Enantioselective multicomponent 1,2-arylaminoalkylation of acrylates by photoredox/nickel dual catalysis

<h2>Summary</h2> γ-aminobutyric acid (GABA) and its derivatives are important central nervous system neurotransmitters; hence, the development of enantioselective methods for the efficient synthesis of substituted GABAs is highly desirable. Here, we present a photoredox/Ni dual-catalyzed enantioselective cross-coupling of acrylates with (hetero)aryl iodides and α-silyl alkylamines, furnishing chiral α-aryl-substituted γ-amino esters in good to excellent enantioselectivities. Key to the arylaminoalkylation process is the stabilizing effect provided by the adjacent nitrogen atom for primary alkyl radicals, rendering them compatible in this multicomponent protocol. This redox-neutral protocol exhibits broad and complementary functional group tolerance, and its synthetic utility is highlighted through diversification of complex biologically active compounds and concise synthesis of functional molecule intermediates. Preliminary mechanistic studies, including radical trapping, radical clock, luminescence quenching, and cyclic voltammetry experiments as well as reactions with isolable nickel complexes, support the radical nature of the transformation with an operative Ni(0)/Ni(I)/Ni(III) pathway.