Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• accelerated 1,3-dipolar and Diels–Alder reactions [12][13], it is noteworthy that the anticipated diverse properties resulting from the derivatization of Li+@C60 have not yet been fully realized. To further leverage the unique properties of the novel ion-endohedral fullerene, achieving diverse property tuning

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• medical applications) and improving their stability, among other desirable properties. The most common reactions used to functionalize fullerenes are Diels–Alder and 1,3-dipolar cycloadditions and Bingel–Hirsch cyclopropanations [19][20]. In most cases, functionalization occurs while preserving the carbon

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• other derivatives in good yields [37] (Scheme 1). Later, Wu et al. described a diastereoselective 1,3-dipolar cycloaddition of trifluoroacetaldehyde hydrazones with α,β-ethenyl ketones to obtain polysubstituted pyrazolidines and pyrazolines. These reactions were carried out under two different sets of

• under basic conditions, and expanded the synthetic method to N-substituted acylhydrazones [106][107] (Scheme 18). In the early development of 1,3-dipolar cycloadditions of azomethine imines, the acyclic azomethine imines were unstable and their in situ preparation required Brønsted acid or thermal

• trifluoromethyl acylhydrazones as 1,3-dipolar agents to react with β-nitrostyrenes [114], maleates [115], cyclopentadiene [116] and maleimides [117] for the synthesis of CF3-substituted pyrazolidine derivatives. These reactions were conducted under basic conditions and in the presence of Cu(OTf)2 (Scheme 19a). As

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• -type AMYs in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse heterocycles related to some bioactive compounds and natural products. Keywords: [3 + 2] cycloaddition; decarboxylation; 1,3-dipolar; double cycloaddition; one-pot synthesis; multicomponent reaction; semi

• -stabilized azomethine ylide; Introduction The 1,3-dipolar cycloaddition of azomethine ylides (AMYs) [1][2][3][4][5][6] is a powerful method for the synthesis of bioactive pyrrolidine-containing compounds and natural product analogs [7][8][9][10][11][12][13][14][15]. AMYs generated from the reaction of

• products 3c and 3d can be used for a second cycloaddition to form products 4a and 4b. The non-stabilized AMYs C1 and C2 have neither an EWG nor an Ar group to localize the negative charge. The 1,3-dipolar cycloadditions of C-type AMYs lead to the formation of [3 + 2] adducts 5 or 6 with low regio- and

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• oxide E [23], which can be converted to the desired isoxazole with 1a through a 1,3-dipolar cycloaddition. Conclusion In conclusion, we have developed an efficient and concise synthesis of isoxazole nitrogen heterocycles by direct C–H-bond activation of methyl heteroaromatics. The method avoids using

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• -difluoroalkenes that subsequently undergoes a cycloaddition reaction. Results and Discussion While investigating 1,3-dipolar cycloaddition reactions between organic azides and gem-difluoroalkenes to obtain the 4-fluoro-1,4-disubstituted 1,2,3-triazole regioisomers, we observed an interesting reactivity while

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• 1,3-dipolar cycloaddition and belongs to the general category of [π4s + π2s] cycloadditions. It is an important method to construct a five-membered heterocyclic ring [66]. As discussed earlier, the Cu atom in NHC–Cu(I) complexes has nucleophilic character, which allows binding to the positive end of

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• ]). Mechanistic aspects of the CuAAC have been studied in detail [16][17]. Whereas the traditional 1,3-dipolar cycloaddition (Huisgen reaction) [18][19][20] of azides and alkynes requires often – but not always – relatively harsh conditions and proceeds with moderate regioselectivity only [21], the copper

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• ; isoquinolino[1,2-f][1,6]naphthyridine; Introduction Among various well-known cycloaddition reactions such as the 1,3-dipolar cycloaddition reaction, Diels–Alder reaction, and the Povarov reaction, the cycloaddition reaction of Huisgen 1,4-dipoles with activated alkenes received increasing attention [1][2][3

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• -benzothiazol-2-yl(diazo)acetates (Scheme 1, entry 3) [12], dearomative [3 + 2] cycloaddition reactions of benzothiazoles with cyclopropanes (Scheme 1, entry 4) [13][14][15], multicomponent reactions (MCRs) of benzothiazoles, isocyanides and 2-methylidenemalonates (Scheme 1, entry 5) [16], 1,3-dipolar

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• common reaction conditions. The reaction has been defined by Houk and Rueping as a (3+ + 2) monopolar cycloaddition [33] pointing out the protonated state of the imino nitrogen of the hydrazone in contrast to the well-known 1,3-dipolar cycloaddition of azomethine imines in which the terminal nitrogen has

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• of the synthesis and properties of various porphyrin-triazole hybrids, this review will discuss some of the key reactions involved in the preparation of triazole-linked porphyrin conjugates. Keywords: azide–alkyne; click chemistry; CuAAC; 1,3-dipolar cycloaddition; porphyrin; 1,2,3-triazole

• connect a porphyrin with a chromophoric group. Among these, the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction [1][2] of azides with terminal alkynes is a popular and well established process to link a porphyrin with other moieties via 1,2,3-triazole group [3] (Figure 1). The term “click

• ] exploited the concept of “click chemistry” for the construction of β-substituted-triazoloporphyrins 3a–c in 65–95% yield by the reaction of β-azidotetraphenylporphyrins 1 with various arylalkynes 2a–c via copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction in DMF at 50 °C in the presence of CuSO4

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• group) are especially favored here [92][93], and these allyl cations can also be seen as 1,3-dipoles, cross-conjugated by a carbonyl (Scheme 13b). As can be expected from this 1,3-dipolar nature, such amphiphilic allyl cations can also be used in (3 + 2) cycloadditions, though this has so far been

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• introduced in this study. Subsequently one equivalent of aldehyde and olefinic oxindole in situ were followed by decarboxylative 1,3-dipolar cycloaddition for diastereoselective synthesis of spirooxindolepyrrolothiazoles with generating 5 new bonds, 5 stereocenters and two heterocycles (Scheme 1C and Scheme

•  2C). Results and Discussion The optimized reaction conditions of stepwise, one-pot and cascade (two-step with one operational step) processes for N,S-acetalation and decarboxylative 1,3-dipolar cycloaddition were developed by using two equivalents of 4-bromobenzaldehyde (1a), ʟ-cysteine (2) and

• . Subsequent decarboxylation of thiazolooxazol-1-one I affords non-stabilized azomethine ylide (AY) for 1,3-dipolar cycloaddition with olefinic oxindole 4a to give spirooxindolepyrrolothiazoles 5 and 7. The endo-TS is more favorable than exo-TS for the 1,3-dipolar cycloaddition to afford the major and minor

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• reaction of Meldrum’s acid (26) and aldehyde 27 resulting in the formation of the electron-deficient enone 30, which then participated in a Michael-type addition reaction with 1,3-dipolar 2-unsubstituted imidazole N-oxide 28 to provide the intermediate 31. In the last step, the final product 29 was

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• bendazac [10], the anti-inflammatory agent benzydamine [11], and the antiemetic agent granisetron [12] are commercially available examples. In view of the abovementioned interest, an increasing number of approaches for the synthesis of 1H-indazoles has been recently reported, including 1,3-dipolar

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

• –Prakash reagent (TMSCF3) in the presence of Cs2CO3 as base in MeCN at 0 °C gave product 7 with a trifluoromethyl group. Stefani et al. reported the 1,3-dipolar azide–alkyne cycloaddition (AAC) of organotellanyl alkynes with organic azides in the presence of a copper reagent to form 5-organotellanyl-1,2,3

• regioselective 1,3-dipolar azide–alkyne cycloaddition to form 5-selanyl-1,2,3-triazole. The investigation of the biological activity of the compounds obtained in this study and the application of this synthesis route using other heterocycles, instead of imidazopyridine, are currently underway in our laboratory

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• 1,3-dipolar cycloaddition (1,3-DC) reactions of cyclopropenes to the stable azomethine ylide – protonated form of Ruhemann's purple (PRP) has been developed. Both 3-substituted and 3,3-disubstituted cyclopropenes reacted with PRP, affording the corresponding bis-spirocyclic 3-azabicyclo[3.1.0]hexane

• [15]. In our recent studies, great attention was paid to developing methods for the synthesis of spiro[3-azabicyclo[3.1.0]hexanes] based on 1,3-dipolar cycloaddition reactions involving azomethine ylides and cyclopropene dipolarophiles, and also the in vitro activity of some synthesized compounds has

• been explored [19][20][21][22][23][24]. To generate azomethine ylides, we used a classical method based on the reaction of cyclic carbonyl compounds with α-amino acids. Μono-, bi-, and tetracyclic carbonyl compounds were utilized in these studies. 1,3-Dipolar cycloaddition of cyclopropenes to

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• , β-ketoesters or β-ketoamides are a commonly used 2-step route to 3,4,5-trisubstituted isoxazoles [24][25]. Xiao Zhou et al. recently reported a direct access to 3,4,5-trisubstituted isoxazoles via an enolate-mediated 1,3-dipolar cycloaddition of β-functionalized ketones with nitrile oxides using

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• broad range of substrates, solvents, and reaction conditions; all these parameters have to be carefully planned to avoid low yields or even no product formation, as previously described for compound 1 [20]. Amongst the vast number of reported procedures, the 1,3-dipolar cycloaddition was performed with

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• -oxazoles are: the 1,3-dipolar cycloaddition of alkenes and alkynes with nitrile oxides, and the reaction of a three-carbon atom component, such as a α,β-unsaturated ketone or a 1,3-diketone with hydroxylamine hydrochloride [33]. Recently, Rosa et al. reported a useful procedure for the synthesis of various

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

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• combination of acidic α-carbon atoms, isocyano groups, and sulfonyl moieties [18]. In general, TosMIC undergoes base-mediated 1,3-dipolar cycloadditions with activated alkenes to provide pyrroles as products [18] (Scheme 1A). Recently, alternative functionalizations using TosMIC as a tosyl source of

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• Discussion Synthesis of L1-M, L2-M, and L3-M According to our experience, concerning the most bioactive structural arrangement, the ligands L1, L2, and L3 were selected for this study (Scheme 1). Using the known methodology developed by our group, the starting compounds endo-prolinates 1, generated by 1,3

• -dipolar cycloaddition [16][21][22], were submitted to the reaction with benzoyl isothiocyanate in refluxing acetonitrile to obtain compounds L1, L2 and L3 in good yields [16][21]. Due to the very low biological activity of these ligands by themselves, the chelation with nickel(II) and palladium(II) was

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• ]. The main approach in the synthesis of the tetrazoles is 1,3-dipolar cycloaddition between azide and nitrile. These reactions often follow the principles of “click” chemistry [20]. Although the formation of tetrazole in the Schmidt reaction of ketones was noted in the original study by Schmidt himself

• hazardous [26][27]. Some recent studies employ this reagent in the Schmidt synthesis of tetrazoles from ketones that are smaller in size and simpler than the steroidal ketones in this work [28][29]. For the synthesis of steroidal tetrazoles, most often 1,3-dipolar cycloadditions are being used. In this way

• , derivatives of bile acid, androstene, and cholestane were prepared, with the tetrazole ring not being fused to the steroid core [30][31][32][33]. Some fused steroidal tetrazole derivatives were obtained by intramolecular 1,3-dipolar cycloaddition [34][35]. It should be noted that the Schmidt reaction