Regioselectivity Associated with the 1,3-Dipolar Cycloaddition of Nitrones with Electron-Deficient Dipolarophiles

Article abstract of DOI:10.1021/jo00176a012

A study of the cycloaddition behavior of a series of electron-deficient dipolarophiles with C-aryl-N-alkylnitrones has been carried out.The 1,3-dipolar cycloaddition proceeds in high yield to produce isoxazolidines.This <3 + 2> cycloaddition embodies a high degree of both regiochemical and stereochemical control and provides an efficient entry into such heterocyclic systems.The reactions follow frontier orbital predictions.Most dipolarophiles undergo cycloaddition to give 5-substituted isoxazolidines.The orientation has been explained in terms of maximum orbital overlap of the nitrone LUMO-dipolarophile HOMO.As the electron affinity of the dipolarophile increases, an increasing tendency toward formation of the 4-substituted isoxazolidine is encountered.In certain cases diastereomeric isoxazolidines were formed via different two-plane orientation complexes.The ratio of the diastereomers reflects the free energy difference of the two transition states.This difference comes from repulsive interactions caused by steric hindrance and attractive van der Waal forces associated with maximum ? overlap of the substituent groups.The transition state which dominates in a particular case will depend on the nature of the groups attached to the N atom of the nitrone and to the dipolarophile ? bond.