Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• 1b was provided by derivatization of both molecules in ways that confirmed their relative stereochemistry by taking advantage of the different symmetry elements present in each case. Thus, both reductive amination and hydride reduction of C2-symmetric 1a led to the isolation of the only possible

• (chiral) diastereomer of the products 3 and 4 in each case – reaction of the nucleophile with either face of the iminium ion or ketone gives the same diastereomer, as illustrated. By contrast, hydride reduction of 1b gave an approx. 9:1 mixture of products 5 and 6, as judged by the crude 1H NMR spectrum

• . The major product was isolated and assigned as 5 (from axial attack of a small hydride reagent) [24]. From analysis of the NMR spectra of 5, it was clear that the molecule retained symmetry following reduction, reflected in the reduced number of signals in both 1H and 13C spectra compared to alcohol 4

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• )pinoresinol had slight cytotoxicity at 10 µM. A transwell anti-invasive assay on the same compound showed a reduction in the invasion of adult U251MG cells by 50% and pediatric KNS42 cells by 30%, with IC50 values of 0.26 and 0.40 µM, respectively. Keywords: anti-invasive; cytotoxicity; Eremophila maculata

• ranging from 1.56−25 µM with a reduction of up to 65% invasion in comparison to the control [22]. Owing to the interesting biological activity of 2 and its moderate abundance in the seeds of E. maculata, we decided to generate five semisynthetic analogues 3−7 (Figure 2) and evaluate these compounds for in

• evaluations of (+)-pinoresinol (2) and its analogues 3–7 against the U251MG cell line, compound (+)-4,4'-di(3,3-dimethylbutanoyl)pinoresinol (6) showed slight cytotoxicity (19% cell viability reduction) at a concentration of 10 µM. Also, on the KNS42 cell line, only (+)-4,4'-di(3,3-dimethylbutanoyl

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• diastereomers (dr = 5:3) under Luche reduction conditions. These two diastereomers were difficult to be separated from each other using normal column chromatography and therefore were used in the next deoxygenation steps as a mixture. Attempts to form the xanthate for Barton–McCombie deoxygenation [61][62], or

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• reaction displays pronounced sensitivity to substituent patterns rather than electronic effects. Mechanistic investigations, including radical trapping, Stern–Volmer analysis, and DFT calculations, support a reductive quenching pathway involving photocatalyst-mediated reduction of TFAA. The protocol is

• conditions. Since the photocatalyst can function as both an oxidizing and a reducing agent, we examined the literature data to evaluate the possible reaction pathway. Based on the experimentally determined oxidation and reduction potentials of the excited state of 3DPAFIPN (E1/2(PC·+/PC*) = −1.38 V, E1/2 (PC

• */PC·−) = 1.09 V) [33], together with the reduction potential of TFAA (Ered = −1.2 V) [34] and the oxidation potential of TMB (Ered = 1.43 V) [35], it can be concluded that in our reaction the photocatalyst acts primarily as an electron donor. Accordingly, for the pair of TFAA and TMB, reduction of

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• reduction of over 80% in FGFR2 protein levels, with negligible effects on the other subtypes. These findings establish LC-JD-6 as a highly selective FGFR2 degrader. LC-JD-6 reduced the expression of membrane-bound FGFR2 Since most PROTACs reported to date act on intracellular targets, we examined whether LC

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• , National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan 10.3762/bjoc.22.43 Abstract The reduction of carbonyl compounds

• : bimetallic nanostructure; carbonyl reduction; continuous-flow reaction; heterogeneous catalyst; subatmospheric hydrogen; Introduction The reduction of carbonyl compounds, ketones and aldehydes to alcohols is a fundamental and important reaction in organic synthesis that can provide valuable chemicals such

• atmospheric pressure hydrogen conditions. In this article, we report the development of a continuous-flow carbonyl reduction system that achieves high performance and a wide substrate scope under atmospheric or subatmospheric hydrogen pressure and ambient temperature using Pt–Fe bimetallic heterogeneous

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

• used as a starting material and was protected as acetonide within the first step to enable the reduction of both acid moieties towards 14 (Scheme 2). Bn-protection, followed by oxidation and olefination yielded sulfone 15, which was vinylated leading to 16 as a single diastereomer. Further Grubbs

• metathesis with ethyl acrylate, acidic cleavage of the diol protecting group and addition of NaH induced the oxy-Michael reaction towards 18 in 4:1 dr. Reduction of the ester moiety, subsequent protection with TBDPSCl and methylation of the secondary alcohol furnished 19. After Bn-deprotection, iodination

• cuprate and acidic treatment afforded 25 in 13:1 dr. After protection with 2,6-DCBCl, reduction with LiAlH4, TBDPS-protection and methylation, 26 was received in 35% yield. Eventually, the addition of I2 triggered an iodocyclization towards 27. While in the first sequence only mg amounts of 22 were

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• were ipso-nitrated followed by reduction of the nitro groups. To prepare 2-azidoethylated macrocycles, the ipso-nitration/reduction sequence was applied to p-tert-butylcalix[4]arenes containing 2-tosyloxyethyl groups at the narrow rims followed by replacement of the tosyloxy groups with azide ones. In

• important functionalities which can be introduced into calix[4]arene structures either through a wide-rim exhaustive nitration followed by reduction of the nitro groups [5][6][7][8][9][10][11][12][13], or through azo coupling followed by cleavage of the calixarene azo compounds thus formed [14][15][16][17

• into various multifunctional structures and sophisticated supramolecular systems. Results and Discussion In the majority of cases, the introduction of four amino groups into the calix[4]arene wide rim requires exhaustive (ipso-)nitration of the core followed by reduction of the resulting p-nitrocalix[4

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

• of the quaternary ammonium salt in the presence of a O-, S- or N-nucleophile with cesium carbonate leads to a retro-Claisen reaction, ring-opening and Michael addition. The resulting novel 4-Nu-3-sulfonylbutan-1-amines are isolated in moderate to excellent overall yields. The reduction of the

• the fast increase of the molecular complexity, remains significant. Unlike the classical aminoethylation of nucleophilic compounds [28][29], Batey et al. recently developed a two-step approach consisted in addition of terminal ynimides I to various electrophiles with subsequent reduction of the C≡C

• 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

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• -alkynyl-substituted pyrrolidine nitroxides was studied. These nitroxides have been prepared via intramolecular Huisgen cycloaddition or intramolecular alkylation in 2-pyrazolyl derivatives prepared by Michael addition–cyclocondensation of the corresponding alkynones with hydrazine. The reduction kinetics

• by ascorbate showed that the formation of the rigid tricyclic framework does not lead to a significant increase in stability of the radical center to chemical reduction. Keywords: annulated tricyclic system; nitroxide; pyrazole; pyrrolidine; triazole; Introduction Stable nitroxides are functional

• acetoxy groups and reduction of the nitroxyl fragment to the corresponding hydroxylamine. Primary products were stirred with a solution of NaOH in methanol under aerobic conditions to achieve complete hydrolysis and regeneration of the nitroxide group. Pyrazole 9a was isolated with an overall yield of 33

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

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

• -arene complexes illustrates this perfectly (Figure 8B): Os(II) coordination partially localizes the π-system of the arene while protecting the coordinated double bond, enabling selective hydrogenation of the diene portion even under ambient conditions [53][54]. Reduction in the presence of a simple Pd/C

• Mo(I) species, followed by reduction in trifluorotoluene, afforded the enantioenriched trifluorotoluene complex with essentially complete retention at the metal stereocenter (er = 99:1). However, control of the metal stereocenter alone is insufficient: a defined interaction with the prochiral

• canonical illustration is provided by the two-electron reduction of the symmetric sandwich complex [Ru(η6-C6Me6)2]2+, which furnishes the neutral [Ru(η6-C6Me6)(η4-C6Me6)] species upon haptotropic rearrangement, in accordance with the 18-electron rule (Figure 11A) [96][97]. Through partial coordination, the

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• difluoromethyl moiety is significantly less repulsive in structure 4. In addition, the zigzag conformation of the N-alkyl chain reduces σCN/σCC repulsions. Structure 5 (type II) displays a comparatively low steric penalty (294.0 kcal mol−1), much smaller than those of structures 1–3. This reduction arises in

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• polymer hosts. In contrast, TADF relies on the reduction of the singlet–triplet energy gap (ΔEST), facilitating thermally activated reverse intersystem crossing (RISC) from the triplet state to the singlet excited state, where the excitation energy is released via delayed fluorescence [29]. Common

• triplet state. To further investigate the emission dynamics, temperature-dependent lifetime measurements were conducted, which revealed a clear and significant reduction in the emission lifetime as the temperature increased (Figure 4d). This observation supports the hypothesis that the delayed emission is

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

• (retention time 6.905‒6.961). One of these peaks can be assigned to the product 2a, while the other peak showed that the deacylated product 3a is formed during the transformation with subsequent oxidation by sulfur in the oxidation/reduction step to form 2,5-dihydrothiophene 1-oxide 2a′ (Figure 1, a and b

• and Scheme 6). The analysis also suggests the formation of product 2a before water and acid were added. This also indicates that the reaction proceeded through an oxidation/reduction step. UV absorption measurements of the same reaction mixture (a) and pure product 2a (b) dissolved in methanol are

• as a proton source) formed hydroperoxide D. On the other hand, competitive reversible proton movement [53] from ethanol to anion B formed deacetylated product 3a. The subsequent reduction of hydroperoxide D by the deacetylated product 3a results in the formation of hydroxy-substituted

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• of the required imine intermediate that upon reduction yields the desired product. The free base 1 was purified on normal-phase flash column chromatography, and 1·HCl was subsequently precipitated, providing a white crystalline solid (vide infra). Characterization of 25CN-NBOH·HCl (1·HCl) in the

• . Data processing (reduction, merging, and integration) using SAINT and multiscan correction for absorption using SADABS-2016-2 were performed within the Apex4 Suite [25][26][27]. Mercury 4.0 was used to prepare Figure 2a [28]. The crystal data, data collection, and data processing results are given in

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

• by substrate class (monocyclic vs fused; heterocycle vs carbocycle), all catalytic systems must still address the fundamental selectivity challenges inherent to arene reduction – chemo-, regio-, and stereoselectivity. Chemoselectivity becomes particularly demanding when reducible groups such as

• olefins or carbonyls are present, often requiring fine-tuning of the reaction conditions to prevent overreduction. Disruption of aromaticity also creates multiple potential reduction sites, and subtle electronic or substituent differences can lead to regioisomers, especially in polysubstituted or fused

• homogeneous and heterogeneous phases to achieve asymmetric complete hydrogenation of vinyl aromatics – a long-standing challenge in arene reduction (Scheme 4) [46]. By tuning the ratio of phosphine ligand to rhodium precursor, they controlled the formation of distinct catalytic species, which remained

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

• functionalization of α-fluorocarbonyl compounds via halogen atom transfer (XAT) (Scheme 9A) [27]. Conventional defluorination reactions had largely been limited to trifluoromethyl groups, which possess relatively positive reduction potentials [28][29][30][31][32][33][34]. On the other hand, reductive

• transformations of monofluoroalkyl groups have been considered difficult due to their negative reduction potentials. In contrast, the authors focused on the comparatively small bond dissociation energy (BDE) of C(sp³)–F bonds. Based on the hypothesis that this property could enable C–F bond functionalization via

• -workers and used for ketone reduction to alcohols [36]. The reaction was applicable to a range of benzyl alcohols and ethers 49a–e, delivering the desired alkanes in moderate yields. Furthermore, when substrates containing multiple C–O bonds 49d were employed, the reaction proceeded selectively at the

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

• described a ruthenium-catalyzed conversion of alkenyl triflates to alkenyl chlorides (Scheme 22C) [80]. A subsequent study from the same group demonstrated that [Cp*Ru(MeCN)3]OTf could serve as an alternative catalyst, thereby avoiding the need for in situ reduction of Ru(III) to Ru(II) by organometallic

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• reduction of the newly introduced secondary hydroxy group affords ethylmaltol (1) in four steps overall [1][4]. Different modifications of this approach have been developed, including performing the aldol addition before decarboxylation [5] or using different feedstock chemicals such as furfuryl alcohol

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

• electrochemical cell distinguishes electroorganic synthesis from traditional organic chemistry methods. Particular attention is paid to the generation of radical intermediates via the oxidation or reduction of radical precursors [40][41][42][43][44][45][46][47][48][49]. In this regard, the anodic oxidation of

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

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

• installed another exo-methylene (in the future F-ring), which would later be reduced to the methyl group at C25. Staudinger reduction and two protecting group manipulations set the stage for the formation of the piperidine (F-ring) through a Mitsunobu reaction. Hydrogenation employing Wilkinson’s catalyst

• manipulations were carried out, the double bond isomerized to position C5–C6, and a reduction was performed, all in an optimized three-step, scalable sequence. Alkylation with phosphonate reagent 36 and subsequent Horner–Wadsworth–Emmons (HWE) reaction formed ring C, followed by an enolate alkylation to forge

• substituted cyclopentenone motif 37. The authors report the reaction to favor the desired diastereomer and could further enrich the desired isomer by recrystallization. Final steps for this fragment included a 1,4-reduction of the enone motif via a copper hydride species, a Wittig reaction to install the exo

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• substitution reactions of benzo-1,3-dioxoles and benzo-1,4-dioxanes [20]. Reduction of ketones 6 and 7 with NaBH4 gave alcohols 16 and 17, which were chlorinated with SOCl2 to result in compounds 18 and 19. Treatment of the latter with the appropriate amines gave amino derivatives 20a, 20c–e, and 21a, 21c–p

• of compound 28 with 1,2-dibromoethane (29), reduction with NaBH4 (30), chlorination with SOCl2 (31) and subsequent treatment with methylamine afforded pentacyclic product 25. Reaction of bromoalkyl derivative 30 with potassium thioacetate gave acetylthio derivative 32, which was cyclized after

• removal of the acetyl group by intramolecular dehydrative thioetherification [3] to the bridged molecule 26. As regards the synthesis of compound 27, reduction of ketone 28 with NaBH4 (33), chlorination with SOCl2 (34) and treatment with 2-bromoethanol afforded 2-bromoethoxy derivative 35, which was

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

• aglycone sarmentogenin in 7 steps from 17-deoxycortisone. The synthesis features a scalable enzymatic C14–H α-hydroxylation, a Bestmann ylide-enabled one-step construction of the butenolide motif, a late stage Mukaiyama hydration, and a stereoselective C11 carbonyl reduction. Keywords: cardiac glycosides

• reactive C17 side chain including an α-hydroxycarbonyl group, a set of side reactions (e.g., reduction of the C20 carbonyl, hydrogenation of Δ4 and Δ14 double bonds, etc.) occurred under the Mukaiyama hydration conditions [30][31]. Therefore, it was necessary to alter the side chain before installing the

• . Therefore, we decided to perform the Mukaiyama hydration on advanced intermediates. Next, a K-selectride-promoted chemo- and stereoselective reduction of the C3 carbonyl of 9 was realized to solely deliver 11 in 85% yield [33]. Then, 11 was subjected to Mukaiyama hydration conditions. Under the Fe(acac)3