Regioselective transformation of 6/5-fused bicyclic isoxazolidines to second-generation cyclic aldonitrones

Abstract

The cycloaddition reactions of 4-(2-hydroxy-2-propyl)-3,4,5,6-tetrahydropyridine 1-oxide with mono- and di-substituted alkenes have been found to be highly stereo- as well as face-selective. In solution, the 6/5 fused bicyclic cycloadducts remain solely as the cis-fused invertomers in order to accommodate the bulky tertiary substituent 2-hydroxy-2-propyl in the equatorial orientation. The cycloadducts, upon peracid oxidation, leads to the exclusive formation of synthetically important second-generation cyclic aldonitrones. The stereo- and face-selectivity of the cycloaddition reactions of these second-generation nitrones bearing substituents at C(4) and C(6) have been briefly examined. One interesting finding was that treatment of the first generation nitrone i.e., 4-(2-hydroxy-2-propyl)-3,4,5,6-tetrahydropyridine 1-oxide, with mercury(II) oxide afforded a novel bicyclic nitrone, 1-oxa-5,6-dehydro-6-azabicyclo[3,2,1]heptane 6-oxide.