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Synthesis of 3-[(4-Nitrophenyl)thio]-Substituted 4-Methylene-1-pyrrolines from N-Propargylic beta-Enaminones

A facile and efficient method for the synthesis of 3-[(4-nitrophenyl)thio]-substituted 4-methylene-1-pyrrolines is described. When treated with 4-nitrobenzenesulfenyl chloride in refluxing acetonitrile, N-propargylic beta-enaminones produced alpha-sulfenylated N-propargylic beta-enaminones, which, in the presence of sodium hydride or cesium carbonate, underwent nucleophilic cyclization to afford 4-methylene-3-[(4-nitrophenyl)thio]-1-pyrrolines in good to high yields. It was shown for the first time that on N-propargylic beta-enaminone systems, alpha-sulfenylation dominates over the formation of thiirenium ion. This one-pot two-step process was found to be general for a variety of N-propargylic beta-enaminones and demonstrated good tolerance to a diversity of aromatic and heteroaromatic groups with electron-withdrawing and electron-donating substituents. This process is also applicable to the cyclization of internal alkyne-tethered N-propargylic beta-enaminones. The enrichment of 1-pyrroline core with an aryl sulfide moiety might exhibit potential for the synthesis of molecules of pharmacological interest.