Copper-catalysed regioselective S-alkylation and C–3(H) activation of 4-hydroxydithiocoumarins and 4-hydroxy-2H-chromene-2-thione: easy access to 4-methyl-3,4-dihydrothiopyran derivatives

Abstract

A useful and expedient synthetic route for the synthesis of 4-methyl-3,4-dihydrothiopyran derivatives (3a–p & 6a–o) was accomplished by employing 4-hydroxydithiocoumarins/4-hydroxy-2H-chromene-2-thione and substituted vinyl ethers in the presence of 10 mol% Cu(I) iodide catalyst in toluene under reflux conditions. Notably, the reaction between 4-hydroxydithiocoumarin and ethyl vinyl sulfide (4) provided the cyclized products 5a–e, whereas the reaction between 4-hydroxy-2H-chromene-2-thione and ethyl vinyl sulfide 4 gave only the hydrothiolation products 7a–c under identical reaction conditions. Similarly, the reaction of 4-hydroxydithiocoumarin with phenyl vinyl ether also provided the hydrothiolation products 3q–s instead of the expected cyclized products under similar reaction conditions. The present methodology involves the formation of two new C–C bonds and one C–S bond via regioselective S-alkylation and C-3 activation of 4-hydroxydithiocoumarin/4-hydroxy-2H-chromene-2-thione in a single step at the expense of one C–O/C–S bond. The current procedure possesses several positive features, such as a broad substrate scope, high regioselectivity, moderate to good yields, high atom economy, mild reaction conditions, and a shorter reaction time.