ORGANIC LETTERS
Stereoselective Synthesis of Axially Chiral N−C Bonds in N-Aryl Indoles
2006 Vol. 8, No. 6 1097-1100
Ken Kamikawa,*,† Shunsuke Kinoshita,† Hiroyuki Matsuzaka,† and Motokazu Uemura*,§ Department of Chemistry, Graduate School of Science, Osaka Prefecture UniVersity, Sakai, Osaka 599-8531, Japan, and Kyoto Pharmaceutical UniVersity, Misasagi, Yamashina, Kyoto 640-8412, Japan
[email protected];
[email protected] Received December 12, 2005
ABSTRACT
N-Aryl indoles with axially chiral N−C bonds were synthesized by stereoselective nucleophilic aromatic substitution reactions of planar chiral arene chromium complexes. Stereoselective chromium tricarbonyl migration was achieved in the sterically hindered N-aryl indole chromium complex by refluxing in toluene.
o-Substituted anilides, N-aryl indoles, carbazoles, and related compounds possessing the chiral N-C bond have received much attention as novel atropisomeric compounds. As these axially chiral compounds are expected to be useful for asymmetric reactions and as molecular devices, their stereoselective syntheses have been the focus of recent studies.1 The asymmetric synthesis of axially chiral anilides has been reported by several groups. Simpkins2 and our group3 reported the asymmetric desymmetrization of the ortho substituents in prochiral anilides with a stoichiometric amount of a chiral base. Recently, Taguchi4 and Curran5 developed the catalytic asymmetric synthesis of atropisomeric anilides by N-arylation or allylation reactions. On the other hand, †
Osaka Prefecture University. Kyoto Pharmaceutical University. (1) (a) Curran, D. P.; Qi, H.; Geib, S. J.; DeMello, N. C. J. Am. Chem. Soc. 1994, 116, 3131. (b) Tetrahedron Symposium in-print on Axially Chiral Amide; Clayden, J. Ed.; Tetrahedron 2004, 60, 4325. (2) Bennett, D. J.; Pickering, P. L.; Simpkins, N. S. Chem. Commun. 2004, 1392. (3) (a) Hata, T.; Koide, H.; Taniguchi, N.; Uemura, M. Org. Lett. 2000, 2, 1907. (b) Koide, H.; Hata, T.; Uemura, M. J. Org. Chem. 2002, 67, 1929. §
10.1021/ol0529997 CCC: $33.50 Published on Web 02/15/2006
© 2006 American Chemical Society
the asymmetric synthesis of N-arylamines, including N-aryl indoles and carbazoles with axial chirality, has not been reported so far, although they have been receiving increasing attention for use as chiral ligands6 and in such natural products as murrastifoline-F.7 There is also no report on the stereoselective N-C bond formation of these axially chiral species. Recently, the palladium-catalyzed reaction involving N-C(aryl) bond formation has been actively studied and widely recognized as a useful method.8 Another promising approach for the formation of N-C bonds is the aromatic nucleophilic substitution reaction of activated arenes;9 however, this stereoselective reaction has not been successfully (4) (a) Kitagawa, O.; Takashi, M.; Yoshikawa, M.; Taguchi, T. J. Am. Chem. Soc. 2005, 127, 3676. (b) Kitagawa, O.; Kohriyama, M.; Taguchi, T. J. Org. Chem. 2002, 67, 8682. (5) Terauchi, J.; Curran, D. P. Tetrahedron: Asymmetry 2003, 14, 587. (6) Mino, T.; Tanaka, Y.; Sakamoto, M.; Fujita, T. Tetrahedron: Asymmetry 2001, 12, 2435. (7) Bringmann, G.; Tasler, S.; Endress, H.; Kraus, J.; Messer, K.; Wohlfarth, M.; Lobin, W. J. Am. Chem. Soc. 2001, 123, 2703. (8) (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 852. (b) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 805.
Table 1. Stereoselective Nucleophilic Substitution Reaction for the Synthesis of Axially Chiral N-Aryl Indole Chromium Complexes
Figure 1. X-ray structure of complex 3aa.
entry
indole
complex
product
yield (%) 3 or 4
ratio 3:4
1 2 3 4 5 6 7 8
1a 1a 1b 1c 1d 1e 1f 1f
2a 2b 2a 2a 2a 2a 2a 2b
3aa 3ab 4ba 4ca 3da 3ea 3fa 3fb
76 76 50 83 77 70 86 65
>98:98:98:98:98:98:
