Synthesis of Pyrroles from Allenic Aldehydes and Amines

Significance

Sulfanyl-substituted allenic aldehydes undergo acid-catalyzed reaction with amines to afford pyrrole derivatives in modest to good yields. The allenic aldehydes are available in a three-step sequence starting with diazoacetates and propargyl sulfides. Although substituent variation in the allenyl aldehyde was insufficiently explored, the reaction provides considerable scope for the construction of highly substituted pyrroles. Two mechanistic pathways are suggested which differ in the manner of 1,2-migration of the sulfanyl group. Both start with the generation of the imine intermediate which undergoes intramolecular cyclization and elimination of the sulfanyl group. In path A, sequential attack of the released sulfanyl group at the iminium carbon and rearomatization leads to the pyrrole product. Path B involves a nucleophilic attack of the imine by the sulfur group and a simultaneous attack of the allene by the nitrogen atom to generate a thiirenium species which then undergoes ring opening and further deprotonation to afford the product.