Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

Abstract

Summary3-Aryl-2H-azirines react with acylketenes, generated by thermolysis of 5-arylfuran-2,3-diones, to give bridged 5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene-2,10-diones and/or ortho-fused 6,6a,12,12a-tetrahydrobis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine-4,10-diones. The latter compounds, with a new heterocyclic skeleton, are the result of the coupling of two molecules of azirine and two molecules of acylketene and can be prepared only from 3-aryl-2H-azirines having no electron-withdrawing groups in the aryl substituent. Calculations at the DFT B3LYP/6-31G(d) level for the various routes of bis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine skeleton formation revealed a new domino reaction of 3-aryl-2H-azirines occurring in the presence of furandiones: acid-catalyzed dimerization to dihydropyrazine followed by consecutive cycloaddition of the latter to two molecules of acylketenes.

Catalyst-free formal [4+1]/[4+2] cyclization cascade sequence of isocyanides with two molecules of acylketene formed in situ from thermal-induced Wolff rearrangement of 2-diazo-1,3-diketones

“…Based on the aforementioned results and previous reports [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][57][58][59], a possible reaction mechanism was proposed in Scheme 4. Initially, the thermal-induced decomposition of 2diazo-1,3-diketone 2 leads to the formation of acylketene intermediate Int-I by Wolff rearrangement, followed by the intermolecular nucleophilic attack of isocyanides 1 yielding the highly reactive nitrilium ion intermediate Int-II.…”

“…In most cases, these reactions give rise to products of formal [4+1] [38][39][40][41][42][43] or [4+2] [44][45][46][47] cycloaddition. In particular, reactions of acylketenes with the C@N double bond of imines leads to derivatives of 1,3-oxazines [48][49][50]. Whereas cascade [4+1]/[4+2] reactions of isocyanides with two molecules of acylketenes leading to O,O,N-spiro compounds are rarely explored.…”

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

“…To the best of our knowledge, neither heterocyclic systems with a 4,6-dioxa-1-azabicyclo[3.2.1]oct-2-ene backbone (compounds 6 ) nor systems with a 5,7-dioxa-1-azabicylo[4.4.1]undec-8-ene backbone (compounds 7 ) have ever been reported. On the contrary, bicyclic compounds 8f , g are representatives of a known class of 5,7-dioxa-1-azabicylo[4.4.1]undeca-3,8-diene-2,10-dione derivatives formed by the recently reported reaction of 3-arylazirines with acyl ketenes generated by thermolysis of 2-diazo-1,3-diketones [ 12 ] or 5-arylfuran-2,3-diones [ 13 ]. Therefore, the presence of compounds 8f , g among the reaction products provides evidence for the formation of some amounts of acetyl(methyl)ketene ( 12 ) under the reaction conditions, which, in turn, gives us insight to the mechanism of formation of adducts 6 and 7 ( Scheme 3 ).…”

“…In these syntheses 2 H -azirines serve as C–C–N three-atomic building blocks for the construction of both acyclic compounds, such as nonproteinogenic amino acids and peptides [ 1 – 3 ], and various 4–7-membered heterocycles [ 4 – 11 ]. The reactions of azirines with acylketenes [ 12 – 13 ], carboxylic acids [ 14 ] and amino acids [ 1 ] proceed via N–C3 bond cleavage to afford 5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene derivatives, ketamides, and aminoamides, respectively. On the other hand, rhodium carbenoids derived from α-diazocarbonyl compounds transform 2 H -azirines 1 to azirinium ylides 5 ( Scheme 1 ) which undergo facile N–C2 bond cleavage to give 2-azabuta-1,3-dienes 3 .…”

Synthesis of 2,3-Dihydro-1,3-oxazin-4-ones via a Mild Formal [4+2] Cycloaddition of Acylketenes with Aldimines

“…5 To date, there have been only a limited number of approaches for the preparation of 1,3-oxazinones and their derivatives. Traditionally, 1,3-oxazin-4-ones are prepared through the reaction of aldimines and reagents such as diketene, 6 dioxinone, 7 acyl Meldrum's acid, 8 α-diazo-β-dicarbonyl, 9 and furan-2,3-dione 10 as acylketene surrogates under thermal or photoirradiation conditions. The modest yields of these reactions coupled with the toxicity, complexity, and the inherent high reactivity of such reagents, limit the utility of many of these reported approaches.…”