The Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides
Author(s)Cho, Eun Jin; Senecal, Todd D.; Kinzel, Tom; Zhang, Yong; Watson, Donald A.; Buchwald, Stephen Leffler; ... Show more Show less
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The trifluoromethyl group can dramatically influence the properties of organic molecules, thereby increasing their applicability as pharmaceuticals, agrochemicals, or building blocks for organic materials. Despite the importance of this substituent, no general method exists for its installment onto functionalized aromatic substrates. Current methods either require the use of harsh reaction conditions or suffer from a limited substrate scope. Here we report the palladium-catalyzed trifluoromethylation of aryl chlorides under mild conditions, allowing the transformation of a wide range of substrates, including heterocycles, in excellent yields. The process tolerates functional groups such as esters, amides, ethers, acetals, nitriles, and tertiary amines and, therefore, should be applicable to late-stage modifications of advanced intermediates. We have also prepared all the putative intermediates in the catalytic cycle and demonstrated their viability in the process.
available in PMC 2011 June 25.
DepartmentMassachusetts Institute of Technology. Center for Materials Science and Engineering; Massachusetts Institute of Technology. Department of Chemistry
American Association for the Advancement of Science
Cho, E. J., T. D. Senecal, T. Kinzel, et al. 2010The Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides. Science 328(5986): 1679–1681.
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