Regio- and stereo-selective synthesis of trifluoromethylated isoxazolidines by 1,3-dipolar cycloaddition of 1,1,1-trifluoro-3-phenylsulfonylpropene with nitrones, and their conversion into trifluoromethylated syn-3-amino alcohols

Abstract

1,1,1-Trifluoro-3-phenylsulfonylpropene 1, a useful synthetic precursor for trifluoromethylated compounds, has been prepared from methyl phenyl sulfone 2 and ethyl trifluoroacetate. The 1,3-dipolar cycloaddition of 1 with various nitrones 5a–f gave 5-trifluoromethylisoxazolidines 6a–f with a high degree of regio- and stereo-selectivity. The adducts 6a–f were converted into trifluoromethylated syn-3-amino alcohols 8a–d by desulfonylation with Na–Hg, followed by reductive cleavage of the N–O bond by catalytic hydrogenation. Conversion of 8a and 8d into the cyclic carbamates 10a and 10d confirmed the assigned stereochemistry of 8 and, hence, of the cycloadduct 6a–f.