Additions to Racemates: A Strategy for Developing Asymmetric Cross-Coupling Reactions

Abstract

In this Account, the authors describe their progress in developing catalytic asymmetric C(sp3)–C(sp3) and C(sp3)–C(sp2) cross-coupling reactions. Whereas most catalytic enantioselective transformations rely on prochiral or meso starting materials, strategies that use racemic starting materials are rare. Key features of these reactions are efficient mechanisms for deracemization. Here, the authors present copper-catalyzed alkylation and rhodium-catalyzed Suzuki–Miyaura-type arylation reactions, their underlying mechanisms, and their applications in complex-molecule syntheses.

Copper-Catalyzed Enantioconvergent Radical N-Alkylation of Diverse (Hetero)aromatic Amines

“…Particularly, strategies are even less focused on enantioconvergent cross-coupling of racemic alkyl halides to generate chiral three-dimensional molecules of importance in drug discovery and material science (Scheme A). In this aspect, 3d transition metal catalysis provides an ideal tool for enantioconvergence by converting a pair of racemic alkyl halides into the same prochiral alkyl radical via a single electron transfer (SET) process . Although great efforts have been devoted to this field in the past two decades, extension to a general strategy is still a long-standing goal due to the restriction on the scope of coupling reagents.…”