One-pot synthesis of pyrroles using a titanium-catalyzed multicomponent coupling procedure

Abstract A simple one-pot procedure for the production of 2-carboxylpyrroles with 4-alkyl, 5-alkyl, 4-aryl, 4-aryl-5-alkyl, or 3,4-diaryl substitution patterns is presented. The procedure involves the titanium-catalyzed multicomponent coupling of alkynes, primary amines and isonitriles to give 1,3-diimines in situ; the multicomponent product is then treated with the ethyl ester of glycine hydrochloride to give the NH -pyrrole. The reaction can be carried out with the neutralized glycine ester or with the hydrochloride salt using DBU as a base. Yields of pyrrole based on starting alkyne varied from 25 to 65% over the one pot procedure, and in most cases only one regioisomer of the product is observed. Further, it is proposed that the regioselectivities of the reactions are a result of rate-determining ring closure after relatively fast transimination with glycine ethyl ester.