Overcoming photocatalytic hydrogen atom transfer (HAT) limitations via formyl-group directed C‒H cleavage

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 lack of regioselectivity and inefficiency. Herein, we propose the HAcTive strategy to address these longstanding challenges. The fast HAT from aldehydes formyl group and ensuing α-fragmentation of the photogenerated acyl radical (i.e. decarbonylation) is exploited to boost efficiency, steer regioselectivity and enable reactivity in HAT-based methodologies. We validated this concept in several decarbonylative C‒C bond formation protocols. In-depth mechanistic investigation based on Laser-Flash Photolysis and Density Functional Theory highlight the crucial role of kinetic factors to control the observed chemistry.