The Direct Pd-Catalyzed γ-Lactonization of Aliphatic Carboxylic Acids

A direct palladium-catalyzed γ-lactonization of free carboxylic acids via C–O reductive elimination as a key step is described. Notable aspects of this protocol include the use of convenient and easily available sodium percarbonate as an oxidant and the development of a new beta-alanine derived ligand. The reported method enables the functionalization of a wide range of aliphatic acids including previously inaccessible β-non-quaternary acids. The regioselectivity and consequently substrate scope of this protocol proved complementary to established routes for the direct lactonization of aliphatic carboxylic acids. A modification of this method furthermore enables a direct β-C(sp3)–H hydroxylation of challenging α-non-quaternary carboxylic acids with considerable functional group tolerance. Through this report valuable compound libraries of γ-lactones and β-hydroxy acids with potential applications in various fields become available.