Brønsted Acid Cocatalysts in Photocatalytic Radical Addition of α-Amino C–H Bonds across Michael Acceptors

Abstract

In marked contrast to the variety of strategies available for oxidation and nucleophilic functionalization of methylene groups adjacent to amines, relatively few approaches for modification of this position with electrophilic reaction partners have been reported. In the course of an investigation of the reactions of photogenerated α-amino radicals with electrophiles, we made the surprising observation that the efficiency of radical photoredox functionalization of N-aryl tetrahydroisoquinolines is dramatically increased in the presence of a Brønsted acid cocatalyst. Optimized conditions provide high yields and efficient conversion to radical addition products for a range of structurally modified tetrahydroisoquinolines and enones using convenient household light sources and commercially available Ru(bpy)3Cl2 as a photocatalyst. Our investigations into the origins of this unexpected additive effect have demonstrated that the carbon-carbon bond-forming step is accelerated by TFA and is a rare example of Brønsted acid catalysis in radical addition reactions. Moreover, a significant conclusion arising from these studies is the finding that product formation is dominated by radical chain processes and not by photocatalyst turnover. Together, these findings have important implications for the future design and mechanistic evaluation of photocatalytic radical processses.