TY - JOUR
T1 - Deoxytrifluoromethylation of Alcohols
AU - Intermaggio, Nicholas E.
AU - Millet, Agustin
AU - Davis, Dali L.
AU - MacMillan, David W.C.
N1 - Funding Information:
The authors are grateful for financial support provided by the National Institute of General Medical Sciences (NIGMS), the NIH (under Award R35GM134897-02), the Princeton Catalysis Initiative, and kind gifts from Pfizer, MSD, Janssen, Bristol-Myers Squibb, and Genentech. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS. N.E.I. and D.L.D. thank Princeton Universty, E. Taylor, and the Taylor family for an Edward C. Taylor Fellowship. A.M. acknowledges support from BioLEC (Bioinspired Light-Escalated Chemistry), an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, under Award #DE-SC0019370. The authors thank Z. Dong, P. Sarver, and V. Bacauanu for helpful scientific discussions, B. Li and H. Sakai for graphic design support, and R. Lambert for assistance in preparing the manuscript.
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/7/13
Y1 - 2022/7/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85134426847&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85134426847&partnerID=8YFLogxK
U2 - 10.1021/jacs.2c04807
DO - 10.1021/jacs.2c04807
M3 - Article
C2 - 35786873
AN - SCOPUS:85134426847
SN - 0002-7863
VL - 144
SP - 11961
EP - 11968
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 27
ER -