1,3-dipolar cycloadditions to levoglucosenone and related cyclic alkenes

Abstract

The cycloaddition of benzonitrile oxide to 2-alkoxy-5,6- dihyclro-2H-pyrans was investigated with particular interest in the factors affecting the regio- and stereoselectivity of the reaction. The 2-methoxy analogue showed weak activity and little selectivity. The isolated products consisted of two by-products, three 1:1 cycloadducts and three 2:1 cycloadducts. The -butoxy analogue afforded only two cycloadducts. Both arose from attack anti to the bulky alkoxy substituent. Addition of benzonitrile oxide and Q,j-dipheny1njtrone to a bridged pyran, 6,8-dioxabicyclo[3 .2. l]oct-3-ene, showed similar selectivity and much enhanced reactivity. Levoglucosenone, a chiral bicyclic enone showed excellent reactivity and selectivity in reaction with benzonitrile oxide. Two cycloadducts were isolated in a ratio of ca. 100:1 and a combined yield of 71%; the major adduct having added from the face anti to the methyleneoxy bridge. This isoxazoline was investigated further in reactions involving reduction of the carbonyl group, acetal formation and nucleophilic addition of nitromethane. Levoglucosenone was also shown to be a reactive dipolarophjle to other 1,3-dipoles such as nitrones, a nitrile imine and a carbohydrate nitrile oxide. The chemistry of some of these adducts was also investigated. Finally, the Michael addition of nitromethane to levoglucosenone was investigated under many different conditions and with different basic catalysts. The aim was to synthesise levoglucosenone with a primary nitro substituent to use as a nitrile oxide precursor. The series of reactions afforded 8 identifiable products, none of which was the desired Michael adduct.