Zinc(II) Triflate-Catalyzed Divergent Synthesis of Polyfunctionalized Pyrroles

The zinc(II) triflate-catalyzed synthesis of highly functionalized pyrroles is described. The sequence involves the preliminary preparation of alpha-aminohydrazones by Michael addition of primary amines to 1,2-diaza-1,3-dienes. The treatment of these intermediates with dialkyl acetylenedicarboxylates produces alpha-(N-enamino)-hydrazones that are converted into the corresponding pyrroles. The sub-stituents on the carbon in position four of 1,2-diaza-1,3-dienes drive the regioselectivity of the ring closure process. Starting from 4-aminocarbonyl-1,2-diaza-1,3-dienes only dialkyl 1-substituted 5-amino-carbonyl-1H-pyrrole-2,3-dicarboxylates are achieved by Lewis acid-catalyzed ring closure. A screening of several Lewis/Bronsted acid catalysts is performed. Zinc(II) triflate is the most efficient catalyst. Under similar reaction conditions, employing 4-alkoxycarbonyl-1,2-diaza-1,3-dienes, only 4-hydroxy-1H-pyrrole-2,3-dicarboxylates are synthesized. These latter reactions can be accomplished regioselectively also in one pot. Using 4-aminocarbonyl-1,2-diaza-1,3-dienes, diamines and dialkyl acetylenedicarboxylates the sequence provides the corresponding alpha,omega-di(N-pyrrolyl)alkanes.