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
-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
-arylation (Buchwald-Hartwig amination) of achiral ortho
-butylanilides with p
-iodonitrobenzene proceeded in a highly enantioselective manner (88−96% ee) to give atropisomeric N
-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 α-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
catalyst afforded optically active atropisomeric indole derivatives (up to 83% ee) in good yields.