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

Abstract

An useful and expedient synthetic route for the synthesis of 4-methyl-3,4-dihydrothiopyran derivatives (3a-p & 6a-o) was accomplished from 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 sulphide (4) also provided the cyclized products (5a-e), whereas the reaction between 4-hydroxy-2H-chromene-2-thione and ethyl vinyl sulphide (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 DFT calculations has been carried out for the formation products to establish reaction mechanisms and reaction energy profiles. 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 broad substrate scope, high regioselectivity, moderate to good yields, high atom economy, mild reaction conditions, and shorter reaction time.