Direct β- and γ-C(sp3)-H Alkynylation of Free Carboxylic Acids

In this study we report the identification of a novel class of ligands for palladium-catalyzed C(sp(3))-H activation that enables the direct alkynylation of free carboxylic acid substrates. In contrast to previous synthetic methods, no introduction/removal of an exogenous directing group is required. A broad scope of acids including both alpha-quaternary and challenging alpha-non-quaternary can be used as substrates. Additionally, the alkynylation in the distal gamma-position is reported. Finally, this study encompasses preliminary findings on an enantioselective variant of the title transformation as well as synthetic applications of the products obtained.