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(sp3 )-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 α-quaternary and challenging α-non-quaternary can be used as substrates. Additionally, the alkynylation in the distal γ-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.