Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• chlorides have been developed. Keywords: azirine-2,2-dicarboxamides; azirine-2,2-dicarboxylic acids; isomerization; isoxazoles; Introduction The isomerization of isoxazoles, containing a heteroatomic substituent at C5, to 2H-azirines is a powerful method for the preparation of 2H-azirine-2-carboxylic acid

• -ylcarbonyl)-2H-azirines, 1-(2H-azirine-2-carbonyl)benzotriazoles, 2H-azirine-2-carbonyl azides, anhydrides, amides, esters, and thioesters of azirine carboxylic acids, as well as azirine carboxylic acids themselves, have been prepared over the last decade (see [2] and references therein). Azirine-2

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• utility of their reaction, the authors studied the one-pot conversion of the vinyl azides to 2H-azirines 161. The carboazidation reaction for the aryl alkynes was completed in a comparable amount of time. A myriad of different functionalized π-systems was tolerated by the reaction, demonstrating its

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• ][4][5][6][7][8][9][10][11][12][13]. Pyrroles with vicinal o-bromophenyl and heteroaryl substituents, which are readily accessible via reactions of the corresponding 2H-azirines and phenacylcycloiminium ylides [14][15][16][17][18][19], are excellent precursors for various fused aza-heteroaromatics via

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• preparation of 2H-azirines and their stereoselective transformation into highly functionalized NH-aziridines, starting from vinyl azides and organolithium compounds. The protocol has been developed using cyclopentyl methyl ether (CPME) as an environmentally benign solvent, resulting into a sustainable, safe

• and potentially automatable method for the synthesis of interesting strained compounds. Keywords: aziridines; 2H-azirines; flow chemistry; green chemistry; organolithium compounds; Introduction Since their conception in the early 1990s, Green Chemistry Principles (GCP) have been applied with

• olefins [13][14]. Aziridines are otherwise accessible from a variety of acyclic precursors [15][16][17], even stereoselectively [18][19][20], and through derivatization of 2H-azirines. The reactions using 2H-azirines as electrophiles proceed with several nitrogen, oxygen and sulfur nucleophiles, enabling

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• release approach, the Xiao group reported a synthesis of the pyrroles 35.3 in 2014 [153]. They can be accessed via a photocatalytic formal [3 + 2] cycloaddition of the 2H-azirines 35.1 and the alkynes 35.2 (Scheme 35). The use of Mes-Acr-Me+ (OD2) was successful due to its high reduction potential in the

• excited state, together with an intense absorption in the visible-light region. The transformation proceeds via the single-electron oxidation of 2H-azirines, forming a nitrogen-centered radical cation, which is prone to ring opening. The driving force of the ring strain release and irreversible ring

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• the [3 + 2]-cycloaddition of electron-poor alkynes and 2H-azirines [60]. The reaction is performed under blue LED irradiation and using acridinium salts as a photocatalyst (Scheme 15). With respect to 2H-azirine the scope of the reaction is demonstrated to be relatively broad, with aromatics

• ). The reaction uses 2H-azirines and aldehydes to access the functionalised heterocycles [61]. Unlike the pyrrole-forming reaction, this protocol requires an oxidising agent, DDQ, for the desired oxazole to be obtained. This means that access to the corresponding 2,5-oxazolines is also possible

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• (Tianjin), Tianjin 300072, China 10.3762/bjoc.14.123 Abstract The reaction of enamine compounds with the Togni reagent in the presence of CuI afforded β-trifluoromethylated enamine intermediates, which were converted directly to biologically interesting trifluoromethylated 2H-azirines by an iodosobenzene

• potential anti-HIV drug bearing a NCF3 moiety. 2H-Azirines are a class of highly strained and reactive molecules containing a C–N double bond. The exclusive framework can be found in some natural products [43][44][45][46][47], which were shown to possess antibiotic activities [43][44]. Furthermore

• ) [56][57]. When the R2 substituent is alkyl or aryl, the corresponding substrates 2 were converted to a series of alkylated or arylated 2H-azirines 3 in the presence of phenyliodine diacetate (PIDA) in 1,2-dichloroethane (DCE) [56]. Alternatively, the treatment of β-unsubstituted enamine substrates (2

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• temperature, it affords highly substituted 2-(trifluoromethyl)oxazoles. These flexible transformations proceed under solvent free conditions in good to excellent yields without any catalyst. Keywords: α-amido-1,3-diketones; α-azidochalcones; carboxylic acids; 2H-azirines; oxazoles; Introduction α

• reactive intermediate in several synthetic transformations [10][11][12][13][14][15]. The chemistry of 2H-azirines has been extensively explored because of its strained molecular structure, unique reactivity and synthetic applications [10][11][12][13][14][15][16][17][18][19][20][21][22]. α-Substituted 2H

• character of the C(2)–N double bond is higher than a normal imine (Figure 1) [10][26][27]. The generated substituted aziridines A2 may undergo further ring opening reactions. The α-azidochalcones 1 are suitable as precursors for the generation of 2H-azirines A1, though several other methods are available

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• -imidazoles based on the formation of a pyrrole ring via the reaction of 2H-azirines with 1-alkyl-3-phenacyl-1H-imidazolium bromides [29], in which one example of the synthesis of ethyl 4-imidazolylpyrrole-2-carboxylate from ethyl 3-methyl-2H-azirine-2-carboxylate was described. Earlier it was found that

• according to Scheme 2, whereby excluding the isolation of often unstable 2H-azirines [34]. Results and Discussion The synthetic scheme (Scheme 2) implies an implementation of all stages (1: generation of azirine 8 from isoxazole 7 under FeCl2 catalysis; 2: formation of phenacylimidazolium ylide 10 induced

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

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• , Universitetskaya nab. 7–9, 199034 St. Petersburg, Russia 10.3762/bjoc.11.35 Abstract Strained azirinium ylides derived from 2H-azirines and α-diazoketones under Rh(II)-catalysis can undergo either irreversible ring opening across the N–C2 bond to 2-azabuta-1,3-dienes that further cyclize to 2H-1,4-oxazines or

• reversibly undergo a 1,5-cyclization to dihydroazireno[2,1-b]oxazoles. Dihydroazireno[2,1-b]oxazoles derived from 3-aryl-2H-azirines and 3-diazoacetylacetone or ethyl diazoacetoacetate are able to cycloadd to acetyl(methyl)ketene generated from 3-diazoacetylacetone under Rh(II) catalysis to give 4,6-dioxa-1

• ; Introduction 2H-Azirines are unique strained compounds which have found various applications in organic synthesis due to their ability to react both with retention and opening of the three-membered ring. Even though each of the three bonds in the azirine ring can be cleaved under certain conditions, the

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• synthetic approach to derivatives of 2H-1,3-oxazines via a Rh2(OAc)4-catalyzed reaction of diazo esters with 2-acyl-2H-azirines F. This reaction involves the intermediate formation of azirinium ylides G, their transformation into 1-oxa-5-azahexa-1,3,5-triene D, and finally the 6π-electrocyclization of the

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

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• 10.3762/bjoc.10.74 Abstract 3-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. Keywords

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• Stephan Cludius-Brandt Lukas Kupracz Andreas Kirschning Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany 10.3762/bjoc.9.201 Abstract The photodenitrogenation of vinyl azides to 2H-azirines by using a photoflow reactor is reported and compared

• with thermal formation of 2H-azirines. Photochemically, the ring of the 2H-azirines was opened to yield the nitrile ylides, which underwent a [3 + 2]-cycloaddition with 1,3-dipolarophiles. When diisopropyl azodicarboxylate serves as the dipolarophile, 1,3,4-triazoles become directly accessible starting

• cycloaddition reactions. They are commonly formed through three routes which are a) the addition of electrophilic carbenes to nitriles, b) the dehydrochlorination of imidoyl chlorides, and c) the photochemical ring opening of strained 2H-azirines 2 [2][3][4][5]. The latter route can be initiated by the

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• , vinyl azides can be converted into the corresponding 2H-azirines by thermolysis or alternatively by photolysis [5]. The highly reactive azirines can further react as dipolarophiles, dienophiles, electrophiles or nucleophiles [6] thereby accessing oxazoles and isoxazoles [7]. In addition, 2H-azirines