Abstract
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. Although several
researchers have developed enantioselective syntheses of 3-arylindoles, N-arylindoles have been much less studied. Accordingly, we have developed 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 point and axial chiralities can be controlled during the cyclization.
1 Introduction
2 Atropisomerism in Indoles
3 Atroposelective Dynamic Kinetic Resolution of 3-Arylindoles
4 Atroposelective Dynamic Kinetic Resolution of N-Arylindoles
5 Conclusions
Key words
arylindoles - atropisomerism - chiral phosphoric acids - dynamic kinetic resolution
- Pictet–Spengler cyclization
