Highly efficient Ir-catalyzed asymmetric hydrogenation of benzoxazinones and derivatives with a Bronsted acid cocatalyst

The Ir-catalyzed highly efficient asymmetric hydrogenation of benzoxazinones and derivatives was successfully developed with N-methylated ZhaoPhos L5 as the ligand, which may display a new activation mode with a single anion-binding interaction among the substrate, cocatalyst BrOnsted acid and ligand. This synthetic approach afforded a series of chiral dihydrobenzoxazinones and derivatives with excellent results (>99% conversion, 88-96% yields, 91->99% ee, up to 40500 TON). A key to success is the utilization of a strong BrOnsted acid as the cocatalyst, such as hydrochloric acid, to form a possible single anion-binding interaction with the substrate and catalyst, which greatly contributed to the improvement of reactivity and enantioselectivity. Importantly, a creative and efficient synthetic route was developed to construct the important intermediate for the potential IgE/IgG receptor modulator through our catalytic methodology system.