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

Abstract

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.

Keywords

Alkenes / Radical-radical coupling / Deoxygenation / Photocatalysis / Carboxylic acid / Difunctionalization / Synergistic catalysis / Ketone

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