A scalable and operationally simple radical trifluoromethylation

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., USA

• Joel W. Beatty¹
• James J. Douglas^1,2
• Kevin P. Cole²
• Corey R. J. Stephenson¹

• ¹ Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
• ² Small Molecule Design and Development, Lilly Research Laboratoires, Eli Lilly and Company, Indianapolis, Indiana 46285, USA

• Request a Brochure
• Request more Info
• Request a Quote