α-(trifluoromethyl)amine derivatives via nucleophilic trifluoromethylation of nitrones

D. W. Nelson*, J. Owens, D. Hiraldo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

(Trifluoromethyl)trimethylsilane (TMSCF3) reacts with nitrones to afford α-(trifluoromethyl)hydroxylamines protected as O-trimethylsilyl ethers. Potassium t-butoxide initiates the nucleophilic trifluoromethylation. The reaction works best with α,N-diaryl nitrones, and the conditions are compatible with a range of substituents on the aryl groups. Acidic deprotection of the nitrone/TMSCF3 adducts generates α-(trifluoromethyl)hydroxylamines. Catalytic hydrogenation of the adducts produces α-(trifluoromethyl)amines. Nitrone/TMSCF3 adducts with strong electron-withdrawing groups on the α-aryl ring or heterocyclic α-aryl groups undergo an elimination/addition sequence to generate α, α-bis(trifluoromethyl)amines. Nitrones with alkyl groups bound directly to the 1,3-dipolar moiety fail to react with TMSCF3, but trifluoromethylation of β,γ-unsaturated nitrones followed by reduction of the double bond can circumvent this limitation.

Original languageEnglish (US)
Pages (from-to)2572-2582
Number of pages11
JournalJournal of Organic Chemistry
Volume66
Issue number8
DOIs
StatePublished - Apr 20 2001

ASJC Scopus subject areas

  • Organic Chemistry

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