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

• developed protocol doesn’t require column chromatography for purification of target compounds 3 and can be performed in a gram scale. Pyridinium bromides 1a–l,n–w and iodide 1m were prepared by the reaction of 3-(2-bromophenyl)-2H-azirine (4a) with substituted N-phenacyl pyridinium salts 5a–w according to

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

• , 3-(o-tolyl)-2H-azirine (2d) and 2,3-diphenyl-2H-azirine (2l) were also obtained in excellent yields. When 1-(1-azidovinyl)-2,3,4,5,6-pentafluorobenzene (1k) was reacted under optimal flow conditions, a mixture of 1k and 2H-azirine 2k (20:80 ratio) was recovered. Unfortunately, it was not possible to

• isolate 3-(perfluorophenyl)-2H-azirine (2k) due to its rapid polymerization in the crude mixture. Interestingly, aliphatic vinyl azides 1h–j were found less reactive, and the corresponding azirines 2h–j were obtained in just 74–77% yield, in mixtures with unreacted starting materials. However, when the

• good yields. Subsequently, other vinyl azides were tested for this flow-batch two-step procedure (Scheme 3). Starting from vinyl azide 1d, the corresponding 3-(o-tolyl)-2H-azirine (2d) was generated under flow conditions, and reacted with PhLi, HexLi and BuLi, furnishing NH-azirdines 3e–g. Aliphatic

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• 058, India Department of Inorganic and Physical Chemistry, Indian Institute of Science (IISc), Bangalore-560 012, India 10.3762/bjoc.16.178 Abstract The reactivity of α-azidochalcones has been explored for the preparation of highly substituted oxazoles via a 2H-azirine intermediate. The

• ; potassium persulfate; thiazole; vinyl azide; Introduction Vinyl azide is one of the most versatile and potent building blocks explored in the synthesis of several heterocycles [1][2][3][4][5]. It can undergo photolysis or thermolysis to afford highly strained three-membered 2H-azirine, which can act as the

• ][41][42]. 2,4,5-Trisubstituted oxazoles are embedded in some natural products and pharmaceuticals with a broad range of biological activities prompting the development of efficient synthetic strategies for this useful heterocycle [43][44] (Figure 1). In the recent past, the readily accessible 2H

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

• . Aliphatic and heteroaromatic substituents on the 2H-azirine were not tolerated. The aldehyde substituents are much more diverse, with a variety of substituted benzenes, heteroaromatics, carbonyls and aliphatic side chains undergoing the cycloaddition. Overall, these two methods provide much more mild

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

• (PhIO)-mediated intramolecular azirination in a one-pot process. Keywords: azirination; 2H-azirine; iodosobenzene; Togni reagent; β-trifluoromethylation; Introduction The trifluoromethyl group is a striking structural motif, which can be widely found in the fields of pharmaceutical and agrochemical

• [52][53][54][55] have been developed for accessing this exclusive class of heterocycles. In our previous works, we have realized the application of hypervalent iodine reagents for the construction of the 2H-azirine skeleton starting from enamines 2 via intramolecular oxidative cyclization (Scheme 1

• , R2 = H) with PhIO in 2,2,2-trifluoroethanol (TFE) afforded 2-trifluoroethoxy-2H-azirines 4 [57]. The latter process involves an intermolecular oxidative trifluoroethoxylation and the subsequent oxidative intramolecular azirination. In continuation of our interest in the construction of the 2H-azirine

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

• Abstract The reaction of α-azidochalcones with carboxylic acids has been investigated resulting in the formation of α-amido-1,3-diketones under microwave irradiation via in situ formation of 2H-azirine intermediates. An interesting reaction is described wherein, with trifluoroacetic acid at lower

• -azirines are impressive intermediates for the synthesis of various substituted heterocyclic compounds [23][24][25]. Nucleophiles can interact with the electrophilic carbon of the strained 2H-azirine rings and due to the ring strain in the three-membered 2H-azirine ring system A1, the electrophilic

• (Figure 2) [10][24]. In this article, we intend to demonstrate the reactivity of 2H-azirine A1 towards carboxylic acids [28]. α-Azidochalcones have been chosen to generate 2H-azirines via vinyl nitrene intermediates. α-Azidochalcones can be synthesized from the corresponding benzylidene acetophenones in

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

• alkyl 2H-azirine-2-carboxylates can be prepared by isomerization of 5-alkoxyisoxazoles under Fe(II)-salt catalysis [30]. Quite recently this isomerization has been used for the preparation of substituted pyrrole-2-carboxylic acid derivatives by the domino reaction of 3-aryl-5-methoxyisoxazoles with 1,3

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

• at all. Our study of the chemical behavior of 2H-azirines under Rh(II)-catalyzed decomposition of diazoketones was started with searching for optimal conditions for the catalytic reaction of 2,3-diphenyl-2H-azirine (1a) with 1-diazo-1-phenylpropan-2-one (2a), leading to oxazine 4a. The most

• characterized by standard spectral methods and the structures of adducts 6f and 7h were additionally confirmed by X-ray diffraction analysis (Figure 2). The reaction of diazoacetylacetone 2c with 2,3-diphenyl-2H-azirine (1a) provides oxazine 4i as a sole product (Table 1, entry 10). It was isolated with the

• depends on the electronic effects of the para substituents in the aryl group of 3-aryl-2H-azirine 1. The [3.2.1] adduct is preferably formed from azirines 1e,f with electron-donating substituents (Table 1, entries 7 and 8), while 3-(4-nitrophenyl)-2H-azirine (1g) provides the [4.3.1] adduct only (Table 1

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

• . The analytical and isolated yields of the reaction products are listed in Table 2. Compounds 3–5 were fully characterized using standard spectral methods. The structures of compounds 3а, 4b were confirmed by X-ray analysis (Figure 1). Furandiones 1a–c react with 3-(4-nitrophenyl)-2H-azirine (2c) to

• -azirine leads to an increase of yield of 1:2 adduct 3, and in the case of 3-(4-nitrophenyl)-2H-azirine (2c) it becomes the only product, while from 3-(4-methoxyphenyl)-2H-azirine (2b) only 2:2 adducts 4 and 5 were formed. It is also worth noting that in all cases the proportion of cis-isomer 4 was larger

• to an increase in the yield of 1:2 adduct 3, and in the case of 3-(4-nitrophenyl)-2H-azirine (2c) it becomes the only product, while from 3-(4-methoxyphenyl)-2H-azirine (2b) only 2:2 adducts 4 and 5 were formed. Calculations at the DFT B3LYP/6-31G(d) level for various routes of bis[1,3]oxazino[3,2-a

[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

• pyrex filter. Test reactions conducted either in benzene or in toluene resulted exclusively in the formation of the corresponding 2H-azirine 2a in yields up to 95%, while no formation of the cycloaddition product was encountered (Table 2; entries 1 and 2). 2a could easily be identified by the signal at

Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

• Farhan R. Bou-Hamdan,
• François Lévesque,
• Alexander G. O'Brien and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2011, 7, 1124–1129, doi:10.3762/bjoc.7.129

• expansion of 12, via 2H-azirine 3, affords didehydroazepine 4, which can be trapped by variety of nucleophiles to provide the corresponding azepine 5. Alternatively, intersystem crossing (ISC) of 12 gives rise to 32, which can dimerize to form diazo compound 6. Performing the reaction in the presence of