A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• Abstract This work presents an examination of the selective functionalization of norbornadiene through nitrile oxide 1,3-dipolar cycloaddition/ring-opening metathesis (ROM)/cross-metathesis (CM) protocols. Functionalization of commercially available norbornadiene provided novel bicyclic scaffolds with

• oxide 1,3-dipolar cycloaddition/ROM/CM strategies was presented. The stepwise functionalization of norbornadiene across the ring olefin bonds generated fluorine-containing alkenylated cyclopentane-fused isoxazolines. The synthetic protocol was based on selective nitrile oxide cycloaddition to the

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• applications of these five-membered N-heterocycles are the result of both their easy synthetic procedures and ring functionalization [9][31][32]. Typically, 1,2,3-triazole derivatives are prepared via a 1,3-dipolar cycloaddition reaction between azides and alkynes [33]. It is worth noting that the metal

• 1,2,3-triazoles through multicomponent reactions and the relevant mechanistic aspects have been surveyed by Chen, Ren, et al. [27]. The 1,3-dipolar cycloaddition reaction between azides and alkynes is the most efficient pathway for the preparation of disubstituted 1,2,3-triazole derivatives. The copper

• of the imine intermediate produces the intermediate enamine 13. The 1,3-dipolar cycloaddition of enamine 13 with azide produces intermediate 1,2,3-triazoline 14. In continuation, a ring-opening process is promoted by acetic acid to afford the intermediate 16. Afterward, triazene intermediate 17 was

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• stereoselective synthesis is especially interesting, highlighting the 1,3-dipolar cycloaddition reactions with azomethine ylides as an example of transformation that take place with great stereocontrol, and allow the synthesis of polyfunctionalized pyrrolidines in a single reaction step [91][92]. On the other

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• plausible mechanism shown in Scheme 14 explains the formation of azomethine ylide B by condensation of isatin with amino acid followed by release of a molecule of CO2 via A. The imine B undergoes 1,3-dipolar cycloaddition with the dipolarophiles 39. The cyclization yields the desired product 40 of the three

• introduces primary amines for 1,3-dipolar cycloaddition which is less explored due to the probability of competitive Strecker degradation over decarboxylation of azomethine ylides. The protocol reveals the efficiency of MW assisted reaction with reduced reaction time from 18 h to 12 min and enhanced the

• ylide formation over the expected Strecker degradation. The azomethine ylide trapped by 3-alkenylindole undergoes 1,3-dipolar cycloaddition and led to the cycloadducts 44. 4 Pyrans Pyran is a six-membered heterocyclic, non-aromatic ring, consisting of five carbon atoms and one oxygen atom with two

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• precursors in denitrogenative transannulation reactions under metal-catalysed conditions to form other heterocycles such as functionalized pyrroles, imidazoles and pyridines (Scheme 1b) [11][12][13]. The traditional method for the synthesis of triazole unit is the Huisgen 1,3-dipolar cycloaddition between

• -triazoles with alkynes and Rh catalysed N1 and N2 selective alkylations [24][25]. As for metal-free approaches, besides synthesizing N-alkylated triazoles via 1,3-dipolar cycloaddition of alkyl azide with enols generated from carbonyl compounds under transition metal-free conditions [26], a direct

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• C60 or b) possible formation of both isomers as a result of 1,3-dipolar cycloaddition of the diazo compound to the fullerene, followed by elimination of molecular nitrogen from the pyrazoline intermediate. Second, the rearrangement of [5,6]-open isomers into thermodynamically more stable [6,6]-closed

• unusual ferrocene-containing block 202 was synthesized (Scheme 37) [158]. 1-(3-(Benzoyl)propyl)-1-phenyl[6,6]methanofullerene (203) was obtained by 1,3-dipolar cycloaddition of a tosylhydrazone derivative (obtained from 1,3-dibenzoylpropane) to C60 (Scheme 38) [159]. 2-Benzoylpropionic acid was used as

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• chlorine at the purine C2 position by azide, and 3) copper-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) with different alkynes. Pathway B included: 1) the two-step synthesis of 2,6-bistriazolylpurine derivatives 6 from 2,6-dichloropurine derivative 1 [22] and 2) the SNAr–Arbuzov reaction with

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• forms. Key (homotropane construction) steps included: i) inter and intramolecular Mannich reaction; ii) double Michael addition in the cyclooctadienone derivative; and iii) intramolecular 1,3-dipolar cycloaddition. As shown in Scheme 1, the azabicyclononane ring is an interesting target for strategies

• nitrone. Murahashi synthesis – 2000 Starting from secondary amines, Murahashi et al. developed a method for preparing homochiral β-sulfinyl nitrones [41]. Accordingly, (+)-euphococcinine (2) was prepared through allylation followed by the 1,3-dipolar cycloaddition of β-sulfinyl nitrone 20 derived from

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• synthesis of complex natural products (Figure 2). The 1,3-dipolar cycloaddition has been well-documented and widely used for the construction of five-membered heterocycles since the 1960s [13]. However, the development of the all-carbon [3 + 2] cycloaddition, for instance, Berson’s and Little’s [3 + 2

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• chemistry and has attracted much interest. For 1,3-dipolar cycloaddition reactions microwave irradiation not only allows to reduce the reaction time and to increase yields, but in some cases also can affect the selectivity of the reaction [34][35][36]. The efficiency of microwave irradiation has been shown

• investigated using only convection heating. The aim of the current work is to investigate the regio- and diastereoselectivity of the microwave-assisted (3 + 2) cycloaddition of 6-aryldiazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones. Results and Discussion Herein, we report the 1,3-dipolar

• cycloaddition reaction of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes 1a–d (DABCH) with 1,3-diarylpropenones 2a–l at 110 °С under microwave irradiation using a microwave oven Discover SP in a 10 mL glass reactor. It was found that under these conditions the (3 + 2) cycloaddition products – perhydropyrazolopyrazoles

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• initiates the allylic rearrangement and thereby facilitates the removal of the crucial phosphonium oxide. The outcome of this process is the structurally relevant azido moiety IIIa, which then undergoes a 1,3-dipolar cycloaddition with the copper acetylide IVa to furnish the 1,4-disubstituted 1,2,3

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• -methanides (thiocarbonyl ylides) with electron-deficient ethylenic dipolarophiles. This method was extensively developed by Huisgen and co-workers in the 1980s [3][4][5]. In the course of these studies, a non-orthodox stepwise mechanism of the 1,3-dipolar cycloaddition was established by experiments

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• pyrrolidines II-b was less explored [27][28][29]. In recent years, our lab has reported a series of 1,3-dipolar cycloaddition-initiated methods for the synthesis of diverse heterocycles A–J bearing fused polycyclic rings such as tetrahydroepiminobenzo[b]azocines, tetrahydropyrrolobenzodiazepinones

• via sequential 1,3-dipolar cycloaddition, N-allylation, and intramolecular Heck cyclization reactions [50][51][52][53][54] (Scheme 2, K). Both stabilized and non-stabilized azomethine ylides could be used for the initial [3 + 2] cycloaddition. A multicomponent reaction was combined with one-pot

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• . Securinega alkaloids The total synthesis of the Securinega alkaloids, (−)-flueggine A (18) and (+)-virosaine B (19), which are potent anticancer agents, was proposed by Wei et al. [90] via a relay ring-closing metathesis (RRCM) associated with a 1,3-dipolar cycloaddition. The enyne precursors bearing a

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• reactions that are stereospecific, high-yielding, modular, wide in scope, executable under simple reaction conditions, conductable in safe or easily removable solvents, and that generate only nonoffensive byproducts. Of course, the classical Huisgen 1,3-dipolar cycloaddition does not fit into the above

• ]. Generally, urea (72) was calcined and then, CuCl2 was immobilized using sonication (Scheme 13). The nanopolymeric catalyst was applied as a reusable nanocatalyst for promoting the 1,3-dipolar cycloaddition of nitroolefins/phenylacetylenes and sodium azide in water at ambient temperature. High yields of the

• 4-aryl-1,2,3-triazole 76 were obtained in short reaction times. The results indicated that ß-nitrostyrenes/phenylacetylenes containing electron-rich and -deficient groups could participate in the 1,3-dipolar cycloaddition reaction. Notably, the reaction was also extended to bistriazole derivatives

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• , 8, 9, 12 and 13 were then prepared by [3 + 2]-1,3-dipolar cycloaddition of nitrile oxide (ArCNO) formed in situ from oximes and a number of alkenes as dipolarophiles, to yield the precursors of the cycloadducts isoxazolines 2, 7 and 11 regioselectively. The cycloadducts were subjected to SnCl2

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

• observed in a one-pot synthesis from cyclopentanone, dimethyl fumarate and ammonium acetate. This multistep reaction includes 1,3-dipolar cycloaddition of dimethyl fumarate to the cyclic azomethine ylide formed in situ from cyclopentanone and ammonia. The polycyclic amine product was easily converted into

• nitroxide [4]. Here we report the unexpected formation of a highly strained polycyclic amine from cyclopentanone, dimethyl fumarate and ammonium acetate. This multistep reaction obviously includes the 1,3-dipolar cycloaddition of dimethyl fumarate with cyclic azomethine ylide formed in situ from

• heterocycle formation [11]. Presumably, a prototropic shift in the enamine-imine intermediate 4 is followed by electrocyclization to the cyclic azomethine ylide, which then reacts with dimethyl fumarate in a 1,3-dipolar cycloaddition. The suggested mechanism accounts for the trans-position of the methyne

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• tethered to cyclohexadienones that can be converted into complex polycycles by Ag-carbenoid-initiated cascades [16]. Recently, Zhu’s group developed a tandem 1,3‑dipolar cycloaddition/cyclopropanation silver-catalyzed reaction of enynals with alkenes [17]. In our previous studies, this silver carbene

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• prospect of the tetrazole hybridization strategy in drug discovery. Among the most versatile methods for obtaining tetrazoles are the Ugi-azide four-component reaction (Ugi-azide-4CR) [14][15][16] and the 1,3-dipolar cycloaddition of azides with (acyl)cyanides [17][18]. The Ugi-azide-4CR enables the

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• synthesis of new pyrrolidine nitroxides from 5,5-dialkyl-1-pyrroline N-oxides via the introduction of a pent-4-enyl group to the nitrone carbon followed by an intramolecular 1,3-dipolar cycloaddition reaction and isoxazolidine ring opening. The kinetics of reduction of the new nitroxides with ascorbate were

• studied and compared to those of previously published (1S,2R,3′S,4′S,5′S,2″R)-dispiro[(2-hydroxymethyl)cyclopentan-1,2′-(3′,4′-di-tert-butoxy)pyrrolidine-5′,1″-(2″-hydroxymethyl)cyclopentane]-1′-oxyl (1). Keywords: aldonitrone; 1,3-dipolar cycloaddition; pyrrolidine nitroxides; 1-pyrroline-N-oxide

• -enylmagnesium bromide to the corresponding nitrone, oxidation to alkenylnitrone, intramolecular 1,3-dipolar cycloaddition, and isoxazolidine ring opening. Nitroxide 1 showed both an unexpectedly low reduction rate [6] and long relaxation times t1 and tm at room temperature [4]. Unexpectedly high resistance of

Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• Ullmann-type coupling to give aryl azide 2, which readily reacted with phenylacetylene in a copper-catalyzed Huisgen 1,3-dipolar cycloaddition to give 1,2,3-triazole 3 (Scheme 1). The formation of the ruthenacycle was then achieved using Albrecht’s method involving regioselective methylation of triazole 3

• our case column chromatography was only used once (to purify the monoazidocalix[4]arene 7), whilst the other procedure needed chromatography at each step. Introduction of the triazole moiety onto the upper rim of the calix[4]arene was then achieved with a copper-catalyzed Huisgen 1,3-dipolar

• cycloaddition between monoazidocalix[4]arene 7 and phenylacetylene, affording monotriazolocalix[4]arene 11 in 87% yield (Scheme 4). Methylation of the triazole was also achieved using excess iodomethane in a rather protracted reaction, to yield the calix[4]arene triazolium iodide salt 12 in effectively

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• our continuous efforts in asymmetric syntheses and applications of chiral 2-isoxazolines [49][50][51]. Results and Discussion Our synthesis commenced with a chiral 3,5-disubstituted-2-isoxazoline 3 or 4, which were prepared from silyl nitronate through an asymmetric 1,3-dipolar cycloaddition developed

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• four stereoisomers with low (ca. 3:1) diastereoselectivity and in a non-enantioselective manner (Scheme 46) [21]. Undoubtedly, it was the 1,3-dipolar cycloaddition of the azomethine ylide 180 with an electron-rich alkene. Fortunately, cycloadducts (2R,3R,4S)-, (2S,3S,4R)-, (2R,3S,4R)- and (2S,3R,4S