Asymmetric Cyclopropanation of Primary N-Vinylamides via Carbene Transfer Catalyzed by Cationic Rh(I)/Diene Complexes: An Unexpected Outer-Sphere Mechanism

A highly enantioselective intermolecular [2 + 1] cycloaddition of primary N-vinylamides with carbene intermediates was developed by taking advantage of cationic rhodium(I)/diene catalysis under mild conditions at room temperature. This cyclopropanation method facilitates rapid access to enantioenriched cyclopropylamides, an important motif in drug discovery, in generally good yields and high stereoselectivities (>20:1 dr, up to 99% ee). This approach employs a cationic rhodium(I) catalyst to form a pre-equilibrium complex with an enamide substrate. Kinetic experiments and comprehensive density functional theory (DFT) calculations were performed to elucidate the reaction mechanism. The kinetic data and DFT results support the existence of a resting-state complex between the rhodium(I)/diene catalyst and two enamide substrates. The computational studies show that the reaction involves an interesting, unexpected outer-sphere mechanistic pathway involving a sole Rh(I) catalytic cycle to form the major product and reveal that the diazo decomposition step is the rate-determining step.