Biocatalytic trifluoromethylation of unprotected phenols

• Published in: Nature communications Vol. 7; no. 1; p. 13323
• Main Authors: Simon, Robert C., Busto, Eduardo, Richter, Nina, Resch, Verena, Houk, Kendall N., Kroutil, Wolfgang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.11.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/77/603; 639/638/77/888; Chemistry; Humanities and Social Sciences; Methods; multidisciplinary; Phenols; Reagents; Science; Science (multidisciplinary); Zinc; United States > US; Austria; California
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13323

Organofluorine compounds have become important building blocks for a broad range of advanced materials, polymers, agrochemicals, and increasingly for pharmaceuticals. Despite tremendous progress within the area of fluorination chemistry, methods for the direct introduction of fluoroalkyl-groups into organic molecules without prefunctionalization are still highly desired. Here we present a concept for the introduction of the trifluoromethyl group into unprotected phenols by employing a biocatalyst (laccase), t BuOOH, and either the Langlois’ reagent or Baran’s zinc sulfinate. The method relies on the recombination of two radical species, namely, the phenol radical cation generated directly by the laccase and the CF 3 -radical. Various functional groups such as ketone, ester, aldehyde, ether and nitrile are tolerated. This laccase-catalysed trifluoromethylation proceeds under mild conditions and allows accessing trifluoromethyl-substituted phenols that were not available by classical methods. The introduction of fluorine into organic molecules often requires prefunctionalised molecules or protection of reactive functional groups. Here, the authors report a biocatalytic method for the trifluoromethylation of unprotected phenols under mild conditions.