Direct Synthesis of Tri-/Difluoromethyl Ketones from Carboxylic Acids by Cross-Coupling with Acyloxyphosphonium Ions |
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Authors: | Xanath Ispizua-Rodriguez Dr Socrates B Munoz Dr Vinayak Krishnamurti Dr Thomas Mathew Prof?Dr G K S Prakash |
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Institution: | 1. Department of Chemistry, Loker Hydrocarbon Research Institute, University of Southern California, 837 Bloom Walk, Los Angeles, CA-90089-1661 USA;2. Department of Chemistry, Kansas State University, 322 CBC Bldg, Manhattan, KS66506-0401 USA |
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Abstract: | A simple and straightforward approach to the synthesis of trifluoromethyl and difluoromethyl ketones from widely available carboxylic acids is disclosed. The transformation utilizes an acyloxyphosphonium ion as the active electrophile, conveniently generated in situ from the carboxylic acid substrate by using commodity chemicals. The utility of the reaction system is exemplified by its chemoselectivity, with tolerance to a variety of important functional groups. The late-stage functionalization of carboxylic acid active pharmaceutical ingredients and pharmaceutically relevant compounds is also discussed. |
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Keywords: | acyloxyphosphonium carboxylic acids copper difluoromethyl ketones TMSCF3 trifluoromethyl ketones |
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