Three-Component Synthesis of γ-Amino Esters with α-Quaternary Carbon Centers via NHC/Photoredox Dual Catalysis

γ-Amino acid derivatives are important motifs in medicinal chemistry and have shown wide applicability as inhibitory neurotransmitters. An important class of these compounds feature α,α-disubstitution. However, established routes for the direct synthesis of γ-amino esters bearing α-quaternary centers are severely limited in both number of available routes and scope of the transformation. Herein we present a method for the three-component synthesis of α,α-disubstituted γ-amino esters via NHC/photoredox dual catalysis. This reaction involves in-situ formation of an acyl azolium ester which undergoes photocatalytic reduction to the key stabilized alkoxycarbonyl radical. This methodology was shown to be capable of synthesizing a wide variety of γ-amino esters with various α-quaternary centers in moderate to good yields, including a derivative of the drug loperamide. The diversity of products that can be synthesized facilitates the rapid generation of libraries of γ-amino acid derived compounds.)).