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org/joc

Iridium-Catalyzed Asymmetric Ring Opening of Azabicyclic

Alkenes by Amines
Yuhua Long,† Dingqiao Yang,*,† Zhenming Zhang,† Yujuan Wu,† Heping Zeng,† and
Yu Chen*,‡
†
School of Chemistry and Environment, South China Normal University, Guangzhou 510006,
People’s Republic of China, and ‡Department of Chemistry and Biochemistry, Queens College,
City University of New York, 65-30 Kissena Boulevard, Flushing, New York 11367, United States

[email protected]; [email protected]
Received July 30, 2010

The enantioselective ring-opening reactions of azabicyclic alkenes with primary and secondary
aromatic amine nucleophiles are reported using an iridium catalyst generated in situ from 1.5 mol %
of [Ir(COD)Cl]2 and 3 mol % of (S)-BINAP. The reaction affords the corresponding trans-1,2-diamine
derivatives in moderate to good yields with moderate to high enantioselectivities (up to 97% ee). The
trans-configuration of the 1,2-diamino product 2g was confirmed by X-ray crystallography.

Introduction alkynes,8 organic halides,9 amines,10 Grignard reagents,11

methanol,12 and others.13 Iridium-catalyzed allylic substitution
Ring-opening reactions of oxa- and azabicyclic olefins are
is an efficient protocol for the construction of both carbon-
exceedingly important methods of great utility in synthetic
carbon bonds and carbon-heteroatom bonds providing a
chemistry. Recently, this area has been paid increasing
feasible way to generate multifunctional chiral building
attention and extensively investigated.1 Many parameters
blocks.14,15 Ring-opening reaction of azabenzonorbornadienes
have been examined for these reactions, including a variety
of metal catalysts such as Rh,2 Pd,3 Cu,4 and Ni5 etc., and
nucleophiles such as dialkylzincs,2a,6 organoboronic acids,7 (9) Hen, C. L.; Martin, S. F. J. Org. Chem. 2006, 71, 4810–4817.
(10) Cho, Y. H.; Zunic, V.; Senboku, H.; Olsen, M.; Lautens, M. J. Am.
Chem. Soc. 2006, 128, 6837–6846.
(1) For reviews, see: Rayabarapu, D. K.; Cheng, C. H. Acc. Chem. Res. (11) Cabrera, S.; Arrayas, R. G.; Alonso, I.; Carretero, J. C. J. Am. Chem.
2007, 40, 971–983. Soc. 2005, 127, 17938–17947.
(2) (a) Lautens, M.; Hiebert, S.; Renaud, J. L. Org. Lett. 2000, 2, 1971– (12) Webster, R.; Biong, C.; Lautens, M. J. Am. Chem. Soc. 2009, 131,
1973. (b) Cho, Y. H.; Tseng, N. W.; Senboku, H.; Lautens, M. Synthesis 444–445.
2008, 15, 2467–2475. (13) (a) John, J.; Anas, S.; Sajisha, V. S.; Viji, S.; Radhakrishnan, K. V.
(3) (a) Chen, C. L.; Martin, S. F. J. Org. Chem. 2006, 71, 4810–4817. (b) Tetrahedron Lett. 2007, 48, 7225–7227. (b) Wu, M. S.; Rayabarapu, D. K.;
Cabrera, S.; Gomez, A. R.; Carretero, J. C. Angew. Chem., Int. Ed. 2004, 43, Cheng, C. H. J. Org. Chem. 2004, 69, 8407–8412.
3944–3947. (14) For reviews, see: (a) Ohmura, T.; Hartwig, J. F. J. Am. Chem. Soc.
(4) (a) Arrayas, R. G.; Cabrera, S.; Carretero, J. C. Synthesis 2006, 7, 2002, 124, 15164–15165. (b) Alexakis, A.; Hajjaji, S. E.; Polet, D.; Rathgeb,
1205–1219. (b) Arrayas, R. G.; Cabrera, S.; Carretero, J. C. Org. Lett. 2005, X. Org. Lett. 2007, 9, 3393–3395. (c) Yamashita, Y.; Gopalarathnam, A.;
7, 219–221. Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 7508–7509. (d) Kanayama, T.;
(5) (a) Feng, C. C.; Nandi, M.; Sambaiah, T.; Cheng, C. H. J. Org. Chem. Yoshida, K.; Miyabe, H.; Kimachi, T.; Takemoto, Y. J. Org. Chem. 2003, 68,
1999, 64, 3538–3543. (b) Li, L. P.; Rayabarapu, D. K.; Nandi, M.; Cheng, 6197–6201. (e) Weix, D. J.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 7720–
C. H. Org. Lett. 2003, 5, 1621–1624. 7721. (f) Nomura, N.; Komiyama, S.; Kasugai, H.; Saba, M. J. Am. Chem.
(6) (a) Cabrera, S.; Alonso, L.; Arrayas, R.; Familiar, O.; Carretero, J. Soc. 2008, 130, 812–814. (g) Alexakis, A.; Hajjaji, S. E.; Polet, D.; Rathgeb,
Phosphorus, Sulfur Silicon Relat. Elem. 2005, 180, 1513–1514. (b) Ogura, T.; X. Org. Lett. 2007, 9, 3393–3395. (h) Polet, D.; Alexakis, A. Org. Lett. 2005,
Yoshida, K.; Yanagisawa, A.; Imamoto, T. Org. Lett. 2009, 11, 2245–2248. 7, 1621–1624. (i) Kanayama, T.; Yoshida, K.; Miyabe, H.; Kimachi, T.;
(7) Lautens, M.; Dockendorff, C. Org. Lett. 2003, 5, 3695–3698. Takemoto, Y. J. Org. Chem. 2003, 68, 6197–6201. (j) Woodward, S. Angew.
(8) Nishimura, T.; Tsurumaki, E.; Kawamoto, T.; Guo, X. X.; Hayashi, Chem., Int. Ed. 2005, 42, 5560–5562. (k) Hayashi, T.; Yamasaki, K. Chem.
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DOI: 10.1021/jo101470r Published on Web 10/13/2010 J. Org. Chem. 2010, 75, 7291–7299 7291
r 2010 American Chemical Society
JOC Article Long et al.

represents a type of allylic substitution reaction in which the TABLE 1. Ligand Optimization for Iridium-Catalyzed Asymmetric
reaction proceeds under relatively mild conditions, leading to a Ring-Opening of N-Boc-Azabenzonorbornadiene 1 with N-Methylanilinea
variety of 1,2-diamino compounds in both high yields and
excellent enantioselectivities. Lautens and co-workers16 have
extensively investigated Rh-catalyzed asymmetric ring-opening
reactions of azabenzonorbornadienes with amines (up to 99%
ee) and successfully employed them in the preparation of new
chiral ligands17 and analgesic compounds.18 Recently, we have
reported Rh-19 and Ir-catalyzed20 asymmetric ring-opening
reactions of N-Boc-azabenzonorbornadiene with N-substi-
tuted piperazine nucleophiles in high yields and high enantio-
selectivities. Our interest in generating carbon-nitrogen bonds
has prompted us to expand the scope of the reaction to include
primary aromatic amine as well as cyclic and acyclic secondary
amine-induced ring openings of azabicyclic alkenes for an
efficient access to trans-1,2-diamine moieties with high regio-,
diastereo-, and enantioselectivities. These methods offer poten-
tially useful synthetic routes to trans-1,2-diamines which are the
scaffolds for chiral ligands21 and valuable intermediates for
total synthesis of bioactive compounds.22
In this paper, we report the full details of the catalytic asym- entry [Ir(COD)Cl]2 ligand yieldb (%) eec (%)
metric ring-opening reactions of N-substituted azabenzonorbor-
1 1.0 mol % 2 mol % DPPF 71 0
nadienes 1, 3, and 5 with a wide variety of amines in the presence 2 1.5 mol % 3 mol % DPPF 86 0
of iridium catalysts. The reaction affords the corresponding 3 2.0 mol % 4 mol % DPPF 83 0
trans-1,2-diamine derivatives in moderate to good yields with 4 1.5 mol % 3 mol % (R)-(S)-PPF-PtBu2 10 20
moderate to excellent enantioselectivities (up to 97% ee). 5 1.5 mol % 3 mol % (S)-(R)-NMe2- nr
PPh2-Mandyphos
6 1.5 mol % 3 mol % (S)-BINAP 56 84
Results and Discussion 7 1.5 mol % 3 mol % (S)-p-Tol-BINAP 10 70
8 1.5 mol % 3 mol % L1 nr
The substrates 1, 3, and 5 were prepared according to the 9 1.5 mol % 1.5 mol % (S)-BINAP 6 43
literature procedures.20a,7,16b An achiral ligand 1,10 -bis(diphenyl- 10 1.5 mol % 4.5 mol % (S)-BINAP 30 62
phosphino)ferrocene (DPPF) was first chosen to validate the a
The reaction was carried out with 1 (0.21 mmol) and 3.0 equiv of
N-methylaniline (0.63 mmol) in THF (2.0 mL) at 80 °C (oil bath
(15) For selected recent examples on iridium-catalyzed allylations, see: temperature). bIsolated yield after silica gel column chromatography.
c
(a) Raskatov, J. A.; Spiess, S.; Gnamm, C.; Broedner, K.; Rominger, F.; Determined by HPLC with a Chiralcel AD-H column.
Helmchen, G. Chem.;Eur. J. 2010, 16, 6601–6615. (b) Spiess, S.; Raskatov,
J. A.; Gnamm, C.; Broedner, K.; Helmchen, G. Chem.;Eur. J. 2009, 15, catalytic activity of the iridium complex in the ring-opening
11087–11090. (c) Spiess, S.; Welter, C.; Franck, G.; Taquet, J.-P.; Helmchen,
G. Angew. Chem., Int. Ed. 2008, 47, 7652–7655. (d) Helmchen, G.; Dahnz, A.; reactions of N-Boc-azabenzonorbornadiene with N-methylani-
Duebon, P.; Schelwies, M.; Weihofen, R. Chem. Commun. 2007, 675–691. line. In the presence of 1 mol % of [Ir(COD)Cl]2 and 2 mol % of
(16) (a) Cho, Y. H.; Fayol, A.; Lautens, M. Tetrahedron: Asymmetry DPPF, the desired ring-opening product was obtained in a 71%
2006, 17, 416–427. (b) Lautens, M.; Fagnou, K.; Zunic, V. Org. Lett. 2002, 4,
3465–3468. (c) McManus, A. H.; Fleming, M. J.; Lautens, M. Angew. Chem., yield (Table 1, entry 1). The yield was increased to 86% when 1.5
Int. Ed. 2007, 46, 433–436. mol % of [Ir(COD)Cl]2 and 3 mol % of DPPF were employed
(17) (a) Lucet, D.; Le Gall, T.; Mioskowski, C. Angew. Chem., Int. Ed. 1998,
37, 2580–2627. (b) Hoppe, D.; Hense, T. Angew. Chem., Int. Ed. Engl. 1997, 36,
(Table 1, entry 2). However, further increase of the catalyst
2282–2316. (c) Beak, P.; Basu, A.; Gallagher, D. J.; Park, Y. S.; Thayumanavan, loading did not improve the yield (Table 1, entry 3). Several
S. Acc. Chem. Res. 1996, 29, 552–560. (d) Trost, B. M.; Van Vranken, D. L. chiral ligands such as (R)-(S)-PPF-PtBu2, (S)-(R)-NMe2-PPh2-
Chem. Rev. 1996, 96, 395–422. (e) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J.
Am. Chem. Soc. 1992, 114, 9327–9343. (f) Trost, B. M.; Bunt, R. C.; Lemoine, Mandyphos, (S)-BINAP, (S)-p-Tol-BINAP, and L1 were then
R. C.; Calkins, T. L. J. Am. Chem. Soc. 2000, 122, 5968–5976. examined. From Table 1, we can see that (S)-BINAP gave
(18) (a) Szmuszkovicz, J.; VonVoigtlander, P. F.; Kane, M. P. J. Med. Chem. the best yield and enantioselectivity when the molar ratio of
1981, 24, 1230–1236. (b) Cowan, A.; Gmerek, D. E. Trends Pharmacol. Sci. 1986,
7, 69–72. (c) Millan, M. J. Trends Pharmacol. Sci. 1990, 11, 70–76. (S)-BINAP to iridium was 2:1 (Table 1, entry 6). While the
(19) (a) Xie, L.; Yang, D. Q.; Zhao, S. Q.; Wang, H.; Liang, L. H.; Luo, molar ratio of (S)-BINAP to iridium changed to 1:1 or 3:1, the
R. S. Chin. Chem. Lett. 2007, 18, 127–129. (b) Liu, E. C.; Yang, D. Q.; Han,
Y. F.; Dong, J. X. Chin. Chem. Lett. 2006, 17, 717–719.
ring-opening reaction gave a lower yield and enantioselectivity
(20) (a) Yang, D. Q.; Long, Y. H.; Wang, H.; Zhang, Z. M. Org. Lett. (Table 1, entries 9 and 10). Other ligands such as (R)-(S)-PPF-
2008, 10, 4723–4726. (b) Long, Y.-H.; Zhao, S.-Q.; Zeng, H.-P.; Yang, D.-Q. PtBu2, (S)-(R)-NMe2-PPh2-Mandyphos, (S)-p-Tol-BINAP,
Catal. Lett. 2010, 138, 124–133. (c) Long, Y.-H.; Yang, D.-Q.; Zeng, H.-P.;
Xie, L.; Wu, L.-H; Mo, H.-H.; Zuo, X.-J. Chin. J. Chem. 2010, 28, 235–242. and L1 gave either unsatisfactory results (Table 1, entries 4
(21) (a) Fache, F.; Schulz, E.; Tommasino, M. L.; Lemaire, M. Chem. and 7) or no reaction (Table 1, entries 5 and 8).
Rev. 2000, 100, 2159–2232. (b) Jacobsen, E. N.; Zhang, W.; Muci, A. R.; In order to obtain better yields and higher enantioselec-
Ecker, J. R.; Deng, L. J. Am. Chem. Soc. 1991, 113, 7063–7064. (c) Zhang,
W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990, tivities for the asymmetric ring-opening reaction of aza-
112, 2801–2803. benzonorbornadiene with amine nucleopiles, a number of
(22) (a) Alexander van Vliet, L.; Tepper, P. G.; Dijkstra, D.; Damsma, G.;
Wikstrom, H.; Pugsley, T. A.; Akunne, H. C.; Heffner, T. G.; Glase, S. A.;
parameters including solvents, temperature, and additives
Wise, L. D. J. Med. Chem. 1996, 39, 4233–4237. (b) Degnan, A. P.; Meyers, have therefore been investigated. It was found that solvents
A. I. J. Org. Chem. 2000, 65, 3503–3512. (c) Marquet, A. Pure Appl. Chem. played a significant role in improving both reactivity
1993, 65, 1249–1252. (d) Hettinger, T. P.; Craig, L. C. Biochemistry 1970, 9,
1224–1232. (e) Umezawa, H.; Maeda, K.; Takeuchi, T.; Okami, Y. J. and enantioselectivity. The optimal solvent turned out to
Antibiot. Ser. A 1996, 19, 200–209. be tetrahydrofuran (THF). Iridium-catalyzed asymmetric
7292 J. Org. Chem. Vol. 75, No. 21, 2010
Long et al.
JOC Article
TABLE 2. Condition Screening for Iridium-Catalyzed Asymmetric TABLE 3. Iridium-Catalyzed Asymmetric Ring-Opening of 1 with
Ring-Opening Reaction of N-Boc-Azabenzonorbornadiene 1 with Secondary Amine Nucleophilesa
N-Methylanilinea

entry solvent additive time (h) yieldb (%) eec (%)

1 CH3CN 48 79 56
2 toluene 48 19 43
3 CH2Cl2 48 21 87
4 dioxane 48 39 61
5 THP 48 68 64
6 THF 48 56 84
7 THFd 48 trace
8 THFe 48 52 78
9 THF NH4I 48 12.5 60
10 THF NH4Br 48 trace
11 THF Bu4NI 48 78 62
12 THF Et3NHCl 48 13 80
a
The reaction was carried out with 1 (0.21 mmol) and 3.0 equiv of
N-methylaniline (0.63 mmol) in solvent (2.0 mL) at 80 °C (oil bath
temperature) in the presence of [Ir(COD)Cl]2 (1.5 mol %) and (S)-BINAP
(3 mol %). bIsolated yield after silica gel column chromatography.
c
Determined by HPLC with a Chiralcel AD-H column. dOil bath tempera-
ture is 60 °C. eOil bath temperature is 100 °C.

ring-opening reaction of N-Boc-azabenzonorbornadiene 1

with N-methylaniline afforded the corresponding product
2a in a 56% yield and 84% ee in THF (Table 2, entry 6). The
same reaction afforded the expected product 2a in a 79%
yield and 56% ee in CH3CN (Table 2, entry 1). In CH2Cl2,
the desired product 2a was obtained only in a low yield
(21%) though with a high enantioselectivity (87% ee)
(Table 2, entry 3). In addition, both modest yields and
enantioselectivities were obtained when other solvents such
as toluene, dioxane, and THP were employed (Table 2,
entries 2, 4, and 5). Temperature also plays a crucial role
in this ring-opening reaction. Although a 56% yield and
an 84% ee were obtained at 80 °C (Table 2, entry 6), only
a trace amount of ring-opening product was obtained at
60 °C after 48 h (Table 2, entry 7). On the other hand, the a
The reaction was carried out with 1 (0.21 mmol) and 3.0 equiv of
reaction afforded the desired product in a lower yield and amine (0.63 mmol) in THF (2 mL) at 80 °C (oil bath temperature) in the
presence of [Ir(COD)Cl]2 (1.5 mol %) and (S)-BINAP (3 mol %).
enantioselectivity when the temperature was increased to b
Isolated yield after silica gel column chromatography. cDetermined
100 °C (Table 2, entry 8). The role of ammonium halide by HPLC with a chiral stationary column (Chiralcel AD-H column for
additives was also explored. It turned out they were not 2a, 2b, 2c, 2f, and 2g; Chiralcel OD-H column for 2h, 2i, 2j, and 2k). dThe
necessary in this reaction (Table 2, entries 9-12). reaction solvent is THP at 100 °C (oil bath temperature).
On the basis of these studies, the asymmetric ring opening of
1 with a variety of N-alkylanilines and aliphatic amines was In order to extend the scope of this reaction to other sub-
explored under the optimal reaction conditions: 1.5 mol % of strates, we then examined the ring opening of 6,7-dimethoxy-
[Ir(COD)Cl]2 and 3 mol % of (S)-BINAP in THF at 80 °C. In N-Boc-azabenzonorbornadiene (3) by amines. An obvious
general, N-alkylanilines reacted with 1 to give the correspond- increase in terms of enantioselectivity was observed when
ing products in higher yields and enantioselectivities (Table 3, N-methylaniline instead of N-ethylaniline was used as the
entries 1-8) than substituted aliphatic amines (Table 3, entries nucleophile (Table 4, entries 1 and 2). Only moderate
9-11). The substituent on the aniline nitrogen has a significant enantioselectivities were obtained when secondary aliphatic
impact on both the chemical yield and enantioselectivity amines such as 1,2,3,4-tetrahydroquinoline and 1-phenylpiper-
(Table 3, entries 1-4). Due to the steric bulkiness of the cyclo- azine were employed (Table 4, entries 3 and 4). No ring-opening
hexyl group, the ring-opening reaction by N-cyclohexylaniline product of substrate 3 was observed when piperidine was used
did not afford any desired product (Table 3, entry 4). A similar as the nucleophile (Table 4, entry 5).
result was observed when 2-chloro-N-methylaniline was used The asymmetric ring-opening reactions of N-Ts-azaben-
as the nucleophile in the ring opening (Table 3, entry 5). The zonorbornadiene 5 with secondary amines were also inves-
yields decreased in the case of 4-nitro- or 4-bromo-N-methyl- tigated. It was known that these ring-opening reactions
aniline nucleophiles, presumably due to the effect of the electron- afforded the products in high yield (90%) but low enantio-
withdrawing substitutents (Table 3, entries 6 and 7). selectivity (10% ee) in the presence of a rhodium catalyst
J. Org. Chem. Vol. 75, No. 21, 2010 7293
JOC Article Long et al.

TABLE 4. Iridium-Catalyzed Asymmetric Ring Opening of 3 with TABLE 5. Iridium-Catalyzed Asymmetric Ring-Opening of 5 with
Secondary Amine Nucleophilesa Secondary Amine Nucleophilesa

a
The reaction was carried out with 5 (0.20 mmol) and 3.0 equiv of
amine (0.60 mmol) in THF (2.0 mL) at 80 °C (oil bath temperature) in
the presence of [Ir(COD)Cl]2 (1.5 mol %) and (S)-BINAP (3 mol %).
b
Isolated yield after silica gel column chromatography. cDetermined by
a
The reaction was carried out with 3 (0.20 mmol) and 3.0 equiv HPLC with a chiral stationary column (Chiralcel AD-H column for 6c;
of amine (0.60 mmol) in THF (2 mL) at 80 °C (oil bath temperature) in Chiralcel OD-H column for 6a and 6b).
the presence of [Ir(COD)Cl]2 (1.5 mol %) and (S)-BINAP (3 mol %).
b
Isolated yield after silica gel column chromatography. cDetermined by
HPLC with a chiral stationary column (Chiralcel AD-H column for 4a;
Chiralcel OD-H column for 4b, 4c and 4d). dThe reaction solvent is THP TABLE 6. Iridium-Catalyzed Asymmetric Ring-Opening of Azabicyc-
at 100 °C (oil bath temperature). lic Alkenes with Primary Aromatic Amine Nucleophilesa

system.10 To our delight, the ring opening of 5 with N-methyl-

aniline afforded the corresponding product 6a not only in a high
yield (92%) but also in a higher enantioselectivity (70% ee)
in the presence of 1.5 mol % of [Ir(COD)Cl]2 and 3 mol % of
(S)-BINAP (Table 5, entry 1). The enantioselectivity is even
better when N-ethylaniline is used as the nucleophile compared
to N-methylaniline though with a slightly lower yield (Table 5,
entry 2). The best results of 88% yield and 86% ee were obtained
when 3-methyl-N-methylaniline was used as the nucleophile
(Table 5, entry 3). However, the reaction with an aliphatic
amine nucleophile, N-phenylpiperazine, did not afford any ring-
opening product (Table 5, entry 4).
Both aniline and 1-aminonaphthalene proved to be effi-
cient nucleophiles in the rhodiun-catalyzed asymmetric ring-
opening reaction of azabicyclic alkenes.10 This encouraged
us to screen primary aromatic amine nucleophiles, as well.
The results summarized in Table 6 show that the nature of
the substituent group on the nitrogen in the azabicyclic
alkene substrate plays a significant role in the enantioselec-
tivity of the products. For example, the ee value of the
products decreased when a Boc group was present in sub-
strate 1, while the presence of a Ts group in substrate 5
a
enhanced the ee value (Table 6, entries 2 and 3). It was The reaction was carried out with 1 or 5 (0.20 mmol) and 3.0 equiv of
observed that both the substituted groups on nitrogen of the amine (0.60 mmol) in THF (2.0 mL) at 100 °C (oil bath temperature) in
azabicyclic alkenes and the electronic effect of nucleophiles the presence of [Ir(COD)Cl]2 (1.5 mol %) and (S)-BINAP (3 mol %).
b
Isolated yield after silica gel column chromatography. cDetermined by
were found to have remarkable impacts on the enantioselec- HPLC with a chiral stationary column (Chiralcel AD-H column for 2l,
tivity of the ring-opening reaction. Nucleophiles with elec- 6f, 6g, and 6h; Chiralcel OD-H column for 2m and 6e).
tron-rich functional groups on the benzene ring such as
2,4-dimethoxyaniline and 4-propylaniline gave moderate electron-withdrawing Br group was present on the aniline
yields with excellent enantioselectivities (up to 97% ee) benzene ring, both chemical yield and enantioselectivity
(Table 6, entries 4 and 5). On the other hand, when a slightly decreased dramatically (Table 6, entry 6).
7294 J. Org. Chem. Vol. 75, No. 21, 2010
Long et al.
JOC Article
trans-1,2-diamino product 2 is subsequently released and
the iridium complex A is regenerated.

Conclusions
We have developed an asymmetric ring-opening reaction of
N-subsitituted azabicyclic alkenes by a number of primary and
secondary amine nucleophiles in the presence of [Ir(COD)Cl]2/
(S)-BINAP catalyst. It provides an efficient and practical access
to the optically active 1,2-diamine derivatives in moderate to
good yields and enantioselectivities under mild conditions. Our
results further reveal that the nature of the chiral ligand has a
significant impact on this ring-opening reaction. The new
method is significant in terms of the low cost for the ligands
FIGURE 1. ORTEP plot for 2g. and facile manipulation compared to literature precedents. An
investigation on the biological and pharmaceutical activities of
the products is in progress. Studies on further expansion of the
SCHEME 1. Working Hypothesis for the Asymmetric Ring
Opening of N-Boc-Azabenzonorbornadiene 1 with a Secondary scope and synthetic utility of this Ir-catalyzed reaction are also
Amine Nucleophile being pursued in our laboratory.

Experimental Section
General. THF, THP, dioxane, and toluene were distilled from
sodium benzophenone ketyl immediately prior to use. CH3CN
and CH2Cl2 were distilled from calcium hydride. Azabenzonor-
bornadienes 1,20a 3,7 5,16b and [Ir(COD)Cl]220a were prepared
according to the reported procedures. All flasks were flame-
dried under a stream of nitrogen and cooled to room tempera-
ture before use. Solvents and solutions were transferred with
syringes and cannulae using standard inert atmosphere tech-
niques. All 1H and 13C NMR spectra were recorded at 400 and
100 MHz, respectively, using CDCl3 as a solvent. The chemical
shifts of all 1H and 13C NMR spectra are referenced to the
residual signal of CDCl3 (δ 7.27 ppm for the 1H NMR spectra
and δ 77.23 ppm for the 13C NMR spectra). Spectral features are
tabulated in the following order: chemical shift (δ, ppm); multi-
plicity (s-singlet, d-doublet, t-triplet, q-quadruplet, m-complex
multiplet, br-broad); coupling constants (J, Hz); number of pro-
tons. IR spectra were obtained using a KBr pellet or using a
neat film on a NaCl plate. MS spectra were recorded using ESI.
The melting points are uncorrected.
General Procedure (I) for the Asymmetric Ring-Opening Reac-
tions of N-Boc-Azabenzonorbornadiene 1 with Secondary Amine
Nucleophiles. A 5 mL round-bottom flask fitted with a reflux
condenser was flame-dried under a stream of nitrogen and cooled
The absolute configuration of ring-opened product 2g was to room temperature. [Ir(COD)Cl]2 (2.1 mg, 1.5 mol %) and
demonstrated by X-ray crystallography. The single crystal (S)-BINAP (3.9 mg, 3 mol %) were added, followed by the addi-
was obtained by solvent evaporation from a solution con- tion of anhydrous THF (2.0 mL). After the mixture was stirred
sisting of dichloromethane, petroleum ether, and ethyl ace- for 10 min at room temperature, N-Boc-azabenzonorbornadiene
1 (50 mg, 0.21 mmol) was added and the temperature of the oil
tate. Its configuration was assigned as (1R,2R) and confirmed
bath was increased to 80 °C. On the first sign of reflux, nucleo-
as 1,2-trans-configuration, as shown in Figure 1. It is obvious phile (3-5 equiv to 1) was added. The reaction was stirred at
that the reaction favors the formation of trans-1,2-diamino 80 °C until completion as monitored by thin layer chromatogra-
products. phy. After the reaction mixture was cooled to room temperature,
On the basis of our studies, a working hypothesis is shown in the solvent was removed in vacuo and the residue was purified by
Scheme 1. First, the chiral dimeric iridium complex A is formed. column chromatography on silica gel (200-300 mesh) to give the
The nitrogen atom and the double bond of N-Boc-azabenzo- desired product.
norbornadiene 1 are then reversibly coordinated to the iridium (1R,2R)-[2-(Methylphenylamino)-1,2-dihydronaphthalen-1-yl]-
center of the catalyst to give the intermediate B. In this step, carbamic acid tert-butyl ester (2a). Following the general proce-
the intermediate B containing a larger Boc group is less dure (I), 2a was obtained as a white solid (40.2 mg, 56%): Rf =
0.24 on silica gel (ethyl acetate/petroleum ether = 1:20, v/v); mp
stable than the counterpart containing a relatively smaller
160-161 °C; ee was determined to be 84% using HPLC analysis
Ts group. Insertion of the iridium into the C-N bond of on a Chiralcel AD column (hexane/2-propanol = 90/10, 0.5 mL/
B forms C. Nucleophilic attack of C by an amine nucleo- min, λ = 254 nm); retention times were 11.4 min (minor) and 12.5
phile occurs in an SN20 displacement of the iridium catalyst min (major); [R]20D = -31.8 (c = 1.00, CHCl3); IR (KBr, cm-1)
with an inversion of configuration. Electron-rich amine 3380(s), 3063(w), 2976(w), 2819(w), 1688(s), 1575 (s), 1525(m),
nucleophiles are beneficial for the nucleophilic attack. The 1406(m), 1178(s), 1050(w), 745(m); 1H NMR (400 MHz, CDCl3)

J. Org. Chem. Vol. 75, No. 21, 2010 7295

JOC Article Long et al.

δ 7.34 (d, J = 6.4 Hz, 1H), 7.21 (t, J = 7.6 Hz, 3H), 7.10 (d, J = (d, J=9.2 Hz, 1H), 2.95 (s, 3H), 1.27 (s, 9H); 13C NMR (100 MHz,
5.2 Hz, 1H), 6.85 (d, J = 7.6 Hz, 2H), 6.72 (t, J = 6.0 Hz, 1H), CDCl3) δ 155.2, 154.4, 137.3, 134.3, 132.3, 131.0, 128.5, 128.4,
6.61 (d, J = 5.2 Hz, 1H), 5.93 (d, J = 9.6 Hz, 1H), 5.20 (t, J = 127.3, 127.1, 126.3, 126.0, 111.2, 79.9, 60.5, 52.3, 33.8, 28.2;
10.0 Hz, 1H), 4.79 (d, J = 10.0 Hz, 1H), 4.51 (d, J = 9.2 Hz, 1H), MS (ESI) calcd m/z for C22H25N3O4 (Mþ) 395.18, found 418.24
2.83 (s, 3H), 1.34 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 155.4, (M þ Na)þ. Anal. Calcd for C22H25N3O4: C, 66.82; H, 6.37; N,
150.1, 135.8, 130.0, 129.1, 128.0, 127.9, 126.6, 125.8, 121.0, 117.1, 10.63. Found: C, 66.69; H, 6.20; N, 10.33.
114.8, 113.6, 79.5, 60.7, 52.4, 33.0, 28.3; MS (ESI) calcd m/z for (1R,2R)-{2-[(4-Bromophenyl)methylamino]-1,2-dihydronaphtha-
C22H26N2O2 (Mþ) 350.20, found 351.03 (M þ H)þ. Anal. Calcd len-1-yl}carbamic acid tert-butyl ester (2g). Following the general
for C22H26N2O2: C, 75.40; H, 7.48; N, 7.99. Found: C, 75.69; procedure (I), 2g was obtained as a white solid (25.6 mg, 29%):
H, 7.20; N, 8.23. Rf = 0.16 on silica gel (ethyl acetate/petroleum ether = 1:25, v/v);
(1R,2R)- [2-(Ethylphenylamino)-1,2-dihydronaphthalen-1-yl]- mp 179-181 °C; ee was determined to be 65% using HPLC
carbamic acid tert-butyl ester (2b). Following the general proce- analysis on a Chiralcel AD column (hexane/2-propanol = 90/10,
dure (I), 2b was obtained as a white solid (34.4 mg, 45%): Rf = 0.5 mL/min, λ = 254 nm); retention times were 10.6 min (minor)
0.19 on silica gel (ethyl acetate/petroleum ether = 1:25, v/v); mp and 11.6 min (major)l [R]20D = -78.3 (c = 1.00, CHCl3); IR (KBr,
128-129 °C; ee was determined to be 76% using HPLC analysis cm-1) 3374(m), 3043(m), 2963(m), 2920(w), 1682(s), 1520 (s),
on a Chiralcel AD-H column (hexane/2-propanol = 95/5, 0.5 1495(s), 1366(m), 1108(m), 783(m); 1H NMR (400 MHz, CDCl3)
mL/min, λ = 254 nm); retention times were 14.4 min (minor) δ 7.32-7.21 (m, 4H), 7.11 (d, J = 6.0 Hz 1H), 6.73 (d, J = 8.8 Hz,
and 21.3 min (major); [R]20D = -56.5 (c = 1.00, CHCl3); IR 2H), 6.61 (dd, J = 12.0 Hz, 7.6 Hz, 1H), 5.87 (dd, J=12.4 Hz,
(KBr, cm-1) 3355(w), 3248(w), 2975 (w), 2927(w), 1696(s), 6.8 Hz, 1H), 5.16 (t, J = 9.6 Hz, 1H), 4.67 (d, J = 9.6 Hz, 1H), 4.52
1596(s), 1505(s), 1365(m), 1249(w), 1116(s), 987(m), 781(w), (d, J = 8.8 Hz, 1H), 2.78 (s, 3H), 1.34 (s, 9H); 13C NMR (100 MHz,
745(m), 642(w); 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J = CDCl3) δ 155.2, 149.0, 135.4, 132.6, 131.7, 130.2, 129.0, 128.1,
6.8 Hz, 1H), 7.26 (t, J = 8. 0 Hz, 3H), 7.13 (d, J = 6.4 Hz, 1H), 128.0, 126.8, 125.9, 115.1, 108.8, 79.6, 60.8, 52.2, 33.2, 28.2; MS
6.91 (d, J = 8.4 Hz, 2H), 6.75 (t, J = 7.2 Hz, 1H), 6.65 (dd, J = (ESI) calcd m/z for C22H25BrN2O2 (Mþ) 428.11, found 429.03
11.6 Hz, 8.0 Hz, 1H), 6.00 (dd, J = 12.0 Hz, 6.8 Hz, 1H), 5.20 (t, (M þ H)þ. Anal. Calcd for C22H25BrN2O2: C, 61.54; H, 5.87; N,
J = 9.2 Hz, 1H), 4.74 (d, J = 8.4 Hz, 1H), 4.63 (d, J = 8.8 Hz, 6.52. Found: C, 61.23; H, 5.62; N, 6.86.
1H), 3.32 (q, 2H), 1.43 (s, 9H), 1.11 (t, J = 6.8 Hz, 3H); 13C (1R,2R)-[2-(3,4-Dihydro-2H-quinolin-1-yl)-1,2-dihydronaphtha-
NMR (100 MHz, CDCl3) δ 155.2, 148.3, 135.5, 132.6, 130.2, len-1-yl]carbamic acid tert-butyl ester (2h). Following the general
129.2, 128.8, 128.1, 128.0, 126.8, 125.9, 121.7, 116.9, 114.7, 79.6, procedure (I), 2h was obtained as a white solid (51.4 mg, 65%):
61.0, 33.2, 28.3, 13.9; MS (ESI) calcd m/z for C23H28N2O2 (Mþ) Rf = 0.25 on silica gel (ethyl acetate/petroleum ether = 1:25, v/v);
364.22, found 364.97. Anal. Calcd for C23H28N2O2: C, 75.79; H, mp 120-121 °C; ee was determined to be 75% using HPLC
7.74; N, 7.69. Found: C, 75.69; H, 7.71; N, 7.92. analysis on a Chiralcel OD-H column (hexane/2-propanol = 90/
(1R,2R)-[2-(Allylphenylamino)-1,2-dihydronaphthalen-1-yl]- 10, 0.5 mL/min, λ = 254 nm); retention times were 9.5 min (major)
carbamic acid tert-butyl ester (2c). Following the general pro- and 12.8 min (minor); [R]20D = -56.4 (c = 1.00, CHCl3); IR (KBr,
cedure (I), 2c was obtained as a white solid (22.2 mg, 28%): cm-1) 3372(s), 2927(w), 1688(w), 2898(m), 1600(w), 1499(m),
Rf = 0.19 on silica gel (ethyl acetate/petroleum ether = 1:25, v/v); 1365(w), 1301(w), 1250(w), 1169(m), 1048(w), 783(w), 742(w); 1H
mp 111-113 °C; ee was determined to be 69% using HPLC NMR (400 MHz, CDCl3) δ 7.36 (d, J = 6.4 Hz, 1H), 7.24-7.21 (m,
analysis on a Chiralcel AD column (hexane/2-propanol = 95/5, 1H), 7.10 (d, J = 6.8 Hz, 1H), 7.02 (t, J = 7.8 Hz, 1H), 6.96 (d, J =
0.5 mL/min, λ = 254 nm); retention times were 14.7 min (minor) 7.2 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.63-6.56 (m, 2H), 5.91 (d,
and 18.9 min (major); [R]20D = -56.1 (c = 1.00, CHCl3); IR (KBr, J = 9.6 Hz, 1H), 5.28 (t, J = 9.8 Hz, 1H), 4.80 (d, J = 9.6 Hz, 1H),
cm-1) 3356(w), 2975(m), 2927(m), 1709(s), 1597(m), 1503(m), 4.62 (s, 1H), 3.22 (s, 2H), 2.72 (t, J = 6.4 Hz, 2H), 1.94-1.80 (m,
1456(w), 1367(s), 1332(s), 1252(s), 1168(s), 1074(m), 858(w), 2H), 1.35 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 155.5, 145.4,
782(w), 747(m), 694(w), 542(w); 1H NMR (400 MHz, CDCl3) 136.0, 132.8, 130.1, 129.5, 128.0, 127.8, 126.9, 126.6, 126.3, 125.9,
δ 7.31 (d, J = 7.2 Hz, 1H), 7.27-7.18 (m, 3H), 7.11 (d, J = 6.4 Hz, 123.6, 116.1, 111.2, 79.5, 58.3, 51.7, 43.5, 28.3, 28.2, 22.3; MS (ESI)
1H), 6.88 (d, J = 7.6 Hz, 2H), 6.72 (t, J = 7.0 Hz, 1H), 6.61 (d, J = calcd m/z for C24H28N2O2 (Mþ) 376.22, found 399.33 (M þ Na)þ;
9.6 Hz, 1H), 5.98 (d, J = 9.2 Hz, 1H), 5.78-5.73 (m, 1H), 5.16 (d, Anal. Calcd for C24H28N2O2: C, 76.56; H, 7.50; N, 7.44. Found: C,
J = 8.4 Hz, 1H), 5.12 (d, J = 6.0 Hz, 1H), 5.07 (d, J = 10.0 Hz, 76.31; H, 7.18; N, 7.63.
1H), 4.81 (d, J = 6.4 Hz, 1H), 4.58 (d, J = 6.8 Hz, 1H), 3.84 (s, (1R,2R)-[2-(3,4-Dihydro-1H-isoquinolin-2-yl)-1,2-dihydro-
2H), 1.37 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 155.2, 148.4, naphthalen-1-yl]carbamic acid tert-butyl ester (2i). Following the
135.7, 135.4, 132.5, 130.0, 129.0, 128.7, 128.1, 128.0, 126.7, 124.8, general procedure (I), 2i was obtained as colorless oil (22.9 mg,
117.1, 115.7, 114.2, 79.5, 59.7, 52.3, 29.7, 28.3; MS (ESI) calcd m/z 29%): Rf =0.37 on silica gel (ethyl acetate/petroleum ether=1:6,
for C24H28N2O2 (Mþ) 376.22, found 399.24 (M þ Na)þ. Anal. v/v); ee was determined to be 64% using HPLC analysis on a
Calcd for C24H28N2O2: C, 76.56; H, 7.50; N, 7.44. Found: C, 76.69; Chiralcel OD-H column (hexane/2-propanol = 90/10, 0.5 mL/
H, 7.80; N, 7.23. min, λ = 254 nm); retention times were 10.2 min (major) and
(1R,2R)-{2-[Methyl-(4-nitrophenyl)amino]-1,2-dihydronaphtha- 12.5 min (minor); [R]20D =-84.5 (c = 1.00, CHCl3); IR (KBr,
len-1-yl}carbamic acid tert-butyl ester (2f). Following the general cm-1) 3346(m), 3065(m), 2976 (m), 2926(m), 2803(w), 1707(s),
procedure (I), 2f was obtained as a yellow solid (20.7 mg, 25%): 1496(s), 1453(m), 1365(m), 1248(m), 1167(s), 1093(w), 1044(w),
Rf = 0.39 on silica gel (ethyl acetate/petroleum ether = 1:4, v/v); 1022(w), 934(w), 780(w), 741(m); 1H NMR (400 MHz, CDCl3) δ
mp 151-152 °C; ee was determined to be 61% using HPLC 7.34 (d, J = 7.2 Hz, 1H), 7.28-7.21 (m, 1H), 7.12 (d, J = 6.8 Hz,
analysis on a Chiralcel AD-H column (hexane/2-propanol = 90/ 1H), 7.05 (d, J = 7.2 Hz, 3H), 6.94 (d, J = 6.8 Hz, 1H), 6.68
10, 0.5 mL/min, λ = 254 nm); retention times were 30.4 min (d, J = 9.6 Hz,1H), 6.30 (dd, J = 12.8 Hz, 5.2 Hz, 1H), 5.10 (br s,
(minor) and 36.5 min (major); [R]20D = -124.3 (c = 1.00, CHCl3); 1H), 4.65 (dd, J = 10.0 Hz, 2.0 Hz, 1H), 3.90 (d, J=14.8 Hz, 1H),
IR (KBr, cm-1) 3353(m), 3065(w), 2976(w), 2920(w), 1686(s), 3.73 (d, J = 15.2 Hz, 1H), 3.60 (t, J =4.8 Hz, 1H), 2.87-2.80
1595(s), 1510(s), 1392(m), 1366(w), 1316(s), 1166(m), 1104(m), (m, 4H), 1.43 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 155.2,
1008(w), 938(w), 825(w), 784(m), 751(m), 616(w), 562(m); 1H 135.3, 135.2, 134.5, 132.4, 129.7, 128.7, 128.3, 128.1, 127.7, 126.8,
NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.6 Hz, 2H), 7.34 (d, 126.6, 125.8, 125.8, 125.4, 79.5, 63.5, 51.4, 48.5, 46.6, 29.9, 28.4;
J = 7.2 Hz, 1H), 7.29-7.22 (m, 1H), 7.13 (d, J = 6.8 Hz, 1H), MS (ESI) calcd m/z for C24H28N2O2 (Mþ) 376.22, found 399.03
6.81 (d, J = 7.6 Hz, 2H), 6.67 (d, J = 9.6 Hz, 1H), 5.85 (d, J = 10.0 (M þ Na)þ. Anal. Calcd for C24H28N2O2: C, 76.56; H, 7.50; N,
Hz, 1H), 5.17 (t, J = 9.6 Hz, 1H), 4.97 (d, J = 9.2 Hz, 1H), 4.62 7.44. Found: C, 76.69; H, 7.20; N, 7.63.

7296 J. Org. Chem. Vol. 75, No. 21, 2010

Long et al.
JOC Article
(1R,2R)-(2-Piperidin-1-yl-1,2-dihydronaphthalen-1-yl)carbamic (m, 2H), 7.16 (d, J = 7.2 Hz, 1H), 7.04 (d, J = 7.6 Hz, 2H), 6.67
acid tert-butyl ester (2j). Following the general procedure (I), 2j (d, J = 7.6 Hz, 2H), 6.57 (d, J = 9.2 Hz, 1H), 6.11 (dd, J = 4.4 Hz,
was obtained as a white solid (8.3 mg, 12%): Rf = 0.31 on silica 5.2 Hz, 1H), 5.08 (t, J = 7.2 Hz, 1H), 4.87 (d, J = 8.8 Hz, 1H), 4.27
gel (ethyl acetate/petroleum ether = 1:4, v/v); mp 115-118 °C; ee (s, 1H), 3.75 (s, 1H), 2.29 (s, 3H), 1.51 (s, 9H); 13C NMR (100 MHz,
was determined to be 19% using HPLC analysis on a Chiralcel CDCl3) δ 155.9, 145.8, 133.6, 132.3, 132.1, 128.9, 128.6, 128.4, 128.1,
OD-H column (hexane/2-propanol = 90/10, 0.5 mL/min, λ = 127.8, 127.0, 114.8, 109.1, 80.0, 53.4, 52.1, 28.4; MS (ESI) calcd m/z
254 nm); retention times were 7.4 min (major) and 7.7 min for C22H26N2O2 (Mþ) 350.45, found 373.27 (M þ Na)þ. Anal.
(minor); [R]20D = -44.9 (c = 1.00, CHCl3); IR (KBr, cm-1) Calcd for C22H26N2O2: C, 75.40; H, 7.48; N, 7.99. Found: C, 75.09;
3353(m), 2930 (s), 2854(w), 1714(s), 1494 (s), 1366(w), 1305(w), H, 7.88; N, 7.47.
1248(m), 1172(s), 745(m), 1119(w), 1045(w), 861(w), 779(w), General Procedure (II) for the Asymmetric Ring-Opening
745(w), 613(w); 1H NMR (400 MHz, CDCl3) δ 7.18-7.13 (m, Reactions of N-Boc-6,7-dimethoxy Azabenzonorbornadiene 3
2H), 7.02-6.99 (m, 1H), 6.56 (dd, J = 10.8 Hz, 8.8 Hz, 1H), 5.92 with Secondary Amine Nucleophiles. A 5 mL round-bottom flask
(dd, J = 14.4 Hz, 4.8 Hz, 1H), 4.96 (br s, 1H), 4.53 (br s, 1H), fitted with a reflux condenser was flame-dried under a stream
3.32-3.29 (m, 1H), 2.57-2.49 (m, 2H), 2.39-2.34 (m, 2H),1.45- of nitrogen and cooled to room temperature. [Ir(COD)Cl]2
1.41 (m, 4H), 1.38 (s, 9H), 1.33-1.27 (m, 2H); 13C NMR (100 (2.0 mg, 1.5 mol %) and (S)-BINAP (3.7 mg, 3 mol %) were
MHz, CDCl3) δ 155.1, 135.6, 132.4, 129.2, 128.1, 127.9, 127.7, simultaneously added and followed by the addition of anhy-
126.6, 126.1, 64.7, 49.9, 48.0, 29.7, 28.4, 26.4, 24.5; MS (ESI) calcd drous THF (2 mL). After the reaction mixture was stirred for
m/z for C20H28N2O2 (Mþ) 328.22, found 329.24 (M þ H)þ; Anal. 10 min at room temperature, N-Boc-6,7-dimethoxy azabenzo-
Calcd for C20H28N2O2: C, 73.14; H, 8.59; N, 8.53. Found: C, norbornadiene 3 (60 mg, 0.20 mmol) was added and the
73.49; H, 8.30; N, 8.23. temperature of the oil bath was increased to 80 °C. On the first
(1R,2R)-[2-(4-Phenylpiperazin-1-yl)-1,2-dihydronaphthalen-1-yl]- sign of reflux, nucleophile (3-5 equiv to 3) was added. The
carbamic acid tert-butyl ester (2k). Following the general procedure reaction was stirred at 80 °C until completion as monitored by
(I), 2k was obtained as a white solid (35.2 mg, 40%): Rf = 0.36 on thin layer chromatography. After the reaction mixture was
silica gel (ethyl acetate/petroleum ether = 1:4, v/v); mp 164- cooled to room temperature, the solvent was removed in vacuo
165 °C; ee was determined to be 37% using HPLC analysis on a and the residue was purified by column chromatography on
Chiralcel OD-H column (hexane/2-propanol = 90/10, 0.5 mL/min, silica gel (200-300 mesh) to give the desired product.
λ = 254 nm); retention times were 13.7 min (major) and 15.0 min (1R,2R)-[6,7-Dimethoxy-2-(methylphenylamino)-1,2-dihydro-
(minor); [R]20D = -80.2 (c = 1.00, CHCl3); IR (KBr, cm-1) naphthalen-1-yl]carbamic acid tert-butyl ester (4a). Following
3333(s), 3036(w), 2963(m), 2824(m), 1679(s), 1601(m), 1497(m), the general procedure (II), 4a was obtained as a white solid
1368(m), 1231(m), 1173(s), 758(m); 1H NMR (400 MHz, CDCl3) (45.1 mg, 55%): Rf = 0.37 on silica gel (ethyl acetate/petroleum
δ 7.35 (d, J = 7.6 Hz, 1H), 7.27-7.20 (m, 3H), 7.11-7.09 (m, 1H), ether = 1:4, v/v); mp 137-140 °C; ee was determined to be 83%
6.86 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 6.67 (d, J = 10.0 using HPLC analysis on a Chiralcel AD column (hexane/
Hz, 1H), 6.01 (dd, J = 7.2 Hz, 4.8 Hz, 1H), 5.06 (br s, 1H), 4.62 (br 2-propanol = 98/2, 1.0 mL/min, λ = 254 nm); retention times
d, J = 6.8 Hz, 1H), 3.48 (t, J = 4.4 Hz, 1H), 3.11 (t, J = 4.8 Hz, were 25.2 min (minor) and 28.1 min (major); [R]20D = -49.3
4H), 2.83-2.77 (m, 2H), 2.71-2.68 (m, 2H), 1.44 (s, 9H); 13C (c = 1.00, CHCl3); IR (KBr, cm-1) 3369(m), 3069(w), 2971(m),
NMR (100 MHz, CDCl3) δ 155.4, 151.6, 135.5, 132.6, 129.9, 129.2, 2972(m), 1717(s), 1595(m), 1506(s), 1385(m), 1278(m), 1161(m),
128.5, 128.3, 128.0, 126.9, 125.6, 119.7, 116.3, 79.7, 64.1, 49.8, 48.9, 1100(m), 944(m), 908(m), 866(m), 742(m), 575(m); 1H NMR
29.7, 28.4; MS (ESI) calcd m/z for C25H31N3O2 (Mþ) 405.24, found (400 MHz, CDCl3) δ 7.26-7.21 (m, 1H), 6.89 (d, J = 8.8 Hz,
406.12 (M þ H)þ. Anal. Calcd for C25H31N3O2: C, 74.04; H, 7.70; 3H), 6.73 (t, J = 7.2 Hz, 1H), 6.66 (s, 1H), 6.57 (dd, J = 1.6 Hz,
N, 10.36. Found: C, 74.09; H, 8.00; N, 10.47. 1.2 Hz, 1H), 5.84 (dd, J = 13.6 Hz, 6.0 Hz, 1H), 5.07 (t, J =
(1R,2R)-[2-(4-Bromophenylamino)-1,2-dihydronaphthalen-1-yl]- 8.8 Hz, 1H), 4.71 (d, J = 7.6 Hz, 1H), 4.55 (d, J = 8.4 Hz, 1H),
carbamic acid tert-butyl ester (2l). Following the general procedure 3.88 (s, 3H), 3.87 (s, 3H), 2.76 (s, 3H), 1.37 (s, 9H); 13C NMR
(I), 2l was obtained as a white solid (65.6 mg, 79%): Rf = 0.31 on (100 MHz, CDCl3) δ 155.3, 149.9, 148.6, 148.4, 129.7, 129.1,
silica gel (ethyl acetate/petroleum ether = 1:8, v/v); mp 93-95 °C; 128.3, 126.6, 125.4, 124.1, 117.1, 113.7, 110.3, 79.5, 60.2, 56.0,
ee was determined to be 83% using HPLC analysis on a Chiralcel 56.0, 52.0, 33.0, 28.2; MS (ESI) calcd m/z for C24H30N2O4 (Mþ)
AD-H column (hexane/2-propanol = 90/10, 0.5 mL/min, λ = 254 410.22, found 433.27 (M þ Na)þ. Anal. Calcd for C24H30N2O4:
nm); retention times were 16.6 min (major) and 31.2 min (minor); C, 70.22; H, 7.37; N, 6.82. Found: C, 70.60; H, 7.60; N, 6.79.
[R]20D = -132.1 (c = 1.00, CHCl3); IR (KBr, cm-1) 3398(w), (1R,2R)-[2-(Ethylphenylamino)-6,7-dimethoxy-1,2-dihydro-
2976(w), 1702(s), 1593(m), 1496(s), 1453(w), 1367(w), 1319(w), naphthalen-1-yl]carbamic acid tert-butyl ester (4b). Following the
1248(m), 1168(s), 814(m), 782(m); 1H NMR (400 MHz, CDCl3) general procedure (II), 4b was obtained as a white solid (38.2 mg,
δ 7.29-7.19 (m, 4H), 7.12 (d, J = 7.2 Hz, 1H), 6.58 (q, J = 7.2 Hz, 45%): Rf = 0.29 on silica gel (ethyl acetate/petroleum ether = 1:4,
3H), 6.03 (q, J = 5.2 Hz, 1H), 4.97 (t, J = 6.8 Hz, 1H), 4.68 (d, J = v/v); mp 130-135 °C; ee was determined to be 53% using HPLC
8.4 Hz, 1H), 4.21 (s 1H), 3.85 (s, 1H), 1.44 (s, 9H); 13C NMR (100 analysis on a Chiralcel AD column (hexane/2-propanol = 98/2,
MHz, CDCl3) δ 155.9, 145.8, 133.6, 132.3, 132.1, 128.9, 128.6, 1.0 mL/min, λ = 254 nm); retention times were 26.2 min (major)
128.4, 128.1, 127.8, 127.0, 114,8, 109.1, 80.0, 53.4, 52.1, 28.4; MS and 28.4 min (minor); [R]20D = -59.7 (c = 1.00, CHCl3); IR (KBr,
(ESI) calcd m/z for C21H23BrN2O2 (Mþ) 415.32, found 416.94 cm-1) 3347(w), 3046(w), 2971(w), 29279(w), 1709(s), 1062(m),
(M þ H)þ. Anal. Calcd for C21H23BrN2O2: C, 60.73; H, 5.58; N, 1502(s), 1371(w), 1256(s), 1159(s), 1085(m), 988(m), 840(m),
6.74. Found: C, 60.42; H, 5.72; N, 6.32. 746(m), 688(m), 515(m); 1H NMR (400 MHz, CDCl3) δ 7.24 (t,
(1R,2R)-[2-(p-Toluidino)-1,2-dihydronaphthalen-1-yl]carbamic J = 7.6 Hz, 1H), 6.89 (d, J = 7.2 Hz, 2H), 6.86 (s, 1H), 6.72 (t, J =
acid tert-butyl ester (2m). Following the general procedure (I), 2m 6.8 Hz, 1H), 6.66 (s, 1H), 6.57 (d, J = 9.6 Hz, 1H), 5.85 (dd, J =
was obtained as a white solid (40.6 mg, 58%): Rf = 0.38 on silica 12.8 Hz, 6.0 Hz, 1H), 5.01 (t, J = 8.2 Hz, 1H), 4.60 (br s, 1H), 3.89
gel (ethyl acetate/petroleum ether = 1:8, v/v); mp 80-82 °C; ee (s, 3H), 3.86 (s, 3H), 3.21 (q, 2H), 1.41 (s, 9H), 1.03 (t, J = 6.8 Hz,
was determined to be 86% using HPLC analysis on a Chiralcel 3H); 13C NMR (100 MHz, CDCl3) δ 155.3, 149.5, 148.6, 148.5,
OD column (hexane/2-propanol=90/10, 0.5 mL/min, λ=254 nm); 130.1, 129.2, 128.3, 126.2, 125.2, 124.1, 116.8, 114.0, 110.8, 80.5,
retention times were 10.1 min (major) and 12.3 min (minor); 59.5, 56.0, 56.0, 51.9, 39.9, 28.3, 14.1; MS (ESI) calcd m/z for
[R]20D = -24.5 (c = 1.00, CHCl3); IR (KBr, cm-1) 3386(w), C25H32N2O4 (Mþ) 424.24, found 447.26 (M þ Na)þ. Anal. Calcd
2976(w), 1706(s), 1616(w), 1519(s), 1366(w), 1299(w), 1245(w), for C25H32N2O4: C, 70.73; H, 7.60; N, 6.60. Found: C, 70.93; H,
1166(s), 808(m), 782(m); 1H NMR (400 MHz, CDCl3) δ 7.35-7.23 7.50; N, 6.43.

J. Org. Chem. Vol. 75, No. 21, 2010 7297

JOC Article Long et al.

(1R,2R)-[2-(3,4-Dihydro-2H-quinolin-1-yl)-6,7-dimethoxy-1,2- 1323(s), 1156(s), 1093(m), 1030(w), 919(w), 811(w), 1030(w),

dihydronaphthalen-1-yl]carbamic acid tert-butyl ester (4c). Fol- 747(m), 663(m), 546(m); 1H NMR (400 MHz, CDCl3) δ 7.61
lowing the general procedure (II), 4c was obtained as a white solid (d, J = 8.0 Hz, 2H), 7.25-7.16 (m, 5H), 7.11 (d, J = 7.6 Hz,
(50.6 mg, 58%): Rf = 0.3 on silica gel (ethyl acetate/petroleum 2H), 6.93 (d, J = 7.6 Hz, 1H), 6.75 (t, J = 7.8 Hz, 3H), 6.69
ether = 1:4, v/v); mp 140-145 °C; ee was determined to be 44% (dd, J = 10.8 Hz, 8.4 Hz, 1H), 5.85 (dd, J = 14.4 Hz, 4.8 Hz,
using HPLC analysis on a Chiralcel OD-H column (hexane/ 1H), 4.78 (d, J = 8.0 Hz, 1H), 4.70-4.67 (m, 1H), 4.57 (dd,
2-propanol = 90/10, 0.5 mL/min, λ = 254 nm); retention times J = 13.2 Hz, 2.0 Hz, 1H), 2.40 (s, 3H), 2.34 (s, 3H); 13C NMR
were 18.3 min (major) and 25.0 min (minor); [R]20D = -72.2 (c = (100 MHz, CDCl3) δ 148.9, 143.3, 137.6, 133.8, 132.2, 130.4,
1.00, CHCl3); IR (KBr, cm-1) 3363(m), 2971(m), 2932(m), 129.6, 129.1, 128.7, 128.4, 127.6, 127.2, 127.0, 126.1, 117.6,
2833(w), 1710(s), 1600(m), 1504(s), 1455(m), 1390(w), 1366(w), 113.9, 59.1, 54.6, 32.4, 21.6; MS (ESI) calcd m/z for C24H24-
1274(m), 1227(w), 1160(m), 1108(w), 1015(w), 867(w), 742(m), N2O2S (Mþ) 404.16, found 427.30 (M þ Na)þ. Anal. Calcd for
604(w); 1H NMR (400 MHz, CDCl3) δ 6.96 (d, J = 7.2 Hz, 1H), C24H24N2O2S: C, 71.26; H, 5.98; N, 6.93. Found: C, 71.29; H,
6.87 (t, J = 8.6 Hz, 2H), 6.66 (s, 1H), 6.61-6.55 (m, 2H), 5.82 (dd, 6.28; N, 6.78.
J = 12.8 Hz, 6.0 Hz, 1H), 5.12 (q, 1H), 4.72 (dd, J = 36.0 Hz, 21.2 (1R,2R)-N-[2-(Ethylphenylamino)-1,2-dihydronaphthalen-1-yl]-
Hz, 2H), 3.88 (s, 3H), 3.87 (s, 3H),3.22-3.17 (m, 1H), 3.07 (s, 4-methylbenzenesulfonamide (6b). Following the general proce-
1H), 2.72 (t, J = 6.4 Hz, 2H), 1.87-1.78 (m, 2H), 1.38 (s, 9H); 13C dure (III), 6b was obtained as a white solid (66.8 mg, 79%): Rf =
NMR (100 MHz, CDCl3) δ 155.4, 148.5, 148.4, 145.2, 129.8, 0.35 on silica gel (ethyl acetate/petroleum ether = 1:4, v/v); mp
129.5, 128.5, 127.0, 126.2, 125.5, 123.7, 116.1, 111.3, 110.3, 110.2, 134-135 °C; ee was determined to be 80% using HPLC anal-
79.5, 57.9, 56.0, 56.0, 51.4, 43.3, 28.3, 28.2, 22.4; MS (ESI) calcd ysis on a Chiralcel OD-H column (hexane/2-propanol = 90/10,
m/z for C26H32N2O4 (Mþ) 436.24, found 459.35 (M þ Na)þ. 0.5 mL/min, λ = 254 nm); retention times were 10.6 min (major)
Anal. Calcd for C26H32N2O4: C, 71.53; H, 7.39; N, 6.42. Found: and 13.1 min (minor); [R]20D = -119.8 (c = 1.00, CHCl3); IR
C, 71.22; H, 7.60; N, 6.49. (KBr, cm-1) 3268(m), 3053(w), 2956(w), 2924(m), 1595(s), 1501(s),
(1R,2R)-[6,7-Dimethoxy-2-(4-phenylpiperazin-1-yl)-1,2-dihy- 1323(m), 1262(m), 1156(s), 1092(w), 914(m), 813(m), 748(m),
dronaphthalen-1-yl]carbamic acid tert-butyl ester (4d). Following 663(m), 564(m); 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.4
the general procedure (II), 4d was obtained as a white solid Hz, 2H), 7.16-7.09 (m, 5H), 7.04 (dd, J = 8.4 Hz, 6.4 Hz, 1H), 6.96
(29.8 mg, 32%): Rf = 0.29 on silica gel (ethyl acetate/petroleum (ddd, J = 16.4 Hz, 14.0 Hz, 1.2 Hz, 1H), 6.70 (d, J = 8.4 Hz, 2H),
ether = 1:3, v/v); mp 184-185 °C; ee was determined to be 56% 6.66 (t, J = 3.6 Hz, 2H), 6.63 (d, J = 1.2 Hz, 1H), 5.88 (dd, J = 14.8
using HPLC analysis on a Chiralcel OD-H column (hexane/ Hz, 4.4 Hz, 1H), 4.73 (d, J = 8.0 Hz, 1H), 4.51-4.49 (m, 1H), 4.46
2-propanol = 90/10, 0.5 mL/min, λ = 254 nm); retention times (dd, J = 11.6 Hz, 4.4 Hz, 1H), 2.85 (q, 2H), 2.33 (s, 3H), 0.71 (t, J =
were 19.0 min (minor) and 25.9 min (major); [R]20D = -37.1 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 146.8, 143.3, 137.7,
(c = 1.00, CHCl3); IR (KBr, cm-1) 3347(m), 2928(m), 2826(w), 133.5, 132.2, 130.4, 129.6, 129.2, 128.8, 128.4, 128.2, 127.3, 127.1,
1702(s), 1599(s), 1501(s), 1446(m), 1309(w), 1232(s), 1164(m), 126.1, 116.9, 113.8, 58.2, 54.1, 39.8, 21.6, 14.1; MS (ESI) m/z calcd
993(m), 758(m), 593(m), 605(w); 1H NMR (400 MHz, CDCl3) for C25H26N2O2S (Mþ) 418.17, found 441.23 (M þ Na)þ. Anal.
δ 7.24-7.18 (m, 2H), 6.84 (d, J = 8.4 Hz, 3H), 6.80 (t, J = 7.4 Hz, Calcd for C25H26N2O2S: C, 71.74; H, 6.26; N, 6.69. Found: C, 71.51;
1H), 6.62 (s, 1H), 6.58 (d, J = 10.0 Hz, 1H), 5.85 (dd, J = 14.4 H, 6.48; N, 6.91.
Hz, 4.4 Hz, 1H), 4.94 (br s, 1H), 4.58 (br s, 1H), 3.87 (s, 3H), 3.86 (1R,2R)-N-[2-(Methyl-m-tolylamino)-1,2-dihydronaphthalen-
(s, 3H), 3.41 (s, 1 H), 3.08 (d, J = 4.4 Hz, 4H), 2.79 (t, J = 10.8 1-yl]-4-methylbenzenesulfonamide (6c). Following the general
Hz, 2H), 2.62 (t, J = 10.4 Hz, 2H), 1.43 (s, 9H); 13C NMR (100 procedure (III), 6c was obtained as a white solid (73.6 mg,
MHz, CDCl3) δ 155.1, 151.4, 148.8, 148.6, 129.3, 129.0, 127.6, 88%): Rf = 0.20 on silica gel (ethyl acetate/petroleum ether =
125.1, 122.9, 119.5, 116.0, 111.4, 110.0, 79.5, 63.5, 56.1, 56.0, 49.6, 1:6, v/v); mp 120-124 °C; ee was determined to be 86%
48.6, 47.9, 28.4; MS (ESI) calcd m/z for C27H35N3O4 (Mþ) using HPLC analysis on a Chiralcel AD column (hexane/
465.26, found 466.18 (M þ H)þ. Anal. Calcd for C27H35N3O4: 2-propanol = 90/10, 1.0 mL/min, λ = 254 nm); retention times
C, 69.65; H, 7.58; N, 9.03. Found: C, 69.99; H, 7.22; N, 9.40. were 12.2 min (minor) and 14.0 min (major)l [R]20D = -93.4
General Procedure (III) for the Asymmetric Ring-Opening (c = 1.00, CHCl3); IR (KBr, cm-1) 3271(m), 3028(w), 2917(w),
Reactions of N-Ts-Azabenzonorbornadiene 5 with Secondary 1598(s), 1494(s), 1450(m), 1323(s), 1302(s), 1155(s), 1092(m),
Amine Nucleophiles. A 5 mL round-bottom flask fitted with a 1081(w), 949(w), 782(m), 664(s), 616(w), 564(s); 1H NMR (400
reflux condenser was flame-dried under a stream of nitrogen and MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 2H), 7.16 (t, J = 7.4 Hz,
cooled to room temperature. [Ir(COD)Cl]2 (2.0 mg, 1.5 mol %) 1H), 7.11 (d, J = 8.2 Hz, 2H), 7.02 (t, J = 7.8 Hz, 3H), 6.83 (d,
and (S)-BINAP (3.7 mg, 3 mol %) were simultaneously added J = 6.8 Hz, 1H), 6.60 (d, J = 9.6 Hz, 1H), 6.56 (s, 1H), 6.52 (d,
and followed by the addition of anhydrous THF (2 mL). After J = 7.6 Hz, 1H), 6.50 (dd, J = 10.8 Hz, 6.0 Hz, 1H), 5.79 (dd,
the reaction mixture was stirred for 10 min at room temperature, J = 14.4 Hz, 4.8 Hz, 1H), 4.64-4.61 (m, 1H), 4.58-4.49 (m,
N-Ts-azabenzonorbornadiene 5 (60 mg, 0.20 mmol) was added 2H), 2.37 (s, 3H), 2.26 (s, 3H), 2.25 (s, 3H); 13C NMR (100 MHz,
and the temperature of the oil bath was increased to 100 °C. On CDCl3) δ 149.0, 143.2, 138.9, 137.6, 133.8, 132.3, 130.3, 129.5,
the first sign of reflux, nucleophile (3-5 equiv to 5) was added. 129.0, 128.7, 128.3, 127.7, 127.2, 127.0, 126.2, 118.6, 114.7,
The reaction was stirred at 100 °C until completion as monitored 111.1, 59.0, 54.6, 32.4, 21.8, 21.5; MS (ESI) calcd m/z for
by thin layer chromatography. After the reaction mixture was C25H26N2O2S (Mþ) 418.17, found 441.20 (M þ Na)þ. Anal.
cooled to room temperature, the solvent was removed in vacuo Calcd for C25H26N2O2S: C, 71.74; H, 6.26; N, 6.69. Found: C,
and the residue was purified by column chromatography on 71.50; H, 6.50; N, 6.91.
silica gel (200-300 mesh) to give the desired product. (1R,2R)-N-[2-(p-Toluidino)-1,2-dihydronaphthalen-1-yl]-4-methyl-
(1R,2R)-4-Methyl-N-[2-(methylphenylamino)-1,2-dihydro- benzenesulfonamide (6e). Following the general procedure
naphthalen-1-yl]-benzenesulfonamide (6a). Following the general (III), 6e was obtained as a white solid (77.6 mg, 96%): Rf =
procedure (III), 6a was obtained as a white solid (74.3 mg, 92%): 0.25 on silica gel (ethyl acetate/petroleum ether = 1:4, v/v); mp
Rf = 0.36 on silica gel (ethyl acetate/petroleum ether = 1:4, v/v); 56-58 °C; ee was determined to be 94% using HPLC analysis
mp 130-132 °C; ee was determined to be 70% using HPLC analysis on a Chiralcel OD-H column (hexane/2-propanol = 90/10,
on a Chiralcel OD-H column (hexane/2-propanol = 90/10, 0.5 mL/ 0.5 mL/min, λ = 254 nm); retention times were 27.3 min (major)
min, λ = 254 nm); retention times were 23.0 min (minor) and and 34.9 min (minor); [R]20D = -91.1 (c = 1.00, CHCl3); IR
29.6 min (major); [R]20D = -102.6 (c = 1.00, CHCl3); IR (KBr, (KBr, cm-1) 3277(w), 3026(w), 2920(w), 1615(m), 1518(s),
cm-1) 3277(m), 3063(w), 2925(w), 1596(s), 1503(s), 1451(w), 1407(w), 1328(s), 1158(s), 1093(m), 1041(w), 922(w), 811(m),

7298 J. Org. Chem. Vol. 75, No. 21, 2010

Long et al.
JOC Article
762(w), 664(m), 565(m), 547(m); 1H NMR (400 MHz, CDCl3) 1043(m), 923(w), 796(m), 665(m), 567(m), 548(m); 1H NMR
δ 7.71 (dd, J = 2.0 Hz, 6.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), (400 MHz, CDCl3) δ 7.73 (d, J = 8.4 Hz, 2H), 7.28 (d, J =
7.21 (t, J = 6.8 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 7.01 (d, J = 8.0 Hz, 2H), 7.21 (t, J = 7.2 Hz, 1H), 7.09 (d, J = 7.2 Hz, 1H),
7.2 Hz, 1H), 6.96 (d, J = 8.4 Hz, 2H), 6.60 (d, J = 7.6 Hz, 1H), 7.02-6.96 (m, 3H), 6.57 (t, J = 6.8 Hz, 2H), 6.51 (d, J = 8.0 Hz,
6.55 (d, J = 9.6 Hz, 1H), 6.48 (dd, J = 2.0 Hz, 6.4 Hz, 2H), 2H), 6.04 (q, J = 4.0 Hz, 1H), 4.91 (t, J = 8.0 Hz, 1H), 4.44 (dd,
6.05-6.01 (m, 1H), 5.13 (d, J = 7.6 Hz, 1H), 4.46-4.44 (m, J = 3.2 Hz, 4.4 Hz, 1H), 4.30 (t, J = 4.8 Hz, 1H), 3.35 (s, 1H),
1H), 4.28 (s, 1H), 3.26 (s, 1H), 2.44 (s, 3H), 2.25 (s, 3H); 13C 2.47 (q, J = 8.0 Hz, 4H), 1.64-1.55 (m, 2H), 1.26 (s, 1H), 0.94 (t,
NMR (100 MHz, CDCl3) δ 140.9, 134.9, 129.5, 129.3, 127.3, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 143.7, 143.5,
127.2, 126.6, 126.4, 125.7, 124.8, 124.6, 124.4, 124.2, 110.9, 137.5, 132.1, 131.8, 129.8, 129.3, 129.2, 129.0, 128.9, 128.3,
50.9, 49.8, 19.0, 17.9; MS (ESI) calcd m/z for C24H24N2O2S 127.4, 127.2, 126.8, 113.3, 53.5, 52.4, 37.2, 24.9, 21.6, 13.9; MS
(Mþ) 404.52, found 427.38 (M þ Na)þ. Anal. Calcd for (ESI) calcd m/z for C26H28N2O2S (Mþ) 432.58, found 455.36
C24H24N2O2S: C, 71.26; H, 5.98; N, 6.93. Found: C, 71.65; (M þ Na)þ. Anal. Calcd for C26H28N2O2S: C, 72.19; H, 6.52; N,
H, 6.35; N, 6.60. 6.48. Found: C, 72.45; H, 6.89; N, 6.87.
(1R,2R)-N-[2-(2,4-Dimethoxyphenylamino)-1,2-dihydronaphtha- (1R,2R)-N-[2-(4-Bromophenylamino)-1,2-dihydronaphthalen-
len-1-yl]-4-methylbenzenesulfonamide (6f). Following the general 1-yl]-4-methylbenzenesulfonamide (6h). Following the general
procedure (III), 6f was obtained as a white solid (52.2 mg, 58%): procedure (III), 6h was obtained as a white solid (78.8 mg,
Rf = 0.26 on silica gel (ethyl acetate/petroleum ether = 1:4, v/v); 84%): Rf = 0.15 on silica gel (ethyl acetate/petroleum ether =
mp 140-142 °C; ee was determined to be 97% using HPLC analysis 1:6, v/v); mp 165-167 °C; ee was determined to be 22% using
on a Chiralcel AD-H column (hexane/2-propanol = 90/10, 0.5 mL/ HPLC analysis on a Chiralcel AD-H column (hexane/2-propa-
min, λ = 254 nm); retention times were 102.3 min (major) and 116.0 nol = 90/10, 0.5 mL/min, λ = 254 nm); retention times were
min (minor); [R]20D = -108.4 (c = 1.00, CHCl3); IR (KBr, cm-1) 67.2 min (major) and 88.5 min (minor); [R]20D = -51.6 (c =
3258(w), 2924 (m), 1596(w), 1514(s), 1453(m), 1416(m), 1497(m), 1.00, CHCl3); IR (KBr, cm-1) 3276(w), 3028(w), 2848(w),
1289(m), 1205(m), 1156(s), 1093(w), 1032(m), 796(m), 664(m), 1592(s), 1493(s), 1402(m), 1317(s), 1156(s), 1092(m), 812 (s),
566(m); 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.0 Hz, 663(m), 571(m), 547(m); 1H NMR (400 MHz, CDCl3) δ 7.73 (d,
2H), 7.28 (d, J = 8.0 Hz, 2H), 7.22 (t, J = 6.4 Hz, 1H), 7.10 (d, J = J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.15 (t, J = 8.0 Hz,
7.6 Hz, 1H), 7.00 (t, J = 7.2 Hz, 1H), 6.81 (d, J = 8.4 Hz, 1H), 6.59 2H), 7.10 (d, J = 7.6 Hz, 1H), 7.01 (t, J = 7.2 Hz, 1H), 6.71 (t,
(d, J = 9.6 Hz, 1H), 6.54 (d, J = 7.2 Hz, 1H), 6.46 (dd, J = 2.4 Hz, J = 7.6 Hz, 1H), 6.59-6.56 (m, 4H), 6.05 (q, J = 4.0 Hz, 1H),
6.0 Hz, 1H), 6.38 (d, J = 2.4 Hz, 1H), 6.08 (q, J = 4.0 Hz, 1H), 4.95 4.87 (d, J = 7.6 Hz, 1H), 4.45 (dd, J = 3.6 Hz, 4.4 Hz, 1H), 4.33
(s, 1H), 4.47 (dd, J = 2.4 Hz, 5.2 Hz, 1H), 4.28 (q, J = 2.4 Hz, 1H), (t, J = 4.0 Hz, 1H), 3.46 (s, 1H), 2.44 (s, 3H); 13C NMR (100
3.78 (s, 3H), 3.63 (s, 3H), 2.45 (s, 3H), 1.28 (s, 1H); 13C NMR MHz, CDCl3) δ 144.9, 143.7, 137.3, 132.1, 131.8, 131.7, 129.8,
(100 MHz, CDCl3) δ 149.6, 145.5, 140.9, 134.9, 129.5, 129.2, 127.2, 129.3, 129.2, 129.0, 128.5, 127.3, 126.2, 114.9, 109.4, 53.3, 52.3,
127.1, 126.7, 126.3, 125.6, 124.8, 124.6, 124.1, 108.6, 101.3, 96.7, 21.6; MS (ESI) calcd m/z for C23H21BrN2O2S (Mþ) 469.39,
53.2, 52.7, 50.8, 50.2, 19.0; MS (ESI) calcd m/z for C25H26N2O4S found 491.30 (M þ Na)þ. Anal. Calcd for C23H21BrN2O2S: C,
(Mþ) 450.55, found 473.30 (M þ Na)þ. Anal. Calcd for C25H26- 58.85; H, 4.51; N, 5.97. Found: C, 58.49; H, 4.90; N, 6.25.
N2O4S: C, 66.64; H, 5.82; N, 6.22. Found: C, 66.34; H, 6.12; N, 6.62.
(1R,2R)-N-[2-(4-Propylphenylamino)-1,2-dihydronaphthalen- Acknowledgment. We are grateful to the National Natural
1-yl]-4-methylbenzenesulfonamide (6g). Following the general Science Foundation of China (Nos. 20772036 and 20802021)
procedure (III), 6g was obtained as colorless oil (48.4 mg, 56%): and the Natural Science Foundation of Guangdong Province
Rf = 0.15 on silica gel (ethyl acetate/petroleum ether = 1:6,
(Nos. 8251063101000002 and 7005804) for financial support.
v/v); ee was determined to be 94% using HPLC analysis on a
Chiralcel AD-H column (hexane/2-propanol = 90/10, 0.5 mL/
min, λ = 254 nm); retention times were 40.9 min (major) and Supporting Information Available: Copies of 1H and 13
C
43.9 min (minor); [R]20D = -116.4 (c = 1.00, CHCl3); IR (KBr, NMR spectra of compounds 2a-2m, 4a-4d, and 6a-6h, and
cm-1) 3394(w), 3276(m), 3037 (w), 2957(m), 2927(m), 2870(w), X-ray structure data for compound 2g. This material is available
1615 (m), 1518(s), 1454(w), 1412(m), 1329(m), 1160(s), 1094(m), free of charge via the Internet at http://pubs.acs.org.

J. Org. Chem. Vol. 75, No. 21, 2010 7299