Stereoselective synthesis of naturally occurring unsaturated amide alkaloids by a modified Ramberg–Bäcklund reaction

Abstract

A convenient and rapid approach for the synthesis of naturally occurring unsaturated amide alkaloids 1a–1n by the recently developed one-flask Ramberg–Bäcklund reaction is described. The starting material was alcohol 3, which was transformed into thiolacetate 4 using the Mitsunobu reaction. In situ cleavage of acetyl moiety of 4, followed by alkylation of the resulting thiol with appropriate chloroacetamide 5, provided the sulfide 6. Oxidation of sulfide 6 gave the corresponding sulfone 2. Treatment of the sulfone 2 with the dibromodifluoromethane in the presence of alumina-supported potassium hydroxide in dichloromethane solution afforded unsaturated amide alkaloids 1a–1n. To the best of our knowledge, the synthesis of 1e and 1i was reported for the first time.Key words: synthesis, unsaturated amide alkaloids, Ramberg–Bäcklund reaction.