Catalytic Atroposelective Dynamic Kinetic Resolution of Substituted Indoles

Advances in asymmetric catalysis have led to enormous progress in the atroposelective synthesis of axially chiral biaryls. Because of the biological importance of indoles, stereogenic axes in aryl-substituted indoles have attracted considerable research attention in recent years. Here we present a summary of recent advances in the atroposelective synthesis of aryl-substituted indoles by dynamic kinetic resolution. While several researchers have developed enantioselective syntheses of 3-arylindoles, N-arylindoles have been much less studied. Accordingly, we have reported a Pictet–Spengler reaction with catalytic and enantioselective control of the axial chirality around the C−N bond of the product. A chiral phosphoric acid induces the cyclization smoothly and with high yields and excellent enantioselectivities. To achieve this high selectivity, an NH group at the ortho position of the N-substituted aromatic ring that interacts favorably with the catalyst is required. Furthermore, when substituted aldehydes are used instead of paraformaldehyde, both the point and axial chiralities can be controlled during the cyclization.