Facile access to 2-acyloxy-, aryloxy- and alkenyloxy-2H-azirinesviaan S_N2′–S_N2′ cascade in 2-halo-2H-azirines

Abstract

Various 2-oxygen-substituted 2H-azirine-2-carboxylic acid derivatives were synthesized in high yields under mild conditions from readily available precursors, 2-halo-2H-azirines and OH-reagents having pKa values in the range of 3-10. This reaction is the first example of substitution at the azirine carbon atom for which an unusual SN2'-SN2' cascade mechanism was revealed.

Easy Access to 2-Fluoro- and 2-Iodo-2H-azirines via the Halex Reaction

“…Taking into account the results of the calculations and experimental data obtained for the halogen substitutions in 2-halo-2H-azirine-2-carboxylates with O-and N-nucleophiles, 10,19 we believe that the halogen exchange reactions described above also proceed via a cascade S N 2′-S N 2′ mechanism.…”

“…Thus, aliphatic and aromatic carboxylic acids react with methyl 2-bromo-3-phenyl-2H-azirine-2-carboxylate (1a) in the presence of Et 3 N to afford 2-acyloxy derivatives in high yields, while with substantially more acidic trichloroacetic acid the reaction does not occur. 10 As far as we know, there is no information in the literature on the use of halide ions as nucleophiles in such reactions.…”

“…The latter was chosen because of its synthetic accessibility and high reactivity in the substitution reactions. 10,19 It was found that 1a reacted with tetrabutylammonium fluoride hydrate (TBAF•H 2 O) in toluene at ambient temperature to afford the target fluoride 2a in good yield ( Table 1, entry 1). Screening of other sources of fluoride ion and solvents (entries 2-6) showed that the highest yield of fluoride 2a from bromide 1a was achieved using TBAF•H 2 O (1.3 equiv) in dichloromethane (DCM) at room temperature (entry 2).…”

“…Besides, 2-iodo-2H-azirines are much more reactive in substitution reactions than 2-bromoazirines, and there are cases when less accessible iodides cannot be replaced by more accessible bromides. 10 The known methods for the synthesis of these compounds are based on two strategies. In the framework of the first strategy, the 2-haloazirine ring is formed through the cyclization of halogenated open-chain precursor, for example, through thermal cyclization of a 2-halovinylazide.…”

Synthesis of various functionalized 2H‐azirines: An updated library

“…The reaction is carried out at room temperature and provides high yields of carboxylic acids, enols, and phenols with pKa values in the range of 3–10. This method can be successfully used to synthesize compounds containing two azirine groups in the same molecule (Schemes 113 and 114) [133].…”