Distal γ-C(sp3)-H Olefination of Ketone Derivatives and Free Carboxylic Acids

Reported herein is the distal gamma-C(sp(3))-H olefination of ketone derivatives and free carboxylic acids. Fine tuning of a previously reported imino-acid directing group and using the ligand combination of a mono-N-protected amino acid (MPAA) and an electron-deficient 2-pyridone were critical for the gamma-C(sp(3))-H olefination of ketone substrates. In addition, MPAAs enabled the gamma-C(sp(3))-H olefination of free carboxylic acids to form diverse six-membered lactones. Besides alkyl carboxylic acids, benzylic C(sp(3))-H bonds also could be functionalized to form 3,4-dihydroisocoumarin structures in a single step from 2-methyl benzoic acid derivatives. The utility of these protocols was demonstrated in large scale reactions and diversification of the gamma-C(sp(3))-H olefinated products.