Regioselective Synthesis of (<i>E</i>)-3-((Alkylamino)methylene)-2-thioxothiochroman-4-one Derivatives and Their Regioselective Cycloaddition with Alkynes

The catalyst-free reaction between 4-hydroxydithiocoumarin and isocyanide was investigated, yielding substituted (<i>E</i>)-3-aminomethylene-2-thioxothiochroman-4-one derivatives (<b>3</b>) regioselectively at the C-3 position of 4-hydroxydithiocoumarin. Cycloaddition of product <b>3</b> with acetylene-1,4-dicarboxylate ester afforded adduct <b>6</b> regioselectively in good yields. Substrates <b>3a</b> and <b>3e</b> reacted with propargyl bromide (<b>7</b>) in the presence of potassium carbonate in acetone, giving the unusual products <b>8a</b> and <b>8e</b>. DFT calculations explored the mechanism of <b>3e</b> formation and its reaction energy profile with alkynes. This protocol offers a broad substrate scope, good yields, ease of handling, catalyst-free conditions, high atom economy, regioselectivity, and a shorter reaction time.