Development and Scale-Up of a Direct Asymmetric Reductive Amination with Ammonia

Direct asymmetric reductive amination represents an efficient means of converting ketones to alpha-chiral primary amines, but reported examples are very limited. We describe the development of two sets of Ru-catalyzed conditions for the direct conversion of an aryl methyl ketone to a pharmaceutically relevant chiral primary amine. In the presence of NH3, NH4Cl, and H-2, a readily available dtbm-Segphos ruthenium catalyst can be used to prepare the desired chiral primary amine with >93% ee on multikilogram scale.

Automated summary

Direct asymmetric reductive amination is an efficient method for converting ketones to alpha-chiral primary amines, but reported examples are limited. This study developed two sets of Ru-catalyzed conditions for direct conversion of aryl methyl ketone to pharmaceutically relevant chiral primary amine, achieving >93% ee on multikilogram scale.