Enantioselective alkylation of α-amino C(sp3)−H bonds via photoredox and nickel catalysis

The catalytic enantioselective construction of C(sp3)−C(sp3) bonds remains a substantial challenge in organic synthesis. One particularly promising approach is the use of transition-metal-catalysed C(sp3)−H functionalization. However, a general strategy for the enantioselective alkylation of non-acidic C(sp3)−H bonds has yet to be developed. Here we present a unified platform for the enantioselective (trideutero)methylation and alkylation of α-amino C(sp3)–H bonds, using a combination of photoredox and nickel catalysis with widely available redox-active esters. This technique activates two coupling agents to form carbon-centred radicals, which are then asymmetrically coupled by a chiral nickel catalyst. This strategy is unique in its ability to separately control radical generation and cross-coupling, facilitating the use of transiently generated alkyl radicals, including highly reactive methyl radicals, in asymmetric catalysis, and thereby expediting the synthesis of enantioenriched bioactive alkaloids and offering a promising method for advancing asymmetric C(sp3)−C(sp3) bond formation. The use of a transition-metal catalyst for enantioselective alkylation of non-acidic C(sp3)–H bonds remains a challenge in organic synthesis. Now, the authors present a platform for the enantioselective (trideutero)methylation and alkylation of α-amino C(sp3)–H bonds via nickel-photoredox catalysis.