb
(300 MHz, CDCl3 )
S68
O
Me Me
Me OAc
O
3fb
(75 MHz, CDCl3)
S69
O
Me
H Me
Me OAc
O
3e
(300 MHz, CDCl 3)
S70
O
Me
H Me
Me OAc
O
3e
(75 MHz, CDCl3)
S71
O
Br
H Me
Me OAc
O
3b
(300 MHz, CDCl3 )
S72
O
Br
H Me
Me OAc
O
3b
75 MHz, CDCl 3)
S73
O
Br
H Me
MeO OAc
3d
(300 MHz, CDCl3)
S74
O
Br
H Me
MeO OAc
3d
(75 MHz, CDCl 3)
S75
O
Br
H
MeO OAc
3c
(300 Mhz, CDCl 3)
S76
O
Br
H
MeO OAc
3c
(75 MHz, CDCl 3)
S77
O
H Me
MeO
MeO OAc
3h
(300 MHz, CDCl 3)
S78
O
H Me
MeO
MeO OAc
3h
(75 MHz, CDCl3)
S79
O
Br
Me Me
Me OAc
O
3g
(300 MHz, CDCl3)
S80
O
Br
Me Me
Me OAc
O
3g
(75 MHz, CDCl 3)
S81
OH
Br
H Me
Me OAc
O
S14
(300 MHz, CDCl3)
S82
OH
Br
H Me
Me OAc
O
S14
(75 MHz, CDCl 3)
S83
OH
Br
H Me
Me O
O
7
(300 MHz, CDCl3)
S84
OH
Br
H Me
Me O
O
7
(75 MHz, CDCl 3)
S85
OH
H Me
Me O
O
8
(300 MHz, CDCl3)
S86
OH
H Me
Me O
O
8
(75 MHz, CDCl 3)
S87

Cyclohexadienones

Uploaded by

Copyright:

Available Formats

Cyclohexadienones

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Cyclohexadienones

Uploaded by

Copyright:

Available Formats

Palladium-Catalyzed Reactions of Cyclohexadienones: Regioselective Cyclizations

Triggered by Alkyne Acetoxylation

Rodolfo Tello-Aburto and Andrew M. Harned*

University of Minnesota, Department of Chemistry, 207 Pleasant Street SE, Minneapolis,

Materials and Methods S2

General Procedure for Pd-Catalyzed Cyclization Reactions S14

Cyclization Products S14

Copies of NMR spectra S22

A well-stirred solution of p–cresol (108.14 mg, 1.0 mmol) in 1 mL of 2-butyn-1-ol was

A mixture of 2-bromo-4-methyl-phenol (0.12 mL, 1.0 mmol) and 2-butyn-1-ol (2 mL)

A well-stirred solution of 3-bromo-4-hydroxy benzaldehyde (1.94 g, 9.65 mmol) in 75

A literature procedure4 was implemented. A well-stirred solution of TBS ether S4 (68

A well-stirred solution of phenol S5 (65 mg, 0.27 mmol) in 2.5 mL of anhydrous

IR (neat) 2934, 1674, 1603, 1451, 1333, 1086, 828.1 cm-1

IR (neat) 3508, 2926, 1604, 1494, 1182, 1040, 755 cm-1

A solution of 2-methoxy-4-hydroxybenzaldehyde (500 mg, 3.28 mmol) in 30 mL of dry

MeO THF, 0 ºC MeO H

MeO H CH2Cl2, 0 ºC MeO H

A literature procedure3 was adapted. A well-stirred solution of alcohol S9 (299.7 mg,

MeO Me MeOH, 0 ºC MeO Me

A literature procedure6 was implemented. A well-stirred solution of 3,4-dimethylphenol

General Procedure for Pd-Catalyzed Cyclization Reactions. A mixture of the

Data for major compound (3fa)

Data for minor compound (3fb)

IR (neat) 2932, 1749, 1658, 1605, 1364, 1221 cm-1

IR (neat) 3418, 2964, 2928, 2893, 1703, 1648, 1088 cm-1

You might also like