Direct Enantioselective C(sp3)-H Acylation for the Synthesis of α-Amino Ketones.

Abstract

A direct enantioselective acylation of α-amino C(sp3)-H bonds with carboxylic acids has been achieved via the merger of transition metal and photoredox catalysis. This straightforward protocol enables cross-coupling of a wide range of carboxylic acids, one class of feedstock chemicals, with readily available N-alkyl benzamides to produce highly valuable α-amino ketones in high enantioselectivities under mild conditions. The synthetic utility of this method is further demonstrated by gram scale synthesis and application to late-stage functionalization. This method provides an unprecedented solution to address the challenging stereocontrol in metallaphotoredox catalysis and C(sp3)-H functionalization. Mechanistic studies suggest the α-C(sp3)-H bond of the benzamide coupling partner is cleavage by photocatalytically generated bromine radicals to form α-amino alkyl radicals, which subsequently engages in nickel-catalyzed asymmetric acylation.