Fe(II)-Catalyzed Isomerization of 5-Chloroisoxazoles to 2H-Azirine-2-carbonyl Chlorides as a Key Stage in the Synthesis of Pyrazole–Nitrogen Heterocycle Dyads

Abstract

2-(1 H-Pyrazol-1-ylcarbonyl)-2 H-azirines were synthesized by in situ trapping of 2 H-azirine-2-carbonyl chlorides, generated by Fe(II)-catalyzed isomerization of 5-chloroisoxazoles, with pyrazoles. According to DFT calculations, the selectivity of nucleophilic substitution at the carbonyl group of 2 H-azirine-2-carbonyl chloride by a pyrazole nucleophile, which is a mixture of two tautomers, is controlled by thermodynamic factors. 2-(1 H-Pyrazol-1-ylcarbonyl)-2 H-azirines are excellent precursors for the preparation of two other pyrazole-nitrogen heterocycle dyads: 5-(1 H-pyrazol-1-yl)oxazoles by photolysis and 1-(1 H-pyrrol-2-ylcarbonyl)-1 H-pyrazoles by a Ni(II)-catalyzed reaction with 1,3-dicarbonyl compounds. 5-(1 H-Pyrazol-1-yl)oxazoles show strong emission in acetonitrile at 360-410 nm with high quantum yields.

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

“…Based on our experience of using isoxazoles in the synthesis of heterocyclic compounds [14][15][16][17][18], we hypothesized that isoxazoles 1 can undergo reductive ring opening under the action of Mo(CO) 6 /H 2 O/MeCN [14,[19][20][21][22][23] to enamines 3, which can be cyclized on acyl R 3 C(O) group to form pyridones 2 (Scheme 2, route a). The alternative cyclization scenario, which may involve the ester group of enamine 3 and lead to the formation of pyridone 5 (route b), is less likely due to the lower electrophilicity of the ester carbon compared to the acyl carbon.…”

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

“…Khlebnikov et al Synthesized 2‐(1 H ‐pyrazol‐1‐ylcarbonyl)‐2 H ‐azirines through in situ trapping of 2 H ‐azirine‐2‐carbonyl chlorides that arising from isomerization of 5‐chloroisoxazoles in the presence of a Fe (II) catalyst and pyrazoles. The selectivity of the nucleophilic reaction at the carbonyl group of the 2 H ‐azirine‐2‐carbonyl chloride with pyrazole was controlled by thermodynamic factors [102]. Another reactive heterocyclic building blocks, 2 H ‐Azirine‐2‐carbonyl azides were prepared in presence of sodium azide and 2 H ‐azirine‐2‐carbonyl chlorides in acetone through Fe(II)‐catalyzed isomerization of 5‐chloroisoxazoles [103].…”

Recent Trends in Iron‐Catalyzed Reactions towards the Synthesis of Nitrogen‐Containing Heterocycles

“…(a) Synthesis of azirines : The synthesis of 2‐(1 H ‐pyrazol‐1‐ylcarbonyl)‐2 H ‐azirines has been achieved by the trapping of 2 H ‐azirine‐2‐carbonyl chlorides in situ . Isomerization of 5‐chloroisoxazoles 1 with pyrazoles 2 in the presence of an iron(II) catalyst produces 2 H ‐azirine‐2‐carbonyl chlorides.…”