Stereospecific synthesis of 2,3-dimethyl-1,4-thiamorpholines by cyclization of β-n-methoxycarbonylaminoalkyl vinyl sulfoxides and related compounds

Abstract

Synthesis of cis- and trans-N-methoxycarbonyl-2, 3-dimethyl-l, 4-thiamorpholine and their S-oxides and S, S-dioxides by intramolecular reaction of the corresponding 2-methoxy-carbonylaBinoalkyl-2' -chloroethyl thioethers, sulfoxides and sulfones with sodium hydride in dimethylformamide at room temperature is reported. Cyclization of chlorothioethers and -sulfones is Stereospecific although, in the case of sulfones, the formed 1, 4-thiamorpholines S, S-dioxides epimerize at C(2) after long reaction times. In chlorosulfoxides, elimination of HCl is previous to cyclization which also resulted stereospecific except in the case of the acyclic starting material of R*s,S*1,S*2 configuration, where epimerization at sulfur takes place.