Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• providing additional reaction pathways such as in bicyclobutanes (Figure 1) [7]. An umpolung approach was previously used in α-substitution of tropone [8]. Cycloheptatrienes are commonly expected to generate aromatic tropylium ions. Tropylium ions are so stable that they are formed not only through leaving

• -group elimination but through intermolecular hydride-transfer reactions as well. Therefore, the expected strategy to establish a chemical bond with a cycloheptatriene core is a reaction of a tropylium ion derivative with a nucleophile. Such reactions may involve either carbon [9][10][11] or heteroatom

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• nucleophilic chloromethylenetitanium species that transforms a ketone into the corresponding alkenyl chlorides (Scheme 63) [199]. 1.10 Allylic substitutions Allylic substitution of readily accessible alkenyl chlorides bearing a suitable leaving group at the allylic position enables efficient introduction of

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• leaving group X. The second step is substitutive nitration of the latter with nitronium salts (NO2BF4, (NO2)2SiF6) or N2O5). The main limitations of this approach are the use of hazardous and expensive nitrating reagents and its inapplicability for preparation of nitro-NNO-azoxy compounds containing

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• rearrangement is one of the important reactions induced by HTIB. Similar to other hypervalent iodine(III) compounds, HTIB is known to have higher electrophilicity towards olefinic bonds. HTIB dissociates, adds onto the olefinic bond and subsequently acts as a good leaving group resulting in generation of a

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• -methylene group and an ester reduction/Appel reaction sequence to convert the ester moiety to an iodide leaving group. The right-hand fragment (E/F-ring) was synthesized from tert-butylsiloxyfuran 39. Commencing via an asymmetric allylic alkylation and an aza-Michael reaction, butanolide 40 was obtained in

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• traces of the desired product. Methods for the installation of a CF3-group on enones are limited, although approaches have been applied to quinones, uracils, flavones or arylenones via radical pathways [39][40][41][42]. As per the fluorination reactions, we envisaged that a leaving group in the β

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• possibility to access the core of this ring system with the nitrone intermediate shown in Scheme 1A. As a model study, we describe here efforts towards an intermolecular variant with the oxindole shown in Scheme 1B; in this case a leaving group X will be displaced by the oxime to give an intermediate nitrone

• leaving group and activated, electron-poor dipolarophiles has been reported [31][32]. Treatment of aldehyde 4 with hydroxylamine in toluene at 60 °C for 1–3 h resulted in loss of the aldehyde as judged by 1H NMR spectroscopy of the crude mixture. When this was carried out in the presence of N

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• work, based on the large conformational freedom that is given by the long, flexible linkers [51]. To achieve a convergent synthesis, we first designed the hexaethylene glycol linker 96, which features a tosylate leaving group at one end and a phenylboronic ester at the other end (see Figure 5). This

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• exploiting the participation effect of the neighboring protecting group [43][44], employing anomeric lactols as acceptors is more complex as lactols with the desired configuration are frequently difficult to obtain (e.g., through anomerization). In addition to the nature of the leaving group and promoter

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• analogy with an aza-Michael reaction first with the addition of iminoiodinane accompanied with reorganization of double bonds including attack of the negatively charged sulfur atom on nitrogen with subsequent elimination of iodobenzene as good leaving group. The diversity of the structure of the target

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• discussed in more detail and illustrated by specific examples. 1.1 C–O bond-forming cyclisations 1.1.1 Intramolecular Williamson etherifications: Discovered by Alexander Williamson in 1850, this reaction is an SN2 substitution in which a leaving group, typically a halide or sulphonate ester, is displaced by

• methods for oxetane synthesis, mainly due to its practicality and versatility. 1.1.1.1 Substitution of a leaving group: In 2017, Moody et al. developed a new route towards spiro-oxetanes 8 utilising a combination of 1,4-C–H insertion and Williamson etherification (Scheme 3) [38]. The methodology commences

• oxidation of the metal centre turns the cobalt into an excellent leaving group, allowing for an intramolecular displacement reaction that affords the oxetane ring and regenerates the Co(II) catalyst. In 2023, Silvi et al. described a versatile and practical methodology that couples Williamson etherification

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• -position (tele-substituted; Figure 1), distant from the halogen leaving group at position 5 [10]. A plausible reaction mechanism was proposed by Korsik et al. [10]. The antimalarial activity of series 4 triazolopyrazine scaffolds is generally reduced by substitution of an amine functionality at the 8

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• precise C–C and C–N cross-coupling reactions only at the site of the iodine – donors were attached to TTM by radical-mediated nucleophilic aromatic substitution SRN1. The leaving group is the para-chlorine atom, of which a TTM molecule has three. It is therefore less than surprising that during this SRN1

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• reduced electrophilicity of the ester carbonyl. In 2021, Dong and Xie reported the development of an azido Matteson reaction, which achieves carbene insertion into an N–B bond of aminoboranes 84 or 86 (Scheme 22) [53]. In this methodology, by controlling the carbene leaving group (alkyl chlorides/alkyl

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• synthesis of alkyl iodides was investigated. A tosylate functionality was employed as a leaving group in the iodination reaction. Finally, the desired fluorinated tosylate 9 could be isolated on a gram-scale in a moderate yield of 27% (Scheme 3a). Subsequently, the iodination of the tosylate has been

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• eponymous Tsuji–Trost reaction, they faced a significant limitation: poor regioselectivity with non-symmetrical allylic substrates 2. This constraint led to the predominant development of Pd-catalyzed methods using symmetric 1,3-disubstituted allylic substrates 1 that contain a leaving group in the allylic

• dependent on both the leaving group of the allylic electrophile and the choice of the supporting ligand. When (+)-1,2-bis{(2S,5S)-2,5-diphenylphospholano}ethane {(S,S)-Ph-BPE} (L1) was employed as the supporting chiral ligand, initially allylic chloride was found to provide the desired product 32 with

• optimization revealed LiOt-Bu and diphenyl phosphate as the optimal metal alkoxide and leaving group, delivering the desired product 32 in high yield and high enantioselectivity at room temperature with only 2 mol % catalyst loading. The scope of this transformation proved to be remarkably broad. In addition

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• nucleophilic species present in the reaction medium, MMS can act as a methylene source. Under hydrolysis conditions, it can be a source of formaldehyde (Scheme 5a), but with other nucleophiles, after nucleophilic addition, the sulfide group can work as a leaving group, allowing for a sequential domino process

• presence of an excellent leaving group (methyl sulfide) which permits further transformations during the domino sequences. This dual effect of MMS makes DMSO an interesting C1 synthon that works not only as a source of a methylene unit (-CH2-) in terms of formaldehyde surrogate, but also as a promotor of

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• reacts with hydrazine hydrate and is heated to reflux, forming a pyrazolinone 2. This product is then chlorinated at the α-carbon, introducing a leaving group, to yield 3. The parent pyrazolinone 3 is subsequently treated with a base (either K2CO3 or N,N-diisopropylethylamine) to form the bimane 4. For

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• required thermal decomposition of the diazonium salt to effect the cyclization. In the quest for mild (room temperature) and scalable conditions toward cyclic diaryl λ3-bromanes 1 we realized that bromanyl units possess leaving group abilities comparable to the diazonium moiety [1][15]. Hence, the

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• glycosylation. Conventional glycosylation involves the ‘nucleophilic substitution’ of the leaving group at the sp3 anomeric centre of the donor moiety with a suitable carbohydrate or non-carbohydrate-based aglycon with the help of an electrophilic promoter to form the equatorial glycoside 7 or the axial

• as the participating group facilitating the formation of a 1,2-trans glycoside (Scheme 2). In general, the cleavage of the activated anomeric leaving group of the glycosyl donor 9 leads to the formation of an electron-deficient oxocarbenium ion 10. The participating vicinal acyl group interacts with

• -2 position to obtain 1,2-trans glycosides showing orthogonal deprotection according to the need of the compound. They introduced (2-benzyloxyphenyl)acetyl (BnPAc, 43) as a versatile leaving group showing orthogonality to both acetyl and benzyl protecting groups [127]. This group, when placed in the

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• –CH2–(CF2)n–COOCH3) with triflate as leaving group in terminal position are easily accessible and versatile building blocks for attaching long chain acids (pKa 0–1) to substrates in Williamson ether-type reactions. Keywords: acid-functionalized porphyrin; electron-rich porphyrin; nickel porphyrin

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• capability to function as radical initiators. The use of diaryliodonium salts as efficient electrophilic arylating reagents in a wide range of organic transformations is due to their unique features such as solid-state nature, excellent stability, and the presence of a robust leaving group [39][40][41][42

• of the SO2CF3 leaving group from the intermediate. For the late-stage substitution of coumarins, Han and colleagues developed a method, using hypervalent iodine reagents. At 50 °C in the presence of a base, coumarin-based aryliodonium salts are produced. These salts undergo an intramolecular aryl

• from 6 on reacting with arynophiles 14 (Scheme 5) [59]. The reaction is unique due to its ability to functionalize position 3, despite its greater steric hindrance compared to position 5. The process involves deprotonation at the 3-position of the aryl(Mes)iodonium salts, followed by exit of a leaving

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• both β-keto thioesters and β-keto amides [40][41]. Li and co-authors achieved the synthesis of β-keto thioesters by CF3SO3H-promoted hydrolysis of α-oxo ketene N,S-acetals with an amino leaving group (Scheme 1a, path 8) [40]. Subsequently, using NaOH-promoted hydrolysis of α-oxo ketene N,S-acetals, we

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• . The α,β-unsaturated carbonyl compounds 60 can undergo cyclization with tosylhydrazine in situ to form pyrazoles 61 under alkaline conditions, with the tosyl group acting as a leaving group. Upon deprotonation at position 1 by a base, followed by nucleophilic substitution of halides, N-functionalized

• toluene [173]. N-Vinylimidazole, an alkene with a leaving group, was used to synthesize the 3-substituted pyrazoles 169 because, unlike acetylene, it is not gaseous and, therefore, easier to handle. Instead of vinylimidazole, vinyl azides 170 can also be used as alkyne surrogates. After the 1,3-dipolar