A Decarbonylative Strategy to Enhance Efficiency and Regioselectivity in Photocatalyzed Hydrogen Atom Transfer

Photocatalyzed hydrogen atom transfer (HAT) is now an established methodology in the synthesis of pharmaceuticals and agrochemicals as well as in the development of late-stage functionalization campaigns. Yet, the realization of the full potential of this manifold is held back by intrinsic challenges that still demand meticulous exploration and resolution, such as the lack of regioselectivity and inefficiency. Herein, we address these limitations by proposing a decarbonylative strategy. The fast direct HAT from aldehydes formyl group and ensuing α-fragmentation of the photogenerated acyl radical (i.e., decarbonylation) is exploited to boost efficiency, redirect regioselectivity, and enable reactivity in methodologies based on HAT. We validated this concept for decarbonylative C-C bond formation. In-depth mechanistic investigation based on laser-flash photolysis and density functional theory highlights the crucial role of kinetic factors in controlling the observed chemistry. Our work demonstrates that the exceptional hydrogen atom-donating ability of aldehydes can be harnessed to redefine paradigms in HAT photocatalysis.