Carbene-catalytic enantioselective synthesis of chiral macrocycles.

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.