β‐ and γ‐C(sp3)−H Heteroarylation of Free Carboxylic Acids: A Modular Synthetic Platform for Diverse Quaternary Carbon Centers

Abstract Pd II ‐catalyzed C(sp 3 )−H activation of free carboxylic acids represents a significant advance from conventional cyclopalladation initiated reactions. However, developing a modular synthetic platform for diverse quaternary and tertiary carbon centers based on this reactivity, two challenges remain to be addressed: mono‐selectivity in each consecutive C−H functionalization step; compatibility with heteroatoms. While the exclusive mono‐selectivity was achieved by β ‐lactonization/nucleophilic attack, the latter limitation remains to be overcome. Herein, we report the Pd II ‐catalyzed β‐ and γ ‐C(sp 3 )−H heteroarylation of free carboxylic acids using pyridine‐pyridone ligands capable of overcoming these limitations. A sequence of three consecutive C(sp 3 )−H activation reactions of pivalic acid provides an unique platform for constructing diverse quaternary carbon centers containing heteroaryls which could serve as an enabling tool for escaping the flat land in medicinal chemistry.