SodiumChlorodifluoroacetate.PDFVIP

ORGANIC LETTERS Terms of Use CC-BY ? ? 2013 S ,N, and Se-Difluoromethylation Using Vol. 15, No. 19 Sodium Chlorodifluoroacetate 5036–5039 Vaibhav P. Mehta and Michael F. Greaney* School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, U.K. Michael.Greaney@manchester.ac.uk Received August 18, 2013 ABSTRACT A simple protocol for the difluoromethylation of thiols is reported using chlorodifluoroacetate as the difluoromethylating agent. This cheap reagent undergoes smooth decarboxylation at 95 °C to afford difluorocarbene, which can be trapped with a variety of aromatic and heteroaromatic thiols. The reaction is also effective for the difluoromethylation of heterocyclic nitrogen compounds and phenylselenol. Selective fluorination is an important method for control- formation5 stimulated us to examine fluoroacetate deriva- ling molecular function and properties. Biological activities tives in this regard. Trifluoroacetic acid and its salts are bulk such as potency, log D, and metabolic stability can fre- chemicals that can be sourced at low cost and have demon- quently be modulated through the selective incorporation of strated utility in selective trifluoromethylations.6 We were fluorine-containing groups,1 cre