Highly Enantioselective Synthesis of Atropisomeric Anilide Derivatives through Catalytic Asymmetric N-Arylation: Conformational Analysis and Application to Asymmetric Enolate Chemistry

In the presence of (R)-DTBM-SEGPHOS−Pd(OAc)2 catalyst, N-arylation (aromatic amination)
of various o-tert-butylanilides with p-iodonitrobenzene proceeds with high enantioselectivity (88−96% ee)
to give atropisomeric N-(p-nitrophenyl)anilides having an N−C chiral axis in good yields. Atropisomeric
anilide products highly prefer to exist as the E-rotamer which has trans-disposed o-tert-butylphenyl group
and carbonyl oxygen. The application of the present catalytic enantioselective N-arylation to an intramolecular
version gives atropisomeric lactam derivatives with high optical purity (92−98% ee). The reaction of the
lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides gives
α-alkylated products with high diastereoselectivity (diastereomer ratio = 13:1 to 46:1).