Reactivity, regiochemistry, and stereochemistry of a cyclic nitrone and its α-keto derivative in 1, 3-dipolar cycloaddition reactions

Rate constants for the cycloadditions of 3,4,5,6-tetrahydropyridine 1-oxide (1), and 3-oxo-3,4,5,6-tetrahydropyridine 1-oxide (2) to several mono- and disubstituted alkenes have been determined at 36°C by ¹H NMR Spectroscopy. Small solvent effect on the rate constant indicate the concerted nature of the reaction. It is found that nitrone 2 reacts slower than 1 because of the presence of bond opposition strain in the transition state for the former nitrone. Addition rates are influenced by the dipole moments of the nitrones. Reactivity of these addition reactions usually follows the prediction of frontier orbital approximation. Both the nitrones exhibit very similar regiochemical and stereochemical properties. Significant secondary orbital interaction is observed with several electron deficient alkenes. However, maleic anhydride is found to undergo addition predominantly via exo mode of attack.