Non-pericyclic cycloaddition of gem-difluorosubstituted azomethine ylides to the CO bond: computational study and synthesis of fluorinated oxazole derivatives

Abstract

The cycloaddition of arenecarbaldehydes and α,α,α-trifluoroacetophenones with gem-difluoro-substituted azomethine ylides, generated from N-benzhydrylideneamines and difluorocarbene, occurs regioselectively to give, after hydrolysis, oxazolidin-4-ones. The primary cycloadducts of trifluoroacetophenones, 4,4-difluoro-5-trifluoromethyloxazolidine derivatives, are sufficiently stable to be isolated in reasonable to excellent yields. The results of correlation analysis and DFT calculations reveal a non-pericyclic step-wise mechanism of the reaction. The replacement of the two geminal hydrogen atoms in the azomethine ylide intermediate for fluorine atoms results in a dramatic change in the reaction mechanism from pericyclic to step-wise, proceeding via a zwitterion-like transition state in which no C–O bonding is observed.