Stereoselective synthesis of multifunctionalized 1,2,4-triazolidines by a ruthenium porphyrin-catalyzed three-component coupling reaction

Abstract

Multifunctionalized 1,2,4-triazolidines have been synthesized by a ruthenium porphyrincatalyzed three-component coupling reaction. In a one-pot reaction, ruthenium porphyrins catalyzed the in situ generation of azomethine ylides from α-diazo esters and imines. Stereoselective 1,3-dipolar cycloaddition reactions of the azomethine ylides with dialkyl azodicarboxylates gave the corresponding 1,2,4-triazolidines in good yields (up to 85%). Using chiral 8-phenylmenthanol α-diazo ester as the carbenoid source, chiral 1,2,4-triazolidines have been obtained with good diastereoselectivity (up to 84% de). Some of the 1,2,4-triazolidines exhibited good cytotoxicity against human nasopharyngeal carcinoma (SUNE1) (IC50 = 10.4 μM) and human cervical carcinoma (Heia) (IC50 = 10.7 μM) cell lines. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.