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

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

• electrophilic fluorine in the best case gave 15% conversion for NFSI and less than 8% isolated yield of 7c for SF. The major product in these reactions was 5, due to a β-elimination of the amine. In comparison, the reaction of 15 with NBS afforded 7b in an unoptimized yield of 48% after hydrolysis, which

• demonstrated that halogenation reactions with 15 were viable, but dependent on the characteristics of the electrophile. To avoid the elimination of the amine, β-methyl ether 16 was prepared. The reaction of ketone 16 with Selectfluor promoted by ʟ-proline in MeOH/MeCN, which ensured that the equilibrium

• species in situ was crucial for this transformation. By modifying a procedure for the trifluoromethylation of ketene dithioacetals reported by Liu and co-workers using TMSCF3 [43], rapid consumption of enamine 15 was observed. Acidic treatment of the intermediate promoted the hydrolysis/elimination

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• as reductive elimination [62]. G. Liu and Stahl disclosed an elegant methodology to functionalize benzylic C–H bonds via copper catalysis [30]. Under the catalytic conditions, alkylarenes were converted to benzylic nitriles in good yields and excellent enantioselectivities. In the proposed mechanism

• , a chiral Cu(III) complex forms from an achiral benzylic radical and a Cu(II)–CN species, and subsequent reductive elimination affords the enantioenriched benzylic nitrile product. Recently, X.-Y. Liu and co-workers reported an enantioselective aminofluoroalkylation of alkenes using a Cu(I)/chiral

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• (THF) was used as solvent, the proton elimination and protodeauration led to the formation of dihydrophenanthrene 12 due to solvent effects (Scheme 3, path b). This pathway-controlled approach for the syntheses of phenanthrenes complemented the established protocols. In 2020, Mutra et al. achieved a

• ]. Ph3PAuCl/AgOTf catalyzed a tandem 7-exo-dig cyclization followed by a cyclobutyl ring expansion process, yielding intermediate 84. The deprotonation followed by protonolysis-mediated gold elimination delivered the ring-expanded product 85 (Scheme 18, path a). When a bulkier ligand was used, steric

• (Scheme 28, path b). When IPrAuNTf2 was used as the catalyst, product 138 was obtained via a 6-exo-dig cyclization, whereas when Ph3PAuNTf2 was employed as the catalyst, product 139 was exclusively obtained through a hydroarylation/isomerization/elimination pathway. This work disclosed an unprecedented

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• formed to minimize steric clashes. Finally, reductive elimination leads to the formation of N,N-diarylhydrazine (D), which has been identified and characterized during the optimization process (see Supporting Information File 1 for details). In a second catalytic cycle, the N,N-diarylhydrazine (D

• carbonate, yielding the Pd(II) intermediate G. This intermediate then undergoes β–H elimination to afford the desired azobenzene product, along with a Pd(II) species H. Finally, reductive elimination regenerates Pd(0), completing the catalytic cycle. Then, a general reaction pathway for the formation of

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• Table 3. The preliminary ADME investigation, characterized by first-order kinetics due to low substrate concentration (≤10 µM), aids in establishing intrinsic clearance (Clint), which indicates the predicted elimination efficacy of drugs [43]. According to the generally accepted Clint ≈ 10 μL/min/kg (or

• -zero sample. The natural logarithm of the percentage remaining was plotted against incubation time to determine the first-order elimination rate constant (k) using linear regression. The half-life (t₁/₂) was calculated using Equation 4: Intrinsic clearance (Clint) was calculated and scaled to in vivo

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• reversible C–H activation to give the six-membered intermediate C. Substitution of the acetate ligand in C by 3 caused the generation of complex D. The six-membered ruthenacycle E was then obtained by migratory insertion of acetylene into the Ru–C bond. Finally, reductive elimination of E formed the target

• five-membered rhodacycle B, which underwent alkyne coordination followed by nucleophilic cyclization with 20a to give the biindolyl–Rh species D. The reductive elimination of D produced the bisindole-ligated CpxRhI intermediate E, which performed anodic oxidation to finish 21a and regenerate A. Notably

• of 22 with Cu(OPiv)2 and the following anodic copper(II) oxidation provided copper(III) carboxylate intermediate B. Facile carboxylate-promoted C–H activation and ligand exchange with 23 formed the copper(III) species D, which underwent metalation/reductive elimination to generate intermediate E

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165