title: A scalable and operationally simple radical trifluoromethylation.
abstract: The large number of reagents that have been developed for the synthesis of trifluoromethylated compounds is a testament to the importance of the CF3 group as well as the associated synthetic challenge. Current state-of-the-art reagents for appending the CF3 functionality directly are highly effective; however, their use on preparative scale has minimal precedent because they require multistep synthesis for their preparation, and/or are prohibitively expensive for large-scale application. For a scalable trifluoromethylation methodology, trifluoroacetic acid and its anhydride represent an attractive solution in terms of cost and availability; however, because of the exceedingly high oxidation potential of trifluoroacetate, previous endeavours to use this material as a CF3 source have required the use of highly forcing conditions. Here we report a strategy for the use of trifluoroacetic anhydride for a scalable and operationally simple trifluoromethylation reaction using pyridine N-oxide and photoredox catalysis to affect a facile decarboxylation to the CF3 radical.
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Beatty
authors.affiliation: 1] Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA [2] Small Molecule Design and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Douglas
authors.affiliation: Small Molecule Design and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Cole
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Corey R J
authors.initials: CR
authors.lastname: Stephenson
mesh_terms: D000089:Acetic Anhydrides / Q000737:chemistry*; D002384:Catalysis; D003653:Decarboxylation; D005463:Fluoroacetates / Q000737:chemistry*; D054879:Halogenation; D008745:Methylation; D010084:Oxidation-Reduction; D011725:Pyridines / Q000737:chemistry
chemical_list: D000089:Acetic Anhydrides; D005463:Fluoroacetates; D011725:Pyridines; C017958:trifluoroacetic anhydride; C013229:pyridine N-oxide