Rh-Catalyzed Expansion of Azetidines to Pyrrolidines via Modulated Carbene Transfer

Abstract Reliable methods for accessing complex pyrrolidines without the need for extensive pre-functionalization or harsh reaction conditions are attractive. We report a Rh-catalyzed ring-expansion strategy, in which azetidines react with donor–acceptor carbene precursors to form azetidinium ylides that selectively rearrange to pyrrolidines. The protocol is operationally simple, proceeds under mild conditions, avoids slow addition of the carbene precursor, exhibits good functional group tolerance, and enables easy removal of the N-aryl group if desired. The resulting functional-group-rich N-aryl pyrrolidines are versatile intermediates for the efficient construction of complex, drug-like pyrrolidines. UV–Vis studies elucidate a key catalyst–substrate binding equilibrium dependent on the N-protecting group, providing mechanistic insight into the reaction’s unique behavior and informing future method development.