Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• features a broad substrate scope, simple reaction conditions, and high molecular convergence. Keywords: acylhydrazone; annulation; azepine; MBH carbonate; spirooxindole; Introduction Among the various N-containing heterocyclic compounds, 1,2-diazepine represents one of the important privileged structural

• efficient synthesis of spiro[azepine-4,3'-indoline] derivatives via the [4 + 3] cycloaddition reaction of bromo-substituted isatin-derived MBH adducts and N-(o-chloromethyl)arylamides. In this efficient protocol, the reactive allylic phosphonium ylides and aza-o-quinone methides were generated in situ and

• satisfactory yields and with good diastereoselectivity (reaction 3, Scheme 1) [57]. Very recently, we found that the base-catalyzed [4 + 3] cycloaddition reaction of isatin-derived MBH carbonates with various α,β-unsaturated N-arylaldimines affords spiro[indoline-3,5'-pyrrolo[3,4-b]azepine] derivatives

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• reaction [39]. Recently, An and co-workers reported a helical, azepine-containing NG 27 by the introduction of an NH in the seco-HBC framwork (Scheme 3). Single-crystal X-ray diffractometry revealed the mixed P/M enantiomers. Taking advantage of the grafting NH functional group, the optical resolution of

• ]azepine and tetrabromothiophene-S,S-dioxide, followed by oxidative aromatization in the presence DDQ to afford compound 25 in an overall 75% yield. Suzuki−Miyaura cross-coupling reaction of compound 25 with (4-ethylphenyl)boronic acid in the presence of Pd(CH3CN)2Cl2, SPhos, and K3PO4 then furnished the

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• David I. H. Maier Barend C. B. Bezuidenhoudt Charlene Marais Department of Chemistry, University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa 10.3762/bjoc.19.51 Abstract The dibenzo[b,f]azepine skeleton is important in the pharmaceutical industry, not only in terms of existing

• commercial antidepressants, anxiolytics and anticonvulsants, but also in reengineering for other applications. More recently, the potential of the dibenzo[b,f]azepine moiety in organic light emitting diodes and dye-sensitized solar cell dyes has been recognised, while catalysts and molecular organic

• frameworks with dibenzo[b,f]azepine derived ligands have also been reported. This review provides a brief overview of the different synthetic strategies to dibenzo[b,f]azepines and other dibenzo[b,f]heteropines. Keywords: dibenzo[b,f]azepine; dibenzo[b,f]heteropine; dibenzo[b,f]oxepine; iminostilbene

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• ]. Functionalization of the phenyl ring in the benzophenone gives rise to an additional axial chirality (L3), thus improving stereoselectivity observed at the removed stereocenter [24][25]. Replacing N-benzylproline for 2,7-dihydro-1H-azepine (L5) allowed obtaining a new tridentate ligand with chemically stable axial

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

• a net iminyl-nitrooxylation reaction [140]. In 2020, Wei and co-workers studied an iminyl radical-triggered 1,5-hydrogen atom transfer (HAT) and [5 + 2] annulation processes for the synthesis of azepine derivatives 170 (Scheme 36) [141]. The reaction was tolerable of both electron-donating and

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• N-heterocyclic compounds such as phenanthridine, carbazole, and dibenzo[b,d]azepine. Simultaneously, Guo’s group published the arylation of nucleosides bearing a purine moiety. The transformation was regioselective and tolerated various substituents at the N9 position of the purine, including sugar

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• ), 3.48–3.42 (m, 1H), 2.65–2.59 (m, 1H), 2.06–2.00 (m, 2H), 1.86–1.78 (m, 2H), 1.53–1.27 (m, 7H); MS m/z (% relative intensity): 282 (100), 283 (18.4), 284 (1.6). 1,3,4,4a,5,11a-Hexahydro-6H-dibenzo[b,e]azepine-6,11(2H)-dione (8): 4 mg (4%), oily crystals; 1H NMR (CD3OD, 300 MHz) δ 7.83–7.77 (m, 1H), 7.71

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• hydrogens in the azepine ring: electrocyclization proceeds via a conrotatory mechanism due to the antisymmetry of the HOMO (Figure 2). The selective formation of a single diastereomer in the 1,3-dipolar cycloaddition reaction is likely a result from secondary interactions of orbitals of the π-systems of the

• -recovery technique with a π-pulse for inversion and a two-pulse ESE sequence for detection. The π-pulse lengths were nominally 20 ns. X-ray structure of compound 1 (one of the two enantiomers present in the crystal). A possible mechanism for the trans-position of the methyne hydrogens in the azepine ring

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• -2-naphthols [81]. These bifunctional compounds were reacted with various cyclic imines such as 4,5-dihydrobenzo[c]azepine or 6,7-dihydrothieno[3,2-c]pyridine to have new naphthoxazinobenzazepine 44 and -thienopyridine 45 derivatives [82]. Transformations at 80 °C in 1,4-dioxane as solvent were

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• cyclization products such as 2,1-benzisoxazole-3(1H)-one (2a) and 2-oxo-3-carboxy-3H-azepine (3a) has been reported [30]. The structure of benzisoxazole 2a was determined by IR, 1H and 13C NMR spectroscopy and by comparison of its mass spectrum with the corresponding spectrum from the NIST library (NIST

• ethanol. As can be seen in Table 3, the photolysis of 1c,d in a 1,4-dioxane/water mixture under these conditions lead to decreased yields of 2c,d and to the formation of azepine 3c and primary amines 4c,d with significant yields. An explanation for the decreased yields observed for isoxazoles 2c,d may be

• formation of azepines 3. This confirms the suggestions of previous reports [61][62] about the impossibility of ring expansion of such aryl azides. Interestingly, under these conditions (Table 3), the yields for 3H-azepine 3a and 3c were determined as 20 and 18%, respectively. We wondered if the yields of

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• (Scheme 49). Homologous starting material 242 underwent a RRM with catalyst 2 in the presence of ethylene (24) at 80 °C to produce indolizidine-based compound 243 in 63% yield. Under similar reaction conditions, the azabicyclic system 244 generated pyrrolo[1,2-a]azepine derivative 245. When the RRM

• protocol was applied to compounds 246a–c with different bridgehead substituents, they also generated the corresponding pyrrolo[1,2-a]azepine derivatives 247a–c in good yields with a high degree of regioselectivity (Scheme 50). Treatment of ether-bridged triene 248 with catalyst 2 in chloroform at 50 °C

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• occur (Scheme 6), no evidence for the expected azepine product 27 was seen. An attempt to separately dehydrate 26, by reaction with P2O5 resulted in an inseparable mixture. However, the same compound under basic conditions (Cs2CO3) in DMF at 85–87 °C (20 min) produced 17 in 89% yield, thereby providing

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• Tapan Saha Ratnava Maitra Shital K. Chattopadhyay Department of Chemistry, University of Kalyani, Kalyani - 741235, West Bengal, India 10.3762/bjoc.9.327 Abstract A common approach to the important protein kinase inhibitor (−)-balanol and an azepine-ring-modified balanol derivative has been

• natural product. Based on the information [48][49] that balanol binds to the ATP-docking site of protein kinase, all the three distinct domains present in the natural product such as the benzophenone core [50][51][52], the azepine core [53][54][55][56][57][58][59] and the p-hydroxybenzamide [60][61] unit

• oxidations involving the aldehyde 16 as the intermediate. Taken as a hole the described synthesis of 7 from 8 and 9 proceeded in eight linear steps in an overall yield of 22%. The synthesis of the azepine unit [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] was achieved following our

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• productivity of the Vycor reactor illustrates the importance of glassware choice for UV transmission. The N-pentenyl substituted dimethyl maleimide 78 underwent a [5 + 2] photocycloaddition to the corresponding azepine 79 with a productivity of 39 mmol/h. The same reactor was also used to optimise the [5 + 2

• ] cycloaddition of N-pentenyl-3,4-dichloromaleimide 80 (Scheme 26), a substrate sensitive to over-irradiation due to secondary reactions of the bicyclic azepine product 81. The scale-up of this reaction was hugely impractical as a batch process. For the maximum tolerated concentration of 0.02 M, the product can

• ]. The key step utilised the [5 + 2] cycloaddition (Scheme 27) for the construction of the pyrrolo[1,2-a]azepine core 83. As a batch process, this particularly sensitive reaction could only be performed on a 50 mg scale giving yields from 40–60% with full consumption of starting material. It would

Valence isomerization of cyclohepta-1,3,5-triene and its heteroelement analogues

• Helen Jansen,
• J. Chris Slootweg and
• Koop Lammertsma

Beilstein J. Org. Chem. 2011, 7, 1713–1721, doi:10.3762/bjoc.7.201

• necessitates a brief overview of the parent all-carbon system. This section is followed by one in which experimental data on the oxepine, thiepine, 1H-azepine, and 1H-phosphepine valence isomerizations are compared with those obtained by theoretical calculations. Computational methods have the advantage that

• ]. The calculated barrier of 8.3 kcal·mol−1 for thiepine (5) is nearly twice as large, possibly due to the higher antiaromatic destabilization of the flattened thiepine ring [40], but the interconversion of the boat forms of azepine and phosphepine are about equally favourable, requiring 3.0 [41] and 5.2

• thermally robust dibenzo[b,f]thiepines, which are of interest for their potent biological activity, illustrated by the psychosedative and antipsychotic properties of zotepine (18; Figure 2) [76][77][78][79][80]. 1H-Azepine – benzene imine The parent 1H-azepine (7) [81] was first generated in 1963 by Hafner

Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes

• Elena Borsini,
• Gianluigi Broggini,
• Andrea Fasana,
• Chiara Baldassarri,
• Angelo M. Manzo and
• Alcide D. Perboni

Beilstein J. Org. Chem. 2011, 7, 1468–1474, doi:10.3762/bjoc.7.170

• pyrrolo-azepine derivatives, as already described in the literature by Beller and coworkers [18]. In order to shed light on the structural features determining the size of the newly formed ring, we thought it appropriate to extend this study further to N-propargyl-1-methylpyrrole-2-carboxamides bearing a

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

• ]. Overall, aryl azides, which are simple to prepare from the corresponding aniline derivative, are convenient precursors for the synthesis of azepine derivatives. However, the utility of the process is offset by the long reaction times required and by the low yields arising from poor selectivity and

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• furanyl intermediate featuring an iminium ion (XI). This species undergoes an intramolecular cyclization to yield the observed azepine product, and regenerates the gold catalyst. Very recently, the same group reported a related gold-triggered formal (4 + 3) cycloaddition between nitrones and 1-(1-alkynyl

• propargylic benzoates with α,β-unsaturated imines to give azepine products 35 with excellent yields [77]. The formal (4 + 3) cycloaddition takes place in three basic stages: 1) Generation of the gold carbenoid by a 1,2-acyloxy migration, 2) attack of the imine on these electrophilic species to give an allyl

• with alkenes [70]. Gold-catalyzed intermolecular hetero-dehydro Diels–Alder cycloaddition [72]. Gold(I)-catalyzed stereoselective olefin cyclopropanation [74]. Reaction of propargylic benzoates with α,β-unsaturated imines to give azepine cycloadducts [77]. Gold-catalyzed (3 + 3) annulation of

Intramolecular hydroamination of alkynic sulfonamides catalyzed by a gold–triethynylphosphine complex: Construction of azepine frameworks by 7-exo-dig cyclization

• Hideto Ito,
• Tomoya Harada,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2011, 7, 951–959, doi:10.3762/bjoc.7.106

• investigated. The protocol, with a semihollow-shaped triethynylphosphine as a ligand for gold, allowed the synthesis of a variety of azepine derivatives, which are difficult to access by other methods. Both alkynic sulfoamides with a flexible linear chain and the benzene-fused substrates underwent 7-exo-dig

• cyclization to afford the nitrogen-containing heterocyclic seven-membered rings, such as tetrahydroazepine and dihydrobenzazepine, in good yields. Keywords: azepine; cyclization; gold catalyst; hydroamination; triethynylphosphine; Introduction Nitrogen-containing heterocyclic seven-membered rings are found

• heterocyclic seven-membered rings, and we applied the triethynylphosphine–gold(I) catalytic systems to the synthesis of azepine derivatives through intramolecular hydroamination of alkynic sulfonamides. This article describes the results of the optimization of reaction conditions, exploration of substrate

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

Synthesis of densely functionalized enantiopure indolizidines by ring- closing metathesis (RCM) of hydroxylamines from carbohydrate- derived nitrones

• Marco Bonanni,
• Marco Marradi,
• Francesca Cardona,
• Stefano Cicchi and
• Andrea Goti

Beilstein J. Org. Chem. 2007, 3, No. 44, doi:10.1186/1860-5397-3-44

• α,α'-disubstituted hydroxylamines 3. Synthesis of piperidines 15–16 and azepine 17. Reagents and conditions: a) Ac2O, THF, 1 h, rt for 8 and 9, reflux for 10; b) 2nd generation Grubbs' catalyst 11 (5 mol%), CH2Cl2, reflux, 5.5 h; c) KHCO3, MeOH, rt, 12 h; d) Zn, AcOH, rt, 2 h. Synthesis of