Revisiting the Stereodetermining Step in Enantioselective Iridium-Catalyzed Imine Hydrogenation

The mechanism for the iridium-catalyzed asymmetric hydrogenation of prochiral imines has been investigated for an experimentally relevant ligand–substrate combination using DFT calculations. The possible stereoisomers of the stereodetermining hydride transfer transition state were considered for four possible hydrogenation mechanisms starting from the recently disclosed active catalyst consisting of iridium phosphine-oxazoline with cyclometalated imine substrate. The hydrogenation was found to proceed via an outer-sphere pathway. The transition state accurately describes the experimental observations of the active catalyst and provides a structural rationale for the high stereoinduction despite the lack of direct interaction points in the outer-sphere mechanism. The predicted enantioselectivity was consistent with experimental observations. Experimental studies support the hypothesis that the iridacycle forms spontaneously and functions as the active catalyst in the hydrogenation.