Regioselective Functionalization. 5. Nitrogen Insertion Reactions of Bicyclooctan-2-one. Reexamination of Bridgehead vs. Methylene Migratory Preferences

Article abstract of DOI:10.1021/jo00346a001

Earlier reports of totally regioselective bridgehead nitrogen insertion upon rearrangement of the oxime of bicyclo<3.2.1>octan-2-one (1), by using benzenesulfonyl chloride/sodium hydroxide as a Beckman catalyst, but completely regioselective methylene migration upon reaction of ketone 1 with hydroxylamine hydrogen sulfate in sulfuric acid have been found to be inaccurate.Lactams 3, formed by bridgehead migration, and 4, arising from methylene migration, are afforded under both sets of reaction conditions as shown by 1H and 13C NMR analyses of crude reaction mixtures.Upon examination of a number of nitrogen insertion reaction conditions, the most regioselective formation of bridgehead nitrogen insertion product 3 (95percent) can be effected by reacting ketone 1 with hydroxylamine-O-sulfonic acid in formic acid.The preference for nitrogen insertion adjacent to methylene was highest for reaction of ketone 1 with hydroxylamine hydrochloride/sulfuric acid which gave a 69percent preference for lactam 4.This exceeds the methylene migratory preference for the Schmidt reaction of ketone 1 with hydrazoic acid, which gives 62percent lactam 4.