SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• elimination of the organometallic intermediate would lead to the desired product (Scheme 1B, reaction 1). Unfortunately, this approach will not be compatible in the case of azidation since the copper, azides and alkynes present in the mixture are expected to undergo alkyne–azide cycloaddition reactions [28

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

• thermal [2 + 2] cycloaddition. The [2 + 2] cycloaddition reactions of empty C60 have been known to proceed with unsaturated substrates having HOMO levels suitable for the thermal or photoinduced single-electron-transfer (SET) process (Scheme 1) [14][15][16][17][18][19][20][21][22][23]. Although the

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

• holds significant promise for applications in the fields of medicinal chemistry, materials science, and photovoltaics. In this study, we investigate the regioselectivity of the rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions between diynes and C70 as a novel procedure for generating C70 bis

• regioselective [2 + 2 + 2] cycloaddition reactions as a means to tailor the properties of fullerenes for specific applications. Types of [6,6]-bonds together with the [5,6]-bond of C60 with their C–C distances in pristine C60 and C70. 1H NMR (CS2/CDCl3, 400 MHz) spectrum of compound 2a as a mixture of two

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• . Zhang, Ma, and W. Zhang reflects the state of the art in the α-amino acid-based [3 + 2] cycloaddition reactions of N–H-type azomethine ylides in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse bioactive heterocyclic compounds and natural products [9]. Computational studies

• of transannular cycloadditions of cycloalkenone hydrazones catalyzed by BINOL-derived phosphoric acid are reported in the Full Research Paper by Vicario, Merino, and co-workers [10]. Their methodologies can now be used to predict the reactivity of different substrates in other cycloaddition reactions

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• -triazole-4-carbimidamides with alkyl, allyl, propargyl, benzyl, cycloalkyl, and indolyl substituents at the N1 position . Keywords: Cornforth rearrangement; cycloaddition reactions; 3,3-diaminoacrylonitriles; heterocyclic azides; 1,2,3-triazole; Introduction Heteroaryl amidines are widely used in the

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

• spirooxindoles [36][37][38][39][40][41][42][43]. In the presence of Lewis bases, isatin-derived MBH carbonates usually undergo [3 + 2] and [3 + 3] cycloaddition reactions with a broad range of active C–C and C–N double bonds and 1,3-dipolarpohiles to give various five- or six-membered cyclic spirooxindoles [44

• ] cycloaddition reactions of MBH carbonates derived from isatins. Synthesis of spiro[indoline-3,5'-[1,2]diazepines] 3a–m. Conditions: α-halogenated acylhydrazone (0.2 mmol), MBH nitrile of isatin (0.1 mmol), Et3N (0.2 mmol), DCM (4.0 mL), rt, 24 h; athe α-chloro-N-acylhydrazone was used, for other compounds α

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• arene–oxanorbornadiene annulation reactions [40]. This study involved converting PAHs obtained through annulation and aromatization steps into curved PAH structures using metal-catalyzed cycloaddition reactions pioneered by Vollhart [41] and Kotora [42]. Unlike previous studies that reported

• -catalyzed formal [2 + 2] cycloaddition reactions but also the emergence of tetracene trimer 86 and tetramer 88 stemming from [2 + 2 + 2] cycloaddition reactions (Scheme 18). It is proposed that an aryne intermediate is formed after thermal activation and that the observed end products are formed from arynes

• 21. Synthesis of symmetric POAs 25a and 25b. Synthesis of POA 29 via palladium-catalyzed annulation/aromatization reaction. Synthesis of bisphenylene-containing structures 34a–c. Synthesis of curved PAH 38 via Pd-catalyzed annulation and Ir-catalyzed cycloaddition reactions. Synthesis of [3

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

• presence of Brønsted acid. In their pioneering research, Tanaka et al. reported the [3 + 2] cycloaddition reactions of trifluoroacetaldehyde hydrazones and glyoxals to give 4-hydroxy-3-trifluoromethylpyrazoles. The resultant pyrazoles containing a free 4-hydroxy group were easily converted to a variety of

• group has attracted a significant level of attention, and many trifluoromethylated pyrazoles have been used in medicinal products or in pesticides [66]. The [3 + 2] cycloaddition reactions are considered among the most powerful tools for the synthesis of versatile fluoroalkylated pyrazoles. Enol ethers

• trifluoromethylated 1,2,4-triazoles were synthesized with excellent regioselectivities in [3 + 2] cycloaddition reactions of trifluoromethylated hydrazonoyl chlorides with imidates, amidine and 1H-benzo[d]imidazole-2-thiols, all of which were individually reported by Wang, Deng and Cai, respectively [77][78][79

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

• with arylaldehydes are much less explored. The [3 + 2] adducts of α-amino acids could be used for a second [3 + 2] cycloaddition as well as for other post-condensation modifications. This article highlights our recent work on the development of α-amino acid-based [3 + 2] cycloaddition reactions of N–H

• anionic charge on the α-carbon connecting to the EWG. They are popular AMYs for 1,3-diploar [3 + 2] cycloaddition reactions with alkenes to generate pyrrolidines 1a–d with high regio- and stereoselectivities. They have been reported in a huge number (1,000+) of publications [18][19][20][21][22][23][24][25

• trifluoromethylated pyrrolidines As mentioned above, the unexpected double cycloaddition and low stereoselectivity are the major challenges for [3 + 2] cycloaddition reactions of semi- and non-stabilized AMYs derived from the condensation of amino acids with aldehydes. However, the reactions of amino acids with

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

• are available [2][3], only a couple of cycloaddition reactions has been reported [4]. For example, [3 + 2] dipolar cycloadditions to form saturated difluoroisoxazolidines [5][6] and difluoropyrrolidines [7] and [4 + 2] cycloaddition reactions with gem-difluoro-1,3-dienes [8]. The overall landscape of

• -promoted [22] azide–alkyne cycloaddition reactions [17][23][24]; however, most of these strategies use high temperatures [21][25]. Herein, we report the discovery of a novel, one-step regioselective method under mild conditions to obtain 1,4,5-trisubstituted-1,2,3-triazoles from gem-difluoroalkenes

• elimination, resulting in an SNV-like transformation [26]. We previously reported that α-fluoronitroalkenes could be effectively used as surrogates of α-fluoroalkynes in cycloaddition reactions with organic azides to construct 4-fluoro-1,5-disubstituted 1,2,3-triazoles regioselectively [27]. This two-step

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

• catalyst when products were obtained with excellent enantioselectivity (92% ee) (Scheme 46). 2.3 [3 + 2] Cycloaddition reactions In a [3 + 2] cycloaddition reaction, a three atoms dipolar moiety (1,3-dipole) adds across two atoms of an alkene or alkyne (1,3-dipolarophile) (Scheme 47). It is also known as

• -donors on the catalytic activity of NHC–Cu(I) complexes for azide–alkyne [3 + 2] cycloaddition reactions [67]. They determined binding constants of four NHC–CuCl complexes with two N-donors, which revealed that addition of phenanthroline to the NHC–CuCl enhanced the catalytic activity manifold. In fact

• explored the application of a thiazolylidene-based Cu(I) complex as catalyst for [3 + 2] cycloaddition reactions. They prepared an ethylene-linked bisthiazol-2-ylidene dicopper(I) complex 136 which showed high catalytic activity (Scheme 53). The activity increased upon addition of acetic acid, particularly

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• cycloaddition reactions that occur without transition metal catalysts, the unexpected initiation of single electron transfer (SET) processes or photochemical transformations, and even proton transfers that appear to defy pKa limitations. The reaction pathways followed by iodonium ylides and Lewis basic reaction

• was presumed to play a central role in these metal-free processes. Various cycloaddition reactions of iodonium ylides that were typically associated with metallocarbene-mediated processes were also operative in the absence of catalysts. The mild reaction conditions precluded researchers from proposing

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

• act as activated alkene to take part in various cycloaddition reactions [35][36][37][38][39][40]. For example, Lavilla and co-workers developed a Sc(OTf)3-catalyzed three-component reaction of 5,6-unsubstituted 1,4-dihydropyridines, arylamines and ethyl glyoxylate for the preparation of various pyrido

• , 1040, 914, 854, 769, 704 cm−1; HRESIMS (m/z): [M + Na]+ calcd for C29H30NaN2O8, 557.1894; found, 557.1891. Single crystal structure of the compound 4k. Single crystal structure of compound 5a. Single crystal structure of compound 6f. Various cycloaddition reactions of 5,6-unsymmetric 1,4

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

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• target diazo reagent 5, which contains both a trifluoromethyl and a difluoromethylphosphonate moiety, was isolated as a stable, non-volatile liquid (Scheme 2). To highlight the synthetic utility of the novel carbene precursor 5, subsequent [2 + 1] cycloaddition reactions with selected terminal aromatic

• diastereoisomer adopts trans configuration (Figure 1). Furthermore, terminal aliphatic alkenes as well as N-Boc-allylamine were subjected to [2 + 1] cycloaddition reactions with the carbene precursor 5. The results are summarized in Scheme 4. As observed, the procedure was successful with a series of terminal

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

• ; Introduction Transannular cycloaddition reactions (TCRs) are useful for the synthesis of complex natural products and other biologically active compounds with high efficiency and stereoselectivity [1][2][3][4]. There are several different ways in which TCRs can occur, depending on the nature of the starting

• and co-workers demonstrated for transannular Diels–Alder cycloaddition reactions of symmetrically tethered large systems (10–18-membered rings) [29]. In this context, we have recently reported the transannular enantioselective (3 + 2) cycloaddition of cycloalkenone hydrazones under Brønsted acid

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

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

• cation in (3 + 2) cycloadditions: 5,6-dihydro-1,4-dithiin-2-methanol as a stabilized allyl cation Allyl cations are versatile electrophiles for the allylation of various nucleophiles, but can also act as C3-π-systems in a range of cycloaddition reactions (Scheme 13) [84][85][86][87][88]. When combined

• with dienes, a swift (4 + 3) cycloaddition can happen, which is isoelectronic to a Diels–Alder reaction, and amounts to a homo-Diels–Alder reaction (Scheme 13a) [89][90]. Cycloaddition reactions of ‘naked’ unsubstituted allyl cations are usually not synthetically useful, as they lead to a mixture of

• untapped potential in this area of research, and expect the utility of these building blocks to grow in the coming years. In particular, the recently established options to elaborate and functionalize 1,4-dithianes using mild transition-metal-catalyzed couplings, and their use in cycloaddition reactions

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• on the success of the catalytic aza-Nazarov reaction. Keywords: α-methylene-γ-lactam; aza-Nazarov reaction; β-silicon effect; heterocycles; intramolecular cyclization; Introduction The rapid construction of aliphatic heterocycles from acyclic building blocks via cyclization or cycloaddition

• reactions constitutes one of the main pillars of organic synthesis [1]. In this respect, the all-carbon Nazarov cyclization of divinyl ketones represents a direct method for the synthesis of five-membered carbocycles [2][3][4][5][6][7][8][9]. Variants of the Nazarov cyclization with substrates bearing one

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• , such as aldol reactions, Michael reactions, cycloaddition reactions, etc. Organophotoredox catalysis has emerged recently as another important catalysis type which has gained much attention and has been quite well-reviewed. At the same time, there are a significant number of other processes, especially

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

• the past years are discussed. This review contains cycloaddition reactions, nucleophilic halogenation reactions, metal-free coupling reactions, formation of N-heterocyclic carbenes, and multicomponent reactions, mainly three-component reactions. The mentioned methodologies have been performed by

• more research using imidazole N-oxides as precursors to make this research field flourishing in near future. Review Cycloaddition reactions In 2020, Anton V. Kutasevich et al. unfolded a very interesting deoxygenative reaction procedure where 2-unsubstituted imidazole N-oxides reacted with ethyl

• of ethyl 2-cyano-2-(1,3-dihydro-2H-imidazole-2-ylidene)acetate derivatives via [3 + 2] cycloaddition reactions. C–H/C–Li coupling reaction of 2H-imidazole 1-oxides with pentafluorophenyllithium. Transition-metal-free coupling reaction of 2H-imidazole 1-oxides with polyphenols. Reaction conditions: 1

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• compounds to molecules containing an enone fragment. Cycloaddition reactions involving diazo and enone moieties are usually carried out using transition-metal catalysis [18][19][20], with catalyst-free reactions being carried out only with the participation of reactive unsubstituted diazomethane [21][22][23

• formal [4 + 1] cycloaddition (Scheme 1). Results and Discussion FPDs are highly reactive compounds [25][26] containing an highly electrophilic enone fragment which facilitates the course of cycloaddition and nucleophilic addition reactions. In recent years, some types of cycloaddition reactions were

• investigated for FPDs: the [4 + 2] cycloaddition with alkenes resulting in pyran-annulated products [27][28][29][30][31][32][33][34] and the [3 + 2] cycloaddition with nitrones resulting in isoxazole-annulated products [35][36][37] (Scheme 2). However, formal [4 + 1] cycloaddition reactions for FPDs remain to

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• advantages over the related enol silyl ethers [24][25]: they are more stable towards acidic conditions, their electronic character contributes to high regioselectivity in cycloaddition reactions, and they can be converted to many other functions, including their hydrolysis to ketones [26]. In the other hand

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

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

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• ]+ calcd for C39H39NaN3O12, 764.2431; found, 764.2413. Single crystal structure of compound 3k. Single crystal structure of compound 4a. Single crystal structure of compound 4c. Single crystal structure of compound 5. Representative cycloaddition reactions of phenacylmalononitriles. Proposed reaction

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

• cycloadducts in moderate to good yields with high diastereofacial selectivity. Moreover, several unstable 1,2-disubstituted cyclopropenes were successfully trapped by the stable 1,3-dipole under mild conditions. The mechanism of the cycloaddition reactions of cyclopropenes with PRP has been thoroughly studied

• using density functional theory (DFT) methods at the M11/cc-pVDZ level of theory. The cycloaddition reactions have been found to be HOMOcyclopropene–LUMOylide controlled while the transition-state energies for the reaction of 3-methyl-3-phenylcyclopropene with PRP are fully consistent with the

• [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