2H-Azirine-2-carbonyl Azides: Preparation and Use as N-Heterocyclic Building Blocks

Abstract

2H-Azirine-2-carbonyl azides, new reactive heterocyclic building blocks, were synthesized in high yield by the reaction of sodium azide with 2H-azirine-2-carbonyl chlorides, generated by the Fe­(II)-catalyzed isomerization of 5-chloroisoxazoles. 2-(Azidocarbonyl)-1H-pyrroles, prepared by the Ni­(II)-catalyzed reaction of 2-(azidocarbonyl)-2H-azirines with 1,3-diketones, easily undergo the Curtius rearrangement in boiling tBuOH to give Boc-protected α-aminopyrroles in high yield. Heating of 2-(azidocarbonyl)-1H-pyrroles for a short time in inert solvents leads to the high-yield formation of benzo- and hetero-fused 1H-pyrrolo­[2,3-b]­pyridin-6­(7H)-ones, which are formed via a 6π electrocyclization involving the vicinal aryl or hetaryl substituent and the NC bond of isocyanate, generated by the Curtius rearrangement of the azidocarbonyl group. The Pd-catalyzed cross-coupling reaction of 1-acetyl-2-methyl-3H-pyrrolo­[2,3-c]­isoquinolin-5-yl triflate, easily prepared from the corresponding pyrroloisoquinolone, leads to variously 5-substituted 3H-pyrrolo­[2,3-c]­isoquinolines in excellent yields.

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

“…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]. Same group synthesized diazo‐containing azirines compound 2‐(diazoacetyl)‐2 H ‐azirines that involves the reaction of azirine‐2‐carbonyl chlorides with N ‐isocyano triphenyl iminophosphorane followed by treatment of the formed hydrazidoyl chloride with Et 3 N in the presence of TsCl as a catalyst (Scheme 81) [104].…”

Recent Advances for the Synthesis of N‐Unsubstituted Pyrroles

“…On the final stage of this domino sequence dehydration of C leads to formation of pyrroles 139 . The same group of authors [47] developed Ni(II)‐catalyzed reaction of substituted 2 H ‐azirine‐2‐carbonyl azides 144 with 1,3‐dicarbonyl compounds 20 for the synthesis of 2‐(azidocarbonyl)pyrroles 146 . Co(acac) 2 ‐catalyzed reaction of compounds 20 with 2‐(benzotriazole‐1‐ylcarbonyl)‐2H‐azirines 143 produced 2((benzotriazole‐1‐yl)carbonyl)pyrroles 145 in moderate to good yields (Scheme 49).…”

Nucleophile-Induced Rearrangement of 2H-Azirine-2-carbonyl Azides to 2-(1H-Tetrazol-1-yl)acetic Acid Derivatives

“…Rearrangements of 2 H -azirines with any substituents leading to heterocycles containing more than two nitrogen atoms are, to the best of our knowledge, still unknown . Recently the synthesis of 2 H -azirine-2-carbonyl azides was developed and used for the preparation of polyheterocycles . It was found that when azide 1a was heated in MeOH or tert -BuOH to obtain the corresponding azirin-2-ylcarbamate via Curtius rearrangement, it led to extensive tarring.…”

“…1 Recently the synthesis of 2H-azirine-2-carbonyl azides was developed and used for the preparation of polyheterocycles. 7 It was found that when azide 1a was heated in MeOH or tert-BuOH to obtain the corresponding azirin-2ylcarbamate via Curtius rearrangement, it led to extensive tarring. But recently by serendipity we found that 3-phenyl-2Hazirine-2-carbonyl azide 1a in MeOH at room temperature undergoes a quite unusual reaction leading to the formation of methyl 2-(5-phenyl-1H-tetrazol-1-yl)acetate 2a (59%) as the main product and azirine 3a (7%) as byproduct.…”