2‑Diazoacetyl‑2H‑azirines: Source of a Variety of 2H‑Azirine Building Blocks with Orthogonal and Domino Reactivity

A synthesis of 2-diazoacetyl-2H-azirines was developed starting from 2H-azirine-2-carbonyl chlorides, generated by Fe­(II)-catalyzed isomerization of 5-chloroisoxazoles. 2-Diazoacetyl-2H-azirines easily undergo reactions characteristic of α-diazo ketones with preservation of the azirine ring. Reactions with hydrohalogenic, carboxylic, and p-toluenesulfonic acids provide novel 1-(3-aryl-2H-azirin-2-yl)-2-halo- and 2-(R-oxy)­ethan-1-ones in good yields. The synthesized 2H-azirines can offer many possibilities for chemical manipulation in heterocyclic synthesis, due to the presence of highly reactive azirine and the exocyclic C­(O)–CHN2 or C­(O)–CH2X functionalities, which can show orthogonal or domino reactivity. The synthetic usefulness of the developed building blocks was demonstrated by the preparation of new types of heterocyclic dyads (azirine–oxazole, azirine–pyrazoline, azirine–thiazole, azirine–oxirane, pyrrole–oxazole) as well as an azirine chalcone analogue, 2-azidoacetyl-2H-azirine, and 2-diazoacetylaziridine derivatives.