Cascade asymmetric dearomative cyclization reactions via transition-metal-catalysis

Catalytic asymmetric dearomatization (CADA) reactions offer an efficient strategy for directly converting aromatic compounds into chiral cyclic molecules. Cascade dearomative cyclization reactions are an important subclass of these transformations, providing rapid access to various polycyclic scaffolds. Given the wide existence of natural products and bioactive molecules with polyheterocyclic skeletons, cascade dearomative cyclization reactions of versatile heteroaromatic compounds are particularly attractive. In this Review, we discuss representative examples of cascade asymmetric dearomative cyclization reactions catalysed by transition-metal complexes (including Au, Ir, Pd, Cu, Rh, Ni, Zn, Ti and V complexes) from the past decade. Close attention is paid to the dearomative cyclization reactions of indoles and related heteroaromatic compounds, with an emphasis on the reaction mechanisms, substrate scope and applications in total synthesis, as well as limitations and possible future directions.