Synthesis of N-trifluoromethyl amides from carboxylic acids

Liu, Jianbo; Parker, Matthew F.L.; Wang, Sinan; Flavell, Robert R.; Toste, F. Dean; Wilson, David M.

doi:10.1016/j.chempr.2021.07.005

Synthesis of N-trifluoromethyl amides from carboxylic acids

Journal Article · Tue Aug 03 00:00:00 EDT 2021 · Chem

DOI:https://doi.org/10.1016/j.chempr.2021.07.005· OSTI ID:1987292

Liu, Jianbo ^[1]; Parker, Matthew F.L. ^[2]; Wang, Sinan ^[2]; Flavell, Robert R. ^[2]; Toste, F. Dean ^[3]; Wilson, David M. ^[2]

First Affiliated Hospital of Sun Yat-Sen University, Guangzhou (China); Univ. of California, San Francisco, CA (United States)
Univ. of California, San Francisco, CA (United States)
Univ. of California, Berkeley, CA (United States)

Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE: National Institutes of Health (NIH)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1987292

Journal Information:: Chem, Journal Name: Chem Journal Issue: 8 Vol. 7; ISSN 2451-9294

Publisher:: Cell PressCopyright Statement

Country of Publication:: United States

Language:: English

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
N-trifluoromethyl amides
acylation
alkyl bromide
alpha-carbonyl
alpha-heteroaryl
amide-bond formation
carboxylic acids
isothiocyanates
silver fluoride

Synthesis of N-trifluoromethyl amides from carboxylic acids

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References (27)

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