REVERSING THE REGIOCHEMICAL COURSE OF 1,3-DIPOLAR CYCLOADDITION OF NITRILE OXIDES BY MODIFICATION OF DIPOLAROPHILES

The orientation of the cycloaddition of nitrile oxide to beta-substitu ted-alpha,beta-unsaturated aldehyde equivalents was directed by choice of the carbonyl protective group; both of the two possible regioisome rs of 2-isoxazolines were selectively prepared. Cycloaddition to the a cetal derivatives preferentially gave the regioisomer bearing acetal g roup on C(4) position. While the opposite regioselectivity was observe d for the cycloaddition to dithioacetal derivatives, where the sulfur functional group was mainly located at C(5) position. Theoretical stud ies on these regiochemical courses showed the C(5) orientation of dith ioacetal groups to be directed by steric control, whereas frontier orb ital interaction controlled the C(4) orientation of the acetal groups.