Ligand-Enabled beta-C(sp(3))-H Olefination of Free Carboxylic Acids

An acetyl-protected aminoethyl phenyl thioether has been developed to promote C(sp(3))-H activation. Significant ligand enhancement is demonstrated by the realization of the first Pd(II)-catalyzed olefination of C(sp(3))-H bonds of free carboxylic acids without using an auxiliary. Subsequent lactonization of the olefinated product via 1,4 addition provided exclusively monoselectivity in the presence of multiple beta-C-H bonds. The product gamma-lactone can be readily opened to give either the highly valuable beta-olefinated or gamma-hydroxylated aliphatic acids. Considering the challenges in developing Heck couplings using alkyl halides, this reaction offers a useful alternative.