Distal γ-C(sp3)−H Olefination of Ketone Derivatives and Free Carboxylic Acids |
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Authors: | Han Seul Park Dr Zhoulong Fan Dr Ru-Yi Zhu Prof Dr Jin-Quan Yu |
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Institution: | Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA |
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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. |
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Keywords: | C(sp3)−H activation amino acids olefins palladium synthetic methods |
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