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

Abstract 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.