A Highly Regioselective Three‐Component Radical Coupling of Alkenes with Carboxylic Acids and Their Derivatives

Comprehensive Summary Radical coupling of alkenes provides a powerful platform for constructing multiple bonds in a single operation, enabling the rapid generation of molecular complexity. However, controlling chemo‐ and regioselectivity remains a key challenge in this approach, especially when multicomponent radical intermediates are involved. Herein, a visible‐light induced regioselective alkyl‐acylation of alkenes has been developed by using carboxylic acids and their derivatives (NHPI ester) as the coupling partners. This synergistic combination of decarboxylation of NHPI esters and phosphoranyl radical‐mediated deoxygenation protocol requires no external oxidants or reductants, and facilitating the generation of alkyl radical and acyl radical under mild and redox‐neutral conditions. A wide range of highly functionalized ketone products have been constructed in good yields with high regioselectivity from readily available carboxylic acids and alkenes. The mechanistic studies support a radical cascade pathway involving two photogenerated radicals and alkenes, and DFT calculations demonstrate that the high regioselectivity arises from kinetically controlled radical addition and radical/radical cross‐coupling process. In addition, this strategy can be explored to realize regioselective radical dialkylation of alkenes, producing molecules with sterically congested all‐carbon quaternary centers in moderate yields. This robust strategy exhibits excellent functional group tolerance, gram‐scale ability, and has been applied in the late‐stage functionalization of bioactive natural compounds, thereby providing a new approach to functionalized ketones from carboxylic acids and derivatives.