Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• in 71% yield. A detailed mechanism for this transformation is shown in Scheme 24 below [98]. Here, the Rh(II)-induced elimination of N2 generates carbene 218, which is attacked by the adjacent allyl ether moiety to form unstable zwitterion 219. Sigmatropic rearrangement and acidic workup yielded 213

• known procedure [79]. Acidic treatment in MeOH and subsequent addition of MeLi furnished full acetal 301 (Scheme 35). Treatment with Tf2NPh yielded an intermediate enol triflate, which underwent a β-hydride elimination towards allene 302 upon addition of Pd2(dba)3. Next, ring opening of the full acetal

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• promote Hofmann elimination. To enhance the leaving ability of the nitrogen atom we prepared ammonium salts 3 of the obtained pyrrolidines via treatment with alkyl halides. Since the preparation of quaternary ammonium salts of pyrrolidines is straightforward, we employed a one-pot method for its synthesis

• . Second is a step-wise route through retro-Claisen reaction, formation of the carbanion at the α-position to sulfonyl group, and Hofmann elimination of the quaternary nitrogen at the β-position. Both routes lead to the formation of terminal vinyl sulfone C, which reacts with the nucleophile present in the

• reaction media to form 4-Nu-3-(sulfonyl)butan-1-amines 4. An attempt to obtain 3,4-bis(phenylthio)butan-1-amine via reduction of the sulfonyl group [43][44] of the product 4r with LiAlH4 gave an unexpected reductive elimination of the thiophenol moiety furnishing N,N-dimethyl-3-(phenylsulfonyl)butan-1

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• state S, which is stabilized by two new hydrogen-bonding interactions. Finally, elimination of [MeNH3]MeSO4 delivers the butyl ester product. In 2025, Dou et al. developed a metal-free alcoholysis of amides mediated by HBF4, exhibiting a very broad substrate scope (Scheme 12) [60]. The esterification of

• hydrogen chloride acting as a Lewis acid, enabling nucleophilic attack by the amine to form a tetrahedral intermediate Z. Subsequent intramolecular hydrogen shift, followed by elimination of dimethylamine, affords the protonated transamidation product. In 2021, Lee et al. discovered that carbon dioxide

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• rise to the isomeric terpin-4-yl cation 6b. By way of cyclopropane formation, a different, so called, thujyl cation 6c is conceivable. Elimination then furnishes the ring-contracted 5/3-ring systems from the original cyclohexyl intermediate to give sabinene (7) and α-thujene (8). Another example of a 6

• is initiated via protonation of geranylgeranyl pyrophosphate (GGPP, 12) at the terminal olefin with CpPS (= Clitopilus passeckeranis pleuromutilin synthase), forming the decalin system 12a. A cascade of 1,2-shifts delivers the carbocation 12b which undergoes ring contraction and elimination to give

• astellifadiene synthase) [69]. Geranylfarnesyl pyrophosphate (18) is first cyclised through 1,11- and 10,14-connections to the tertiary carbocation 18a, and undergoes the previously described ring expansion, cyclopentane cyclisation (analogous to Scheme 3, see above) to 18b. Elimination affords the triene

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• process. Subsequent computational studies, however, refined this mechanistic understanding, revealing that reductive elimination proceeds through coupling of the C(3) terminus of the η1-allyl fragment with the para-carbon of the η3-benzyl ligand (Scheme 6A, right) [75]. Together, these insights

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• the other mechanism is based on an E2 reaction, which involves the elimination of phosphoric acid accompanied by alkene formation. The phosphoric acid ester of a secondary alcohol releases phosphoric acid and alkenes through thermal degradation, which has been previously observed using isosorbide

• phosphoric acid through a hydrolysis or E2 elimination reaction. The generated phosphoric acid forms a salt with triethylamine. Next, the phenoxy anion activated by the amine undergoes a nucleophilic attack on the phosphorus atom of the salt of phosphoric acid, resulting in the formation of MPP with the

• elimination of H2O. Then, two MPP molecules undergo a dehydration condensation reaction to form DPpyP [56]. Finally, the phenoxy anion undergoes a nucleophilic attack on the phosphorus atom of DPpyP, and DPP is formed through the elimination of MPP. In the absence of triethylamine, the esterification reaction

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• ethanol (Scheme 5, VII). However, under these conditions only decomposition of 4g was observed, and neither deacetylated nor hydroxylated products were isolated. Interestingly, chromatography of 4g on neutral alumina resulted in elimination of the sulfonylimine group to give compounds 5g. Therefore, the

• led to the intermediate A. Elimination of ethyl/methyl acetate from intermediate A afforded anion B. The latter reacted in ethanolic solution with molecular oxygen [52] with the formation of peroxide anion C. The protonation of anion C with proton sources (residual water or/and solvent or 3a can serve

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• resulting intermediate was trapped with a side chain enolate (derived from a methyl ketone), successfully constructing the pentacyclic aspidospermidine core. The next three steps comprised nitrogen methylation, ketone reduction, and hydroxyl elimination to afford 186. In the final two steps, an ethyl group

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• transmetallation with a NiII complex generated by oxidative addition of the thioester to Ni0. Finally, reductive elimination from NiII furnishes the ketone. Given the strong Zr–S bond (BDE = 137 kcal/mol) [12], zirconocene is thought to play a key role in facilitating the oxidative addition of Ni0 to the thioester

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

• -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

• 1875, Louis Henry extended this transformation to ketone 4 (Scheme 1B) [46]. Exposure to PCl5 gave a mixture of chlorinated intermediates described as 5 and 6, which, upon prolonged treatment with ethanolic KOH, underwent elimination to afford allene 7. Henry also observed that thermal treatment of the

• corresponding alkyne 50 by elimination with LDA were achieved in superb yields (Scheme 10). Gross and Gloede introduced catechol–PCl3 as an effective reagent for the conversion of ketones to the corresponding alkenyl chlorides [62] (Scheme 11A). Hudrlik later demonstrated that, in the case of 2

• under the reaction conditions (acetate II). Subsequent addition of HCl to intermediate II generates chloride III, which undergoes elimination to yield the desired product IV. Kodomari and co-workers serendipitously discovered a related reaction in which a large excess of acetyl chloride (8 equivalents

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• presence of the allyl or propenyl group at different positions does not appear to affect the yields (Scheme 6). Importantly, it was observed that reduction and β-elimination of the organozinc reagent prepared from 29 took place during the cross-coupling reaction, thereby affecting the yield (Scheme 7) [60

• in the presence of the Pd catalyst. It follows that elimination and reduction must occur after Pd insertion and formation of a pallado–zinc intermediate which undergoes β-elimination and proton transfer. Seminal studies by Jackson [61] have reported related results with iodozinc N-Boc-ʟ-alanine

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• thiocyanic acid at the triple bond – vinylthiocyanate A (Scheme 2). Isothiazolium thiocyanate 2 is formed by the attack of the imino nitrogen atom on the sulfur atom and the elimination of the CN anion in the Z-isomer of intermediate A. On the other hand, intramolecular addition of the hydroxy group to the

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

• starting material was again the (S)-Wieland–Miescher ketone (34). This was transformed to nitrile 46 via a seven-step sequence consisting of protecting group manipulations, a double bond isomerization to position C5–C6, as well as a 1,2-cyanide addition, and subsequent elimination (Scheme 10). The cyanide

• selectively, and, through acid-catalyzed cyclization, the spiro-E-ring was fused. Elimination of the alcohol moiety at C13 installed the double bond in the correct position at C12–C13. Final Fmoc-deprotection furnished cyclopamine (6). In summary, the Zhu/Gao group disclosed the total synthesis of cyclopamine

• rearranged scaffold 85 in three steps. Acetyl protection and elimination at C9–C11, followed by a Birch reduction, yielded a dienone structure. The latter was then hydrogenated, a methyl group was installed in α-position to the ketone, and an enone was formed to give 81 over 12 steps. Then, 2-ethyl-5

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• donor, through a late-stage glycosylation. The aglycon 2 can be derived from the Δ14 olefin intermediate 3 via Mukaiyama hydration and several functional group transformations. In turn, 3 would be generated from the key C14α-hydroxylated intermediate 4 via an elimination process. For the synthesis of 4

• transforming it into the pivotal C14 β-hydroxylated steroidal intermediate. As shown in Scheme 2, a BF3·Et2O-promoted elimination afforded the 14-olefinated intermediate 3 in a moderate yield. However, the following Mukaiyama hydration to introduce the C14 β-hydroxy group was unsuccessful. Owing to the

• reagent [20], the key intermediate 8 bearing a butenolide motif was obtained in 76% yield. Next, with the aid of the strong Lewis acid Bi(OTf)3, the regioselective elimination of 8 was achieved to produce the Δ14 olefin intermediate 9 in 86% yield. Afterwards, we evaluated the reactivity of 9 towards

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• aldehyde 1, activated by protonation of the oxygen atom through structure ii, forming the intermediate aldol iii. In the presence of EDDA, water elimination occurs in intermediate iv, yielding the Knoevenagel adducts 3 or 4. Synthesis of novel imidazo[1,2-a]pyridine–thiazolidinone hybrids To further

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• system involves the efficient nucleophilic addition of an imidazolyl anion B to radical cation species A, generated via single-electron oxidation of electron-donating arenes 31. The azolide anion B is released from acylimidazole 9 through an addition/elimination sequence in the presence of an NHC

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• encumbered tricyclic lactone 84 via an intramolecular [6 + 2] cycloaddition (Scheme 8). Attempts to achieve an asymmetric version of the cycloaddition were unsuccessful. Treatment of the lactone with MeMgBr, followed by mesylation and elimination of the resulting hemiacetal, afforded enol ether 85. Reaction

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• epoxidation of the tetrasubstituted alkene followed by Grieco elimination yielded diene 92. Subsequent oxidation of the hemiacetal, saponification of the lactone, intramolecular epoxide opening, and Hoveyda–Grubbs (II)-catalyzed RCM afforded tetracyclic compounds 94 and its transesterification product 93

• oxidation with freshly prepared trifluoroperacetic acid in n-pentane converted 111 to bis-epoxide 112 with excellent stereoselectivity and yield. Subjecting 112 to oxidation and organoselenium-mediated regioselective α,β-epoxy ketone opening, followed by intramolecular transesterification and elimination

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• followed by reaction with CH(OMe)3 afforded acetal 17, which was then subjected to a CH2Cl2 solution of TMSOTf and iPr2NEt. A mixture of enol methyl ethers 18 were thus produced by an elimination reaction. Eventually, a site-selective bromination of the double bond over the electron-rich benzene rings with

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• development of potent fungicides. Keywords: dipolar cycloaddition; elimination; fungicide; nucleoside; oxazoline; Introduction Modern agriculture relies on various effective fungicides to combat crop diseases for achieving significant gains [1]. However, the long-term and widespread use of chemicals and

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• phenyl-substituted benzoisoquinoline derivatives. Two plausible reaction mechanisms were proposed in the study: one involving oxidative addition of Int 4, a five-membered rhodium cyclic intermediate, followed by reductive elimination and the other proceeding via a bimolecular nucleophilic substitution

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• trimethylamine N-oxide and Dess–Martin periodinane, α-selenylation, and hydrogen peroxide-induced selenoxide elimination led to unsaturated ketone 183, from which artalbic acid (180) was obtained through a series of chemical transformations. The synthetic versatility of the photoinduced carboborative ring

• formation of ketone 191. This was observed when BF3·Et2O, InCl3, TfOH, or ZnBr2 were used as catalysts. Elimination of a proton from C15 led to formation of alcohol 192 with a second exocyclic double bond in reaction mediated by ZnBr2, Bi(OTf)3, p-TSA or TFA. A 1,2-rearrangement or migration of C2 results

• was the product of the double dehydration of carbocations B and C. The regioisomer of alcohol 192, a tertiary alcohol 196, was formed as a result of the elimination of a proton from the C15 atom. It is noteworthy that the reaction of 1,2-oxirane 190 with InCl3, ZnBr2, TfOH, or Bi(OTf)3 resulted in the

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• deprotection followed by C–H insertion. However, when attempting to remove the ketal protecting group, only decomposition of the starting material was observed. A plausible explanation for this outcome is that the β-lactone ring, located at the β-position of the methyl ketone, may undergo facile β-elimination

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• (50) and D (52), respectively. Alternatively, nucleophilic addition of MeOH to 54a and 56a, followed by ring-opening elimination, arrived at the corresponding γ-keto aldehyde intermediates 72/73. Subsequent intramolecular aldol cyclization of these intermediates furnished gracilisoids C/G (51/55) and

• – was prepared from (+)-pulegone (77) through a six-step manipulation involving epoxidation, epoxide opening with sodium thiophenolate and subsequent concomitant retro-aldol, sulfoxidation, a one pot α-alkylation with acrylonitrile proceeding to thermal syn-elimination of phenylsulfenic acid, ketone

• EG3 (99) via TMSOTf/Et3N-mediated β-elimination of methanol followed by desilylation. Finally, stereoselective epoxidation and reductive opening of the oxirane ring enabled the total synthesis of preussomerin EG2 (98) from preussomerin EG1 (97) in 88% yield over two steps. In this synthesis, the