2-Azidoazirines suitable for click chemistry: synthesis of 1-(2H-azirin-2-yl)-1H-1,2,3-triazoles

Abstract

2-Azidoazirines, sufficiently stable to be isolated in good yields, were synthesized by the cascade S_N2′–S_N2′ substitution of bromine in methyl 2-bromo-2H-azirine-2-carboxylates using sodium azide in acetonitrile. According to the DFT calculations, the first step, Br/N₃ exchange, is rate-determining and occurs in a concerted manner, while the subsequent N₃/N₃ exchange is a stepwise process. An alternative method using the TMSN₃/Et₃N/CH₂Cl₂ system permits the isolation in pure form of only 2-azidoazirines having an ortho-substituted aryl substituent at C3, although it is more efficient in a one-pot synthesis of 1-(azirin-2-yl)-1,2,3-triazoles from bromoazirines via the “cascade S_N2′–S_N2′ substitution/CuAAC reaction” sequence. The protocol has a broad scope for both azirines and alkynes and provides good product yields. The described CuAAC reaction of 2-azidoazirines represents the first example of a copper(I)-catalyzed reaction of azirines that occurs with the preservation of the azirine ring.