Asymmetric 1,3-dipolar cycloaddition of optically active trifluoromethylated α,β-unsaturated aryl sulfones with nitrones: the use of o-dialkylaminoethyl chiral auxiliaries

Abstract

Optically active trifluoromethylated α,β-unsaturated aryl sulfones 8a–c, which have a chiral N,N-dialkylaminoethyl group on the ortho position, were synthesized from (S)-1-phenylethylamine 2 and ethyl trifluoroacetate. Asymmetric 1,3-dipolar cycloaddition of sulfones 8a–c with some selected nitrones 9a–c gave the corresponding isoxazolidines 10a–c, 11a–c and 12–15 regio- (> 98%) and diastereo-selectively (36–56% de) in 58–80% yields. The absolute configurations of the cycloadducts were assigned on the basis of X-ray crystallographic analysis of the adduct 10a and by the ¹H NMR spectra. The obtained facial selectivity was rationalized by comparison of four possible stable conformers of compound 8a based on AM1 calculations.