Biocatalytic trifluoromethylation of unprotected phenols.
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), tBuOOH, 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 CF3-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.
Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, NAWI Graz, BioTechMed Graz, Heinrichstrasse 28, 8010-Graz, Austria.
Robert C
RC
Simon
Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, NAWI Graz, BioTechMed Graz, Heinrichstrasse 28, 8010-Graz, Austria.
Eduardo
E
Busto
ACIB GmbH, c/o Heinrichstrasse 28, 8010-Graz, Austria.
Nina
N
Richter
Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, NAWI Graz, BioTechMed Graz, Heinrichstrasse 28, 8010-Graz, Austria.
Verena
V
Resch
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
Kendall N
KN
Houk
Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, NAWI Graz, BioTechMed Graz, Heinrichstrasse 28, 8010-Graz, Austria.
Wolfgang
0000-0002-2151-6394
W
Kroutil