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

A synthesis of 2-diazoacetyl-2 H-azirines was developed starting from 2 H-azirine-2-carbonyl chlorides, generated by Fe(II)-catalyzed isomerization of 5-chloroisoxazoles. 2-Diazoacetyl-2 H-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-2 H-azirin-2-yl)-2-halo- and 2-(R-oxy)ethan-1-ones in good yields. The synthesized 2 H-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-2 H-azirine, and 2-diazoacetylaziridine derivatives.