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

  • Angew Chem Int Ed Engl. 2020 Jul 27;59(31):12853-12859. doi: 10.1002/anie.202003271.
Han Seul Park  1 ,  Zhoulong Fan  1 ,  Ru-Yi Zhu  1 ,  Jin-Quan Yu  1
Affiliations
  • 1. Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
PMID: 32385966 DOI: 10.1002/anie.202003271
Abstract

Reported herein is the distal γ-C(sp3 )-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 γ-C(sp3 )-H olefination of ketone substrates. In addition, MPAAs enabled the γ-C(sp3 )-H olefination of free carboxylic acids to form diverse six-membered lactones. Besides alkyl carboxylic acids, benzylic C(sp3 )-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 γ-C(sp3 )-H olefinated products.

Keywords
C(sp3)−H activation; amino acids; olefins; palladium; synthetic methods.
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