Copper catalyzed aerobic oxidation of hydroxamic acids to acylnitroso compounds and their trapping

Abstract

A novel in situ oxidation of hydroxamic acids to form the corresponding nitroso species using a copper-oxazoline complex in air was developed. The nitroso species could be trapped by a diene to give high yields of Diels-Alder adducts, with some competing ene-products with certain dienes. It was found that 10 mol% CuCl2 and 20 mol% 2-ethyl-2-oxazoline in methanol under air were optimal conditions for catalyzing the oxidation of N-(benzyloxycarbonyl)hydroxylamine, for example, which was then trapped with various dienes to form the corresponding cycloadducts in good yields. However, this catalytic system will only works with hydroxamic acids with a heteroatom between the aryl and carbonyl group of the hydroxamic acid. It was also found that oxidation 1-hydroxy-3-phenylurea using this Cu-based oxidation system gave the best regio- and chemo-selectivity, though attempts to induce high asymmetric induction on the NDA reaction using both chiral catalysts and auxiliary approaches were unsuccessful which has implications about the rate of dissociation of the nitroso species of the copper oxidant.