The regiochemistry and stereochemistry of 1,3-dipolar cycloaddition of a cyclic nitrone

A study of the regiochemical and stereochemical behaviour of the 1,3-dipolar cycloaddition of a series of alkenes with 2,3,4,5-tetrahydropyridine 1-oxide has been carried out. The high degree of both regiochemical and stereochemical control observed in these reactions has been explained in terms of maximum overlap of frontier orbitals, repulsive steric encumbrance, and attractive secondary orbital interaction in the transition state. Most monosubstituted and 1,1-disubstituted alkenes gave 2-substituted cycloadducts. As the electron affinity of the monosubstituted alkene increases, an increasing tendency towards formation of the regioisomeric 3-substituted cycloadduct is encountered. 1,2-Disubstituted alkenes undergo cycloadditions to afford cycloadducts with electron-withdrawing substituents always in the C-3 position of the cycloadducts. Significant secondary orbital interaction is observed with the non-conjugated hydroxymethyl substituent.