Nontraditional Fragment Couplings of Alcohols and Carboxylic Acids: C()-C() Cross-Coupling via Radical Sorting.

Alcohols and carboxylic acids are among the most commercially abundant, synthetically versatile, and operationally convenient functional groups in organic chemistry. Under visible light photoredox catalysis, these native synthetic handles readily undergo radical activation, and the resulting open-shell intermediates can subsequently participate in transition metal catalysis. In this report, we describe the C()-C() cross-coupling of alcohols and carboxylic acids through the dual combination of -heterocyclic carbene (NHC)-mediated deoxygenation and hypervalent iodine-mediated decarboxylation. This mild and practical Ni-catalyzed radical-coupling protocol was employed to prepare a wide array of alkyl-alkyl cross-coupled products, including highly congested quaternary carbon centers from the corresponding tertiary alcohols or tertiary carboxylic acids. We demonstrate the synthetic applications of this methodology to alcohol -alkylation and formal homologation, as well as to the late-stage functionalization of drugs, natural products, and biomolecules.