Transition-Metal-Catalyzed Asymmetric Couplings of α-Aminoalkyl Fragments to Access Chiral Alkylamines

Enantiomerically pure alkylamines are pivotal structural elements in a broad range of pharmaceuticals, agrochemicals, natural products, and chemical building blocks. The development of useful methodologies for the preparation of these alkyamines is one of the central and long-standing challenges facing synthetic chemistry. In recent years, transition-metal-catalyzed enantioselective coupling reactions of α-aminoalkyl species have emerged as appealing C–C bond-forming approaches for the construction of chiral alkylamines. This useful technique is remarkable for its substantial advantages in functional group compatibility, substrate scope, molecular complexity, and synthetic practicality, which provides complementarity and orthogonality to traditional metal-catalyzed approaches to chiral amine synthesis. This Review underscores recent advances in transition-metal-catalyzed asymmetric alkylamine bond forming reactions organized by the type of key α-aminoalkyl intermediates, including (1) couplings of α-aminoalkyl-metal species, (2) couplings of α-aminoalkyl radicals, (3) couplings of imines with carbon electrophiles, and (4) couplings of enamines mediated by M–H species. In addition, the synthetic practicalities of such remarkable tools have also been highlighted by the total syntheses of selected natural and biologically interesting molecules and the stereoselective assembly of challenging target compounds.