Regioselective Synthesis of (E)‑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 (E)-3-aminomethylene-2-thioxothiochroman-4-one derivatives (3) regioselectively at the C-3 position of 4-hydroxydithiocoumarin. Cycloaddition of product 3 with acetylene-1,4-dicarboxylate ester afforded adduct 6 regioselectively in good yields. Substrates 3a and 3e reacted with propargyl bromide (7) in the presence of potassium carbonate in acetone, giving the unusual products 8a and 8e. DFT calculations explored the mechanism of 3e 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.