Ketone Scope and Their Limitations in Transition Metal Catalyzed Direct Asymmetric Hydrogenative Aminations

Chiral amines are valuable building blocks in the manufacture of agrochemicals, pharmaceuticals, natural products, fine chemicals, functional materials among others. Compared to asymmetric hydrogenation of imines/enamides and biocatalytic/organocatalytic asymmetric reductive amination, transition metal catalyzed direct asymmetric hydrogenative amination reactions (DAHA) using molecular dihydrogen as the reductant are highly economical, atom and/or step-efficient and thus attractive for researchers from both industry and academia. In previous reviews, catalysts/methods development, applications in synthesis of pharmaceuticals and [N] source were summarized and discussed. In this review, we summarize and discuss the ketone substrates scope upon utilizing the state-of-the-art transition metal catalysts. The substrate limitations, potential applications and key mechanisms are also critically concluded.