Decarboxylative and Deformylative Alkyl–Alkyl Cross-Coupling Enabled by Nickel/Photoredox Catalysis

Alkyl carboxylic acids and aldehydes are among the most fundamental functional groups in organic chemistry. Their combined use as coupling fragments offers new opportunities for the construction of valuable C(sp3)–C(sp3) bonds, yet it remains unexplored. Here, we report a radical C(sp3)–C(sp3) cross-coupling of redox-active esters derived from carboxylic acids with 4-alkyl-dihydropyridines derived from aldehydes and enabled by nickel/photoredox dual catalysis in a redox-neutral manner. This mild and practical radical-coupling protocol is applicable for forging C(sp3)–C(sp3) bonds across a wide range of substrates, including 1°–1°, 1°–2°, and 1°–3° couplings, thereby allowing for facile access to a wide array of C(sp3)-enriched motifs, including highly congested quaternary carbon centers. The synthetic utility of this methodology is further demonstrated through the streamlined synthesis of several known compounds as well as its application in building distinctive 1,2-heteroatom carbon frameworks and C(sp3)–glycosides.