Two stereoisomers of butenedioic acid-mediated synthesis of tetrahydropyridine carboxylate derivatives with the same stereochemistry

Abstract

Fumaric and maleic acids are utilized as two environmental-friendly and efficient catalysts for a one-pot, pseudo five-component coupling reaction, containing aromatic amines, aromatic aldehydes and methyl acetoacetate/ethyl acetoacetate. In this work, a variety of differently substituted aldehydes and amines were tolerated very well, affording cyclic compounds with two consecutive stereogenic centers in moderate to high yields and with excellent diastereoselectivities. In this research, the catalytic effect of maleic acid is compared with that of fumaric acid. According to the obtained results in the presence of both of them, products were produced with the same streochemistry. These reactions were performed under mild conditions to yield 1,2,5,6-tetrahydropyridine-3-carboxylate derivatives with good to excellent yields (46–91%). When fumaric acid was used instead of maleic acid as catalyst the yields of products were relatively low. This is probably because of the stereochemistry of fumaric acid. The main benefits of this process are the easy work-up, short reaction times, green catalysts and no chromatographic purifications. The work-up of these reactions involves only a filtration and a simple washing step with EtOH, and there is no need for column chromatography.