Chemoselectivity of [4 + 2] cycloaddition in N-maleyl- and N-allyl-2,6-difurylpiperidin-4-ones

Abstract

On the basis of a transition state conformation analysis, an attempt was made to explain the high chemoselectivity of intramolecular [4 + 2] cycloaddition in 3-alkyl-2,6-difuryl-N-maleylpiperidin-4-ones. It was shown that the thermal Diels–Alder reaction in these piperidine derivatives takes place through the “boat” conformation and leads to the formation of hydrogenated 1-alkyl-4-(2-furyl)-2H-8,10a-epoxy-pyrido[2,1-a]isoindol-2-ones. The alternative regioisomers, 3-alkyl-4-(2-furyl)-2H-8,10a-epoxy-pyrido[2,1-a]isoindol-2-ones, are hardly formed at all. At the same time, the intramolecular Diels–Alder reaction in the isostructural 3-alkyl-N-allyl-2,6-difurylpiperidin-4-ones, takes place non-regioselectively from the “chair” conformation.