Dual NHC/HAT-Promoted Esterification to Access α-Aryl Glycines

Abstract

α-Aryl glycines are among the more important carbonyl compounds, particularly as nonproteinogenic α-amino acids present in many pharmacophores. As such, many strategies have been developed to access this motif, but direct carboxylation methods remain underdeveloped. Herein, we employ a dual NHC/HAT catalysis strategy to access 2-azaallyl radicals, which subsequently couple with in situ generated ester azolium radical intermediates. Base-mediated collapse of the ensuing tetrahedral intermediate liberates the NHC catalyst and benzophenone protected aryl glycine. This methodology was employed to esterify obtain a variety of aryl substituted glycine derivatives, as well as allylic and benzylic sites. Mechanistic studies reveal that this radical process operates under both oxidative and reductive quenching cycles, while preliminary experiments employing a chiral NHC and Lewis acid additive demonstrate modest enantioselectivity.