Metal‐free Reaction of Allenamides with In‐Situ Formed Trifluoromethylnitrones as a Route to Highly Functionalized Isoxazolidines

Abstract

An additive‐free three‐component reaction of allenamides with in situ generated trifluoromethylnitrones has been uncovered. The reaction afforded an interesting class of trifluoromethylated methyleneisoxazolidines under mild conditions. Additionally, a gram‐scale reaction and the reductive transformation of trifluoromethylated isoxazolidines to aminomethylated allyl alcohol illustrate the high synthetic utility of the present synthetic strategy.

Trifluoromethylnitrone: a versatile building block for synthesizing trifluoromethyl-containing heterocyclic compounds

“…In 2023, the same research group extended the scope of trifluoromethylated methyleneisoxazolidine (27) synthesis and reported an additive-free MCR involving allenamides (26) and in situ generated trifluoromethylnitrones (3c). 57 This attractive approach resulted in the synthesis of trifluoromethylated methyleneisoxazolidines (27) under mild conditions (Scheme 4B). Allenamides (26), recognized as multifunctional synthetic reagents for metal-catalyzed reactions involving carbocyclic and heterocyclic rings, have gained attention.…”