α-(Trifluoromethyl)amine Derivatives via Nucleophilic Trifluoromethylation of Nitrones
- 17 March 2001
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 66 (8) , 2572-2582
- https://doi.org/10.1021/jo000685l
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.Keywords
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