Sterically Controlled C(sp2)–H Carboxylation and Formylation: A Complementary Strategy to SEAr Approaches

Carboxyl (–COOH) and Formyl (–CHO) substituted arenes are key structural motifs in organic chemistry, typically prepared via electrophilic aromatic substitution (SEAr) reactions or via transition-metal-catalyzed cross-coupling methodologies that require pre-functionalized starting materials. SEAr reactions hold tremendous synthetic value and one of their key advantages is their predictable regioselectivity originated from their well understood mechanistic pathway. However, certain positions still remain out of reach, such as sterically accessible but comparably electron-poor arene positions. Hence, we describe a nondirected C(sp2)–H carboxylation and formylation of arenes enabled by a dual ligand-based catalyst. By reoptimizing the steric control of our nondirected olefination of arenes along with two distinct protocols for subsequent oxidative cleavage of alkenes, a complementary set of regioisomeric products can be generated. The synthetic utility of this method is demonstrated by a broad scope with suitability for late-stage functionalization.