(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.
ASJC Scopus subject areas
- Organic Chemistry