Copper‐Catalyzed Asymmetric Hydrogenation of Unsymmetrical <i>ortho</i> ‐Br Substituted Benzophenones

The asymmetric hydrogenation of benzophenones, catalyzed by low-activity earth-abundant metal copper, has hitherto remained a challenge due to the substrates equipped with two indistinguishably similar aryl groups. In this study, we demonstrated that the prochiral carbon of the ortho-bromine substrate exhibits the highest electrophilicity and high reactivity among the ortho-halogen substituted benzophenones, as determined by the Fukui function (f⁺) analysis and hydrogenation reaction. Considering that the enantiodirecting functional bromine group can be easily derivatized and removed in the products, we successfully achieved a green copper-catalyzed asymmetric hydrogenation of ortho-bromine substituted benzophenones. This method yielded a series of chiral benzhydrols with excellent results. The utility of this protocol has been validated through a gram-scale reaction and subsequent product transformations. Independent gradient model based on Hirshfeld partition (IGMH) and energy decomposition analysis (EDA) indicate that the CH⋅⋅⋅HC multiple attractive dispersion interactions (MADI) effect between the catalyst and substrate enhances the catalyst's activity.