A simple one-pot procedure for the production of 2-carboxylpyrroles with 4-alkyl, 5-alkyl, 4aryl, 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 25-65% 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.
Procedure. -The Ti-catalyzed iminoamination reaction of alkynes, aniline or cyclohexylamine, and tert-butyl isocyanide produces 1,3-diimines, which are directly coupled with glycine ethyl ester hydrochloride to give 2-carboxypyrrole derivatives. The regioselectivity is controlled by the choice of the primary amine reactant aniline or cyclohexylamine and the nature of the starting alkyne. -(PASKO, C. M.; DISSANAYAKE, A. A.; BILLOW, B. S.; ODOM*, A. L.; Tetrahedron 72 (2016) 9, 1168-1176, http://dx.
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