Fragmentation of Cyclic Oximes to Alkynes Enabled by Anomeric Amides

Over the past few years, isodiazenes have reemerged as a powerful class of intermediates, with a vast synthetic potential. The most direct route to these reactive species is via reactions of N-nucleophiles with nitrenium ion precursors (i.e. anomeric amides). While emerging methodologies are almost exclusively based on amine-derived isodiazenes, analogous transformations based on other nitrogen functionalities (i.e. oximes, heterocycles) are vastly overlooked. Herein, we present a proof-of-principle that the reactivity of nitrenium ion precursors can be expanded beyond its current scope, supported by the development of an unprecedented reaction between anomeric amides and cyclic oximes – isoxazol-5-ones. This unorthodox transformation provides an operationally simple, scalable, and highly chemoselective route to challenging sterically hindered alkynes. Moreover, we demonstrate that anomeric amides can behave as surrogates of nitrous cation.