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

A comparative study of the regio- and stereo-chemical behaviour of the 1,3-dipolar cycloaddition of a series of alkenes with 1-pyrroline 1-oxide and 2,3,4,5-tetrahydropyridine 1-oxide has been carried out. The high degree of both regio- and stereochemical control observed in these reactions has been explained in terms of frontier orbital interaction, steric factors, and secondary orbital interaction in the transition state. While most common alkenes (both mono- and 1,1-di-substituted) gave 2-substituted cycloadducts, highly polarized alkene dimethyl methylenemalonate afforded mainly regioisomeric 3-substituted cycloadduct. Significant secondary orbital interaction is observed with the non-conjugated substituents, hydroxymethyl and its derivatives.