Stereoselective synthesis of 4H-3,1-benzothiazines via tandem nucleophilic addition/epoxy ring-opening cyclization reactions of 2-(3-phenyloxiranyl)phenyl isothiocyanates

Abstract

Tandem nucleophilic addition/epoxy ring-opening cyclization reactions of 2-(3-phenyloxiranyl)phenyl isothiocyanates to produce 4-hydroxy(phenyl)methyl-4H-3,1-benzothiazines were investigated. In the reactions, carbon, sulfur, nitrogen, and oxygen nucleophiles were introduced at the 2-position of the benzothiazines, together with the two adjacent stereogenic centers arising from the epoxy carbon centers. We also found an interesting stereospecific rearrangement of 2-(alkylamino)-4-hydroxy(phenyl)methyl- 4H-3,1-benzothiazines to 1-alkyl-3-(2-(trans-3-phenylthiiran-2-yl)-phenyl)urea.