Abstract
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.
Highlights
Organofluorine compounds have become important building blocks for a broad range of advanced materials, polymers, agrochemicals, and increasingly for pharmaceuticals
Several excellent methods to provide structurally diverse CF3building blocks have been elaborated[6,7,8]: common strategies to introduce the CF3-group into aromatic compounds involve metal-mediated/catalysed functional group interconversions[9,10] where halogens[11,12,13], boronic acids[14,15,16], boronates[17,18] and even amines[19,20] are replaced by nucleophilic, electrophilic or radical CF3-sources (Fig. 1a)
We report an efficient and selective method for trifluoromethylation of unprotected phenols by biocatalytic introduction of a trifluoromethyl group derived from common precursors
Summary
Organofluorine compounds have become important building blocks for a broad range of advanced materials, polymers, agrochemicals, and increasingly for pharmaceuticals. 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. The introduction of fluoroalkyl-groups (for example, CF3, CHF2, CH2F, etc.) into organic compounds has become a major subject in various fields of chemical research, in particular medicinal chemistry and drug discovery[1,2]. This is due to the metabolic stability, increased permeability or enhanced binding properties of the organo-fluorine compounds in comparison to their non-fluorinated counterparts[3]. We report an efficient and selective method for trifluoromethylation of unprotected phenols by biocatalytic introduction of a trifluoromethyl group derived from common precursors
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