(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• were rare, but a number of practical approaches have been disclosed in recent years. Many of these utilise the ability of bicyclo[1.1.0]butanes (BCBs) to undergo [2σ-2π]-type cycloadditions with alkene reaction partners [37]. Brown and co-workers used this approach to synthesise a variety of 1,2-BCHs

• catalytic system of B2cat2 and 4-phenylpyridine to form pyridine-boryl radicals which initiated ring expansion. The method was shown to be similarly tolerable of functional groups as Procter’s synthesis. Intramolecular crossed [2 + 2] cycloadditions offer an alternative approach to 1,2-disubstituted BCHs

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• purification by column chromatography prior to their on-surface deposition. By way of example, the synthesis of decacene precursor 59 was achieved in three synthetic steps by iterative [4 + 2] cycloadditions with an overall yield of 4.7% (Scheme 17). The synthesis of epoxyacene 59 started with the mono-Diels

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

• opening. Keywords: cycloadditions; DFT calculations; [70]fullerene; open-cage fullerenes; rhodium; Introduction The discovery of C60 (buckminsterfullerene) in 1985 [1] initiated the search for possible technological applications of fullerenes. Nowadays, applications for these carbon-based molecules have

• 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

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

• 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

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• the dimerization of two neutral C60 molecules were also computed for comparison (Table 1). As products, we have considered dimer 1-D2h and dimer 1-Cs, which are products of reversible [2 + 2] cycloadditions (phase 1) between two [6,6]-bonds in the former case and, between a [6,6]-bond and a [6,5]-bond

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

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

• cycloadditions from bay regions of [N]phenylenes, metal-catalyzed cycloadditions with diphenylacetylene occurred exclusively in the non-bay region, which allowed for straightforward syntheses of curved structures. Moreover, the presence of methyl groups in the structure facilitated the controlled activation of

• via [2 + 2] and [2 + 2 + 2] cycloadditions. In a closely related study conducted by Grill et al., the behavior of 2,3-dibromoanthracene (89) was examined on two distinct surfaces [Au(100) and Au(111)] (Scheme 19) [52]. Notably, on the Au(111) substrate, nearly equivalent quantities of dimer 91

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• organocatalysts is well-established in several organic reactions, including but not limited to aldol reactions [6], Michael additions [9], Mannich reactions [10], aza-Henry reactions [11], and Diels–Alder cycloadditions [12][13]. Although the benefits of organocatalysts are undoubted, their synthesis is often a

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

• regioselective [3 + 2] cycloadditions [59][60][61][62][63] (Scheme 10a). Similarly, trifluoroacetonitrile imine reacted with mercaptoacetaldehyde and mercaptocarboxylic acids to generate fluorinated 1,3,4-thiadiazines with good yields via a [3 + 3] annulation [64] (Scheme 10b). Meanwhile, mercaptoacetaldehyde as

• reported practical methods, which extended the structural scope of such dipoles. This has allowed the synthesis of trifluoromethylpyrazoles by a range of regioselective [3 + 2] cycloadditions of trifluoroacetonitrile imines with electron-poor olefins [73][74][75][76] (Scheme 11b). Moreover, the

• 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

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

• Pharmacy, Changzhou University, Changzhou 213164, China 10.3762/bjoc.19.123 Abstract The [3 + 2] cycloadditions of stabilized azomethine ylides (AMYs) derived from amino esters are well-established. However, the reactions of semi-stabilized AMYs generated from decarboxylative condensation of α-amino acids

• ][56][57][58]. The [3 + 2] cycloadditions of AMYs B1–B4 with alkenes lead to the formation of cycloaddition products 3a–d with attenuated regio- and stereoselectivity, since the Ar group is not strong enough to fully localize the negative charge on the carbon connecting to Ar in the 1,3-dipoles. Both

• 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

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

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

• the Nobel Prize in 2022 to M. Meldal, K. B. Sharpless and C. R. Bertozzi did not come as a surprise. In most cases the (3 + 2) cycloadditions were performed with isolated (and purified) organic azides, but it was early found that one-pot processes generating the potentially hazardous azides [22] in

• converted into several multivalent compounds B by amine or amide bond formations [44][45][46][47]. The transformation of the corresponding azidopyrans and azidooxepanes C or E into multivalent 1,2,3-triazole derivatives D and F by Meldal–Sharpless cycloadditions with suitable alkynes proceeded generally in

• . In this study we investigated the compatibility of the nucleophilic substitution of 1,2-, 1,3- or 1,4-bis(bromomethyl)benzene H with sodium azide and the copper-catalyzed alkyne–azide cycloadditions with compounds of type G to provide divalent compounds I (Scheme 1). These may serve as precursors of

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

• employed in numerous reactions such as metallocarbene chemistry [3][4][5][6][7][8], cycloadditions [9][10][11][12][13][14], and radiofluorinations [15][16][17][18]. As with most HVI reagents, reactions of iodonium ylides are often described using terminologies (e.g., ylide transfer, coupling or reductive

• reported by Hadjiarapoglou, Varvoglis and co-workers [107][108][109][110][111][112] and Moriarty et al. [113][114][115], who observed metal-free cycloadditions between iodonium ylides and olefins in the absence of a transition metal catalyst. These reactions proceeded under mild conditions without catalyst

• cyclopropane 22a. Interestingly, Hadjiarapoglou also revisited their investigation of iodonium ylide cycloadditions and their associated mechanisms [120], using diphenylketene as a new reaction partner with dimedone iodonium ylide 6 (analogous to earlier work reported by Koser in 1975 [9]). Investigations by

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

• ][59][60][61][62][63][64], herein, we wish to report the use of 5,6-unsubstituted 1,4-dihydropyridines as electron-deficient alkenes in the Huisgen 1,4-diploar cycloaddition and as electron-rich alkenes in formal [2 + 2] cycloadditions for the efficient synthesis of isoquinolino[1,2-f][1,6

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

• cycloadditions of N-alkylbenzothiazolium salts (Scheme 1, entry 6) [17][18][19][20][21][22], MCRs of 2-methylbenzothiazole, acetylenedicarboxylates and active methylene compounds (Scheme 1, entry 7) [23][24][25], MCRs of (1,3-benzothiazol-2-yl)acetonitrile, aldehydes and acylcyanides (Scheme 1, enry 8) [3][26

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• initiates with the in situ reduction of Ni(II) to Ni(0) followed by the side-on coordination of the alkene and alkyne substrates to the metal center with subsequent oxidative cyclometallation to form a nickel metallacycle, similar to several reported Ni-catalyzed [2 + 2] cycloadditions [29][30]. Rather than

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

• Bilbao, Spain Instituto de Síntesis Química y Catálisis Homogénea (SQCH), Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain 10.3762/bjoc.19.37 Abstract The contribution to the energy barrier of a series of tethers in transannular cycloadditions of cycloalkenes with hydrazones has been computationally

• by the tethers, the entropy effects caused by them has also been studied. The analysis of the evolution of the electron localization function along the reaction revealed the highly concerted character of the reaction. Keywords: DFT; distortion model; hydrazones; transannular cycloadditions

• materials and the conditions used [5]. Some common types of TCRs include Diels–Alder reactions [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], photocycloadditions [21][22][23][24][25][26][27][28], and other types of multistep cycloadditions [29]. Steric hindrance can have a significant effect on

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

• 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

• reported far less commonly than their use in (4 + 3) cycloadditions [94]. Simple hydrocarbon allyl cations can also undergo (3 + 2) cycloadditions through a purely stepwise cation olefin cyclization-type pathway, but these generally give complex mixtures and low yields and show unpredictable substrate

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

• one-pot reactions were also developed by Zhang using the 4-aminoquinoline synthesis, for example, in amino acids(esters)-based [3 + 2] cycloadditions [38][39][40][41][42][43][44][45][46][47][48] and in the synthesis of pyrrolidine-containing systems [49][50][51][52][53][54][55][56][57][58][59

• -component reaction for the synthesis of compound 5. Proposed mechanism for the double [3 + 2] cycloadditions. The synthesis of compound 5a with ᴅ- and ʟ-cysteine. Two-step (process A) vs cascade (process B) synthesis of 5a. i) 1.0:1.15 of 1a/2, EtOH (0.05 M), 25 °C, 6 h. ii) 1.1:1.0:1.0 of 1a/3a/4a, EtOH

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• Margetić used dibrominated polycyclic imides as substrates to generate reactive alkenes, which could be trapped in situ by several dienes through Diels−Alder cycloadditions by ball milling (Scheme 3) [7]. Further, Moores and co-workers synthesized phosphorus-bridged heptazine-based carbon nitrides (g-h-PCN

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• polymerizations [57][58][59], arylations and borylations [60], trifluoromethylations [61], as well as dehydrogenative couplings and cycloadditions [62], among others [63][64] in which mechanically polarized piezoelectric materials triggered redox chemistry. Alternative strategies to transduce mechanical force to

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• cation cycloadditions using (photo)electrochemical single-electron transfer in lithium perchlorate (LiClO4)/nitromethane (CH3NO2) solution [36][37][38][39][40][41][42][43][44]. During the course of our studies, we found that the TiO2 photoelectrochemical approach was more beneficial than simple

• trend is observed in photosensitized [2 + 2] cycloadditions [48]. Since their report was not a [4 + 2] but a [2 + 2] reaction and they proposed an energy transfer mechanism as opposed to an electron transfer pathway, it cannot be directly compared to our results. Even so, it would be fair to say that

• there is some correlation between these arylidene cycloalkane cycloadditions. Control studies are summarized in Table 1. LiClO4, TiO2, and light were crucial for the reaction (Table 1, entries 1–4) and the equivalents of the diene 2 was also key (entries 5 and 6 in Table 1). The reaction was sensitive

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• reactions and denitrogenative annulation according to Roy et al. [11]. Copper-catalyzed azide–alkyne cycloadditions are initiated via the (dual) complexation of the alkyne, whereas denitrogenative annulation on 1,2,3,4-tetrazoles is assumed to start via complexation of the open-form azide 18 (see Scheme 4

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

• reductive amination/cyclization of enantiopure cis-cyclopropane dicarbonyls [26]. The strategy based on azomethine ylide cycloadditions to cyclopropenes enables ready access to a wide range of spiro-fused 3-azabicyclo[3.1.0]hexanes (Scheme 1a). Inspired by our recent achievements, we have focused on

• cycloadditions to stable azomethine ylide PRP (Scheme 1c). Results and Discussion The study commenced with testing the feasibility of the cycloaddition reaction between protonated Ruhemann's purple (PRP, 1) [28][29] and cyclopropene dipolarophiles 2. 1,2,3-Triphenylcycloprop-1-ene (TPC, 2a) [30] was chosen as a

• (MeOH) in 75% yield. Eventually, the constitution of 3a was unambiguously corroborated by NMR spectra. Given the results of previous studies [22][23] concerning cycloadditions of ninhydrin-derived azomethine ylides to cyclopropenes, it was suggested that the stable azomethine ylide 1 appears to react