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. 2022 Jul 13;144(27):11961-11968.
doi: 10.1021/jacs.2c04807. Epub 2022 Jul 5.

Deoxytrifluoromethylation of Alcohols

Nicholas E Intermaggio  1 , Agustin Millet  1 , Dali L Davis  1 , David W C MacMillan  1
Affiliations

Deoxytrifluoromethylation of Alcohols

Nicholas E Intermaggio et al. J Am Chem Soc. .

Abstract

Deoxy-functionalization of alcohols represents a class of reactions that has had a profound impact on modern medicine. In particular, deoxyfluorination is commonly employed as a means to incorporate high-value fluorine atoms into drug-like molecules. Recently, the trifluoromethyl (CF3) group has garnered attention from medicinal chemists due to its ability to markedly improve the pharmaceutical properties of small-molecule drug candidates. To date, however, there remains no general means to accomplish the analogous deoxygenative trifluoromethylation of alcohols. We report herein a copper metallaphotoredox-mediated direct deoxytrifluoromethylation, wherein alcohol substrates are activated in situ by benzoxazolium salts for C(sp3)-CF3 bond formation.

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Conflict of interest statement

The authors declare the following competing financial interest(s): D.W.C.M. declares a competing financial interest with respect to the integrated photoreactor.

Figures

Figure 1.
Figure 1.
Deoxytrifluoromethylation of alcohols.
Figure 2.
Figure 2.
Plausible mechanism for deoxytrifluoromethylation.
See this image and copyright information in PMC

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