Carbene-catalytic enantioselective synthesis of chiral macrocycles

Abstract

Chiral macrocyclic units are not only prevalent in natural products, bioactive molecules, and functional compounds, but also play significant roles in synthetic and host–guest chemistry. Although extensive efforts have been devoted to constructing chiral macrocycles, few methods have been disclosed to date. Consequently, the rapid enantioselective construction of optically active macrocycles remains a formidable challenge. N-Heterocyclic carbene (NHC) catalysis, a highly successful organocatalytic approach, has emerged as a powerful tool for rapidly constructing complex molecular architectures. However, only recently has this strategy been applied to achieve enantioselective synthesis of chiral macrocycles. This review highlights recent advances in NHC-catalyzed enantioselective synthesis of chiral macrocycles—including centrally chiral, planar chiral, and inherently chiral macrocycles, thereby providing a timely overview and foundation for future research.