The nitrogen inversion in fused isoxazolidinyl derivatives of substituted uracil: synthesis,NMR and computational analysis

A series of fused isoxazolidines have been prepared via 1,3-dipolar cycloaddition reactions of N-protected methylenenitrones with 1,3-dimethyluracil derivatives, and their NMR spectra have been recorded in TFA-d and in CDCl₃ over a wide range of temperatures. The spectra indicate the presence of two invertomers for all isoxazolidines. Barriers to nitrogen inversion in the cycloadduct 6a have been determined using DFT quantochemical calculations. Our estimates have shown that the inversion proceeds at more complex path, involving four structures of local minima and four transition states.