From Azirinyl Radicals to Azirinium Cations: Small-Ring N-Heterocyclic Reactive Intermediates

Late-stage functionalization via reactive intermediates has recently emerged as an efficient way to access structurally diverse small rings, as illustrated with cyclopropyl radicals or cyclopropenium cations, which have opened valuable new synthetic opportunities. Their nitrogen counterparts, however, remain underexplored despite the importance of heterocycles in synthetic and medicinal chemistry. Herein, we demonstrate that azirinyl radicals and azirinium cations can be reliably accessed from a common N-hydroxyphthalimide ester azirine precursor under blue light irradiation, without the need for a metal catalyst. Under reductive conditions, azirinyl radicals can be added to electron-poor alkenes and using a radical polar-crossover approach, azirinium cations can be trapped with nucleophiles. Both pathways are high-yielding, chemically robust and scalable to give azirines with a wide range of substituents previously inaccessible and can be applied to complex drug-derived molecules. The obtained azirines could be converted to the corresponding aziridines diastereoselectively.