Regioselective trifluoromethylation of N-heteroaromatic compounds using trifluoromethyldifluoroborane activator

Tomoaki Nishida, Haruka Ida, Yoichiro Kuninobu, Motomu Kanai

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Many important drugs, agrochemicals and their lead compounds contain trifluoromethyl group(s). Most processes currently used to access trifluoromethyl group-containing molecules are performed by substitution of the carboxy or trichloromethyl groups using hazardous fluorinating reagents under harsh reaction conditions. Cross-coupling reactions between organohalides or boronic acids/esters and trifluoromethylating reagents are also used. Direct C-H trifluoromethylation of organic molecules, however, is the ideal method of introducing trifluoromethyl group(s). Despite the recent advances in C-H trifluoromethylation of N-heteroaromatic compounds, regioselective C-H trifluoromethylation of six-membered heteroaromatic compounds has yet to be achieved. Herein we present a general and reliable method for the synthesis of trifluoromethyl group-containing N-heteroaromatics through highly regioselective addition of a trifluoromethyl nucleophile to pyridine, quinoline, isoquinoline and two or three heteroatom-containing N-heteroaromatic N-oxides activated by trifluoromethyldifluoroborane. The C-H trifluoromethylation proceeds under mild conditions in gram scale with high functional group tolerance. This method will be useful in both laboratory and industrial processes.

Original languageEnglish
Article number3387
JournalNature communications
Volume5
DOIs
Publication statusPublished - Mar 13 2014
Externally publishedYes

Fingerprint

Boronic Acids
Agrochemicals
Lead compounds
Nucleophiles
Molecules
Oxides
Functional groups
Esters
Substitution reactions
Cross Reactions
reagents
Pharmaceutical Preparations
lead compounds
nucleophiles
cross coupling
quinoline
esters
molecules
pyridines
drugs

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Regioselective trifluoromethylation of N-heteroaromatic compounds using trifluoromethyldifluoroborane activator. / Nishida, Tomoaki; Ida, Haruka; Kuninobu, Yoichiro; Kanai, Motomu.

In: Nature communications, Vol. 5, 3387, 13.03.2014.

Research output: Contribution to journalArticle

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