Transition metal-free, base mediated one-pot approach for the construction of the benzo[b][1,4,5]oxathiazepine 1-oxide core.

Abstract

Herein, we have developed a base mediated, transition metal-free intermolecular epoxide ring opening by the nucleophilic attack of ortho-halogenated NH-sulfoximine followed by intramolecular aromatic nucleophilic substitution (SNAr) for the synthesis of separable diastereomers of selected benzo[b][1,4,5]oxathiazepine 1-oxides. Both C-N and C-O bonds are formed simultaneously in a single step. This strategy has a good substrate scope and requires simple reaction conditions (room temperature) and cost-effective reagents, and shows good applicability for accessing sulfoximine analogues of benzoxathiazepine 1-oxide like bioactive skeletons. The absolute configurations of the separable major isomer 4z (R,R), minor isomer 4z' (R,S) and single isomer 4r (R,R,S) were confirmed by 2D NMR. On the other hand, the relative configuration of 4q (S,R) was assigned by 2D NMR along with X-ray crystal data analysis.