Atropisomeric compounds due to rotational restriction around an N-C bond have received much attention recently as novel chiral molecules. However, catalytic enantioselective synthesis of such N-C axially chiral compounds has not so far been reported. We succeeded in the highly enantioselective syntheses of atropisomeric ortho-tert-butyl anilides, lactams and indoles having an N-C chiral axis through chiral palladium-catalyzed N-C bond forming reactions. That is, in the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, N-arylation (Buchwald-Hartwig amination) of achiral ortho-tert-butylanilides with p-iodonitrobenzene proceeded in a highly enantioselective manner (88-96% ee) to give atropisomeric N-(p-nitrophenyl)anilides in good yields. The application of the present catalytic enantioselective N-arylation to an intramolecular version gave atropisomeric lactam derivatives with high optical purity (92 -98%ee). The a-alkylation with the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides proceeded with high diastereoselectivity (diastereomer ratio = 31 : 1-80 : 1). On the other hand, 5-endo-hydroaminocyclization of achiral ortho-alkynylanilines using (R)-SEGPHOS-PdCl2 catalyst afforded optically active atropisomeric indole derivatives (up to 83% ee) in good yields.
|ジャーナル||Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry|
|出版ステータス||Published - 2011 9|
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