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

• saturation the aromatic ring facilitates synthetic chemists to efficiently synthesize natural products with complex three-dimensional structures. Recent advances in catalyst and ligand design have enabled unprecedented progress in the catalytic hydrogenation of (hetero)aromatic systems. Quinoline

• limitation requires the design of catalysts that achieve precise electronic complementarity, enabling selective activation across a broad spectrum of aromatic compounds (Scheme 2) [32]. From the standpoint of scalable synthesis, catalyst cost is a major bottleneck in aromatic hydrogenation. Most state-of-the

• transformation into a broadly enabling strategy in complex molecule synthesis, yet a unified perspective connecting recent methodological advances with their strategic applications in the total synthesis of natural products remains lacking. Although several reviews discuss catalyst development for (hetero)arene

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

• Schwartz’s reagent to furnish product 4d. In 2017, Kishi et al. reported a radical-based ketone synthesis employing zirconocene and a nickel catalyst (Scheme 2A) [9]. Traditional anion-based ketone syntheses (e.g., Grignard or RLi reagents) are often unsuitable for complex molecules due to the strongly basic

• a photosensitizer, together with compound 22 as a sacrificial reductant, in the dimerization of benzyl bromide (19). The desired dimerized product 20 was obtained in 40% yield. This study highlights the potential of zirconium complexes as a photoredox catalyst, pointing to promising opportunities

• experiments, coordination of thiourea 26 to the Zr center was suggested. This effect is considered to have tuned the reactivity of the Zr-catalyst, thereby having a positive effect on the reaction process. Finally, the regioselectivity of epoxide ring opening was compared between low-valent titanocene and

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

• ). In 2006, Apotex reported the synthesis of alkenyl chlorides using POCl3 in the presence of triethylamine and a copper catalyst (Scheme 16) [69]. The preparation of compound 84 is of industrial significance due to its application in the synthesis of terbinafine (86), an antifungal agent. The reaction

• that were irreversibly adhered (Figure 6, oval stirring bar left a mark in the solid polymer). Various catalyst loadings of CuCl (5–20 mol %) were evaluated, with 15–20 mol % required to achieve useful yields of 9 within several hours (Figure 7). Mechanistic analysis proved challenging, as the catalyst

• 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

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

• 94% yield using CPhos-Pd-G3 as the palladium pre-catalyst (Scheme 1) [31]. However, under the same reported conditions only the unreacted starting material was recovered. In an isolated example, C-7 allylation of 7 was reported via a Stille coupling protocol to give 8 (Scheme 1) [32]. As an

• alternative approach to C-7 functionalization of Nα-Boc-tryptophan methyl ester, we chose a CH activation protocol [33]. Treatment of N1-Piv-Nα-Boc-tryptophan methyl ester (10) with but-3-en-2-one (MVK) in the presence of [RhCp*Cl2]2 catalyst according to Ma et al. [34] led to the 7-(3-keto-1-butyl)-alkylated

• 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

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• without catalysis or using triethylamine–acetic acid as a bifunctional catalyst (Scheme 2). The reactions with alkyl methyl ketones 2b,c in 1,4-dioxane without catalysis led to the formation of a mixture of octahydropyrido[1,2-a]pyrimidinones 4b,c and hexahydrooxazolo[3,2-a]pyridones 5b,c, but with a

• catalyst, the cis,trans-isomer is preferentially formed, whereas dual acid-base catalysis favors the formation of the other cis,cis-diastereomer. The obtained hydrogenated oxazolo- and pyrimido-condensed pyridones are of interest for biological testing, which is confirmed by the discovery of an antiviral

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

• enantiomeric excess of 92%. This asymmetric hydrogenation included a novel iridium catalyst featuring a chiral SpiroBAP (spiro bidentate aminophosphorane) ligand, which has been developed previously by this group and was now successfully applied in this synthesis [36]. A silver-catalyzed, enantioselective

• to abstract the chloride of the [Rh(cod)Cl]2 catalyst, forming a cationic rhodium complex in situ, while diethyl fumarate acted as a hydrogen acceptor. Double bond isomerization, ketone reduction and deprotection of 73 furnished veratramine (13). This Diels–Alder strategy concluded the synthesis of

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

• typical Mukaiyama hydration conditions [30][31][32] to install the C14 β-hydroxy group. However, only a trace amount of the undesired C14α-hydroxylated product 10 was obtained. Additional optimizations regarding the transition-metal catalyst, hydrogen source and solvent all failed to improve the results

• -catalyzed anaerobic conditions [30], 11 was transformed into the C14 hydroxylated intermediate 12 as epimeric mixture in 42% yield and dr = 1:5, among which the undesired 14α-hydroxy epimer was the major component. Interestingly, the use of Co(acac)2 or Mn(acac)2 as the catalyst [31][32] instead of Fe(acac

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

• different products were obtained), delivers excellent yields (up to 99%), and requires low catalyst loading (10 mol %). This new approach was successfully applied to the synthesis of eight novel imidazo[1,2-a]pyridine–thiazolidinone hybrids in good to excellent yields (66–99%). A spectroscopic study of

• condensation-type reaction between aromatic aldehydes with rhodanine or thiazolidine-2,4-dione [39]. Various protocols have been reported employing diverse catalyst systems and reaction conditions. Common catalysts include inorganic bases such as sodium acetate (NaOAc) [40], urea/thiourea [41], NaOH [42

• drawbacks, including long reaction times, harsh conditions, low to moderate yields, tedious work-up procedures, use of environmentally hazardous solvents, high catalyst loadings, toxic residues, and the need for specialized apparatus. To address these limitations, alternative methodologies have been

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

• positive to enable SET oxidation by photoexcited 4CzIPN. The authors described that the reduction potential of the photoredox catalyst (PC = 4CzIPN) was moderately low [Ered(IrIII*/IrII) = +0.66 V vs SCE in MeCN], and the silylboronate 13 permitted the formation of the silyl radical C under mild oxidation

• catalyst. The anticipated meta-acylation product 32 was achieved through highly selective C(sp3)–C(sp3)-radical–radical cross-coupling between the cyclohexadienyl radical C and the benzyl radical species F, formed via single-electron reduction. This photochemical method overturns the traditional ortho and

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

• the same pot to give 72. Isomerization of the allylic methyl ether to an enol methyl ether was achieved using Crabtree’s catalyst in refluxing THF. Subsequent ketalization with the primary alcohol yielded the bridged ketal 73. A Schenck ene reaction on 73 induced the second olefin isomerization

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

• reaction with allyltributylstannane, yielding compound 40. After isomerization of the C11 allyl double bond and introduction of a C6 isobutenyl group, the resulting diene 42 underwent RCM catalyzed by the Hoveyda–Grubbs catalyst to form the pentacyclic skeleton 43, thus completing the C ring of the natural

• deprotection and ester hydrolysis produced carboxylic acid 101, which upon oxidative dearomatization yielded dienone 102, thus completing the D-ring. Regioselective epoxidation to 103 and reduction (using Adams' catalyst) through intermediate 104 gave lactone 105. A retro-oxa-Michael/intramolecular

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• substrate, using silver nitrate as the nitrating agent (Table 1). After detailed optimization studies, we found that the treatment of 1a with AgNO3 in the presence of Pd2(dba)3 as the catalyst in 1,4-dioxane afforded the desired C1-nitrated product 2a in 69% isolated yield (Table 1, entry 1). Product 2a was

• failed to enhance the product 2a yield (Table 1, entry 10). Attempts to optimize the reaction temperature did not yield improvements either (Table 1, entry 11). Control experiments confirmed that both the palladium catalyst and AgNO3 are essential for the reaction to proceed, as omission of either

• palladacycle 6 as the catalyst, and the desired nitrated product 2a was obtained in 48% yield (Scheme 5c). This result supports the involvement of palladacycle intermediate 6 in the catalytic cycle. Proposed mechanism Based on our experimental results and related literature precedents [68][69][74][75][76][77

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• ] gave the desired product 10a, with catalyst I giving the best result (Table 1, entries 1–3). The necessities of irradiation and the presence of a photocatalyst were also defined (Table 1, entries 4 and 5). However, use of the other tested catalysts did not give the desired product under the reaction

• conditions (see Supporting Information File 1 for details). Next, we evaluated the effects of different solvents on the production of 10a in the presence of catalyst I. Changing the solvent to MeOH, tetrahydrofuran (THF), and dichloromethane (DCM) resulted in decreased yields and substrate conversions, and

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• trichloroacetimidates K2CO3 was effective for the synthesis of β-acetimidates [26], whereas polystyrene-supported DBU [27] was found to be less effective and DBU was therefore the preferred catalyst. The synthesis of perbenzylated α-glucosyl trifluoroacetimidate 3 proceeded in 52% yield on a preparative scale, with DBU

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• (Figure 1) [19]. The introduction of an alkyl or aryl substituent in the anomeric center prevents free interconversion between pyranose and furanose forms; however, this transformation can still occur under specific conditions, typically in the presence of an acid catalyst. Even under such conditions, the

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

• pathway. In both pathways, the active chiral rhodium catalyst is regenerated through a silver salt-mediated recycling, with Ag–SePh being formed as a byproduct (Scheme 2). 2. Catalytic atroposelective synthesis of selenium-containing atropisomers by spontaneous selenosulfonylation of alkynes Vinyl

• or cationic species. In 2019, Qin and co-workers reported a methodology enabling the difunctionalization of alkynes through selenosulfonylation of a VQM intermediate under mild reaction conditions [20]. This racemic transformation proceeds without the need for any catalyst or additive, and the

• reaction yielded the desired product at room temperature with high regioselectivity and stereoselectivity (E/Z ratio >99:1). Notably, when chiral catalyst (cat.1) was used, the reaction afforded the axially chiral product 9 in 43% yield with 84% ee. The proposed mechanism proceeds as follows. Catalyst cat

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

• ] using Co(II) catalyst 113, in the presence of PhSiH3, TsCl in MeOH resulted in the formation of a cyclopentenone derivative 111 with a yield of 43% and a small amount (<5%) of cyclopentenone derivative 112. The remaining mass balance consisted mainly of the recovered starting material. Demethylation of

• (±)-terretonin L (109) as the main product with a yield of 46%. Radical hydrochlorination of olefin 110 under more powerful oxidizing conditions (Co(II) catalyst 113, N-fluoropyridinium salt (F+) 114), resulted in the formation of cyclopentenone derivative 112 with a yield of 90%. Demethylation of the latter led

• completed by converting the exocyclic methyl ester 144 to an aldehyde145 using a one-pot DIBAL-H/Dess–Martin procedure followed by the removal of TMS protecting group using a stoichiometric Wilkinson’s catalyst (Scheme 25). The authors noted that, in the final stages of reduction and oxidation, yields were

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• functionality have been observed to exhibit notable trans diastereoselectivity in the context of cycloaddition reactions [130][131][132][133][134][135]. For this purpose, equivalent amounts of nitrone 1a and maleimide 2a were reacted with 5 mol % catalyst (Table 5) under the cycloaddition conditions determined

• of the relevant catalysts, it was found that these catalyst molecules had no significant effect on the cis/trans diastereoisomer distribution. Conclusion In conclusion, the present study reveals that methyl laurate is an excellent biocompatible solvent candidate for [3 + 2] cycloaddition reactions

• (cis + trans isomers). Catalyst survey for the synthesis of 3a (cis + trans isomers). Supporting Information Supporting Information File 4: Characterization data, copies of NMR spectra, additional Table and Figures. Funding We gratefully acknowledge the Bursa Uludağ University Scientific Research

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• -fumaramide showed stereoselectivity. Upon photoswitching to the cis isomer, the macrocycle moved to the thiodiglycolamide site, which disrupted its ability to catalyze the reaction, leading to the loss of stereoselectivity. This work represents the first evidence of a light-responsive interlocked catalyst

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

• , followed by diastereoselective α-alkylation, produced 38. A Wittig reaction and subsequent deketalization converted the ketone in 38 to the terminal alkene 39, allowing for subsequent sequential chemoselective hydrogenations: first, hydrogenation of the exo-olefin using Wilkinson’s catalyst proceeded with

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• reaction of methylene-bridged glycoluril dimer G2BCE with aromatic walls W1–W4 conducted in trifluoroacetic acid (TFA) as both solvent and acid catalyst. The new hosts G2W1–G2W4 were obtained in 28, 33, 59, and 62% yield, respectively, after washing and recrystallization processes. Hosts G2W1–G2W4 are

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

• include the use of transition metals or photoredox catalysts. In photoredox catalysis, radical generation often involves single-electron transfer (SET) to or from a photoexcited state of a photoredox catalyst, usually a metal complex or organic molecule. Two other notable strategies for radical generation

• obviating the need for both enantiomers of the ligand. Although chiral Lewis acid-mediated radical reactions were groundbreaking, they suffered from major disadvantages: (a) high catalyst loadings (stoichiometric or sub-stoichiometric), (b) large amounts of the radical initiator, (c) the need for a large

• applied in the development of enantioselective polyene cyclizations, which demonstrated the power of the catalytic strategy. In the presence of a chiral amine catalyst 16 (Scheme 3) and the mild oxidant Cu(OTf)2, polyenes with a terminal aldehyde group underwent intramolecular cyclizations affording

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

• systematically regulating reaction parameters (solvent, substituent, ligand, catalyst) in 1,n-enyne cyclizations, enabling efficient "one-to-many" transformations that drastically reduce synthetic steps and resource consumption. Review Solvent-controlled cyclization of 1,n-enynes Solvents play a multifaceted

• solvent-controlled selective syntheses of two polycyclic compounds (Scheme 6) [13]. Using PdCl2 as the catalyst and DMF as the solvent, substrate 22 underwent a 6-endo-dig cyclization and subsequent enone insertion, forming a palladium–carbon bond intermediate. Protonolysis yielded isocoumarin-fused

• afforded selective access to four indole derivatives through modulation of the alkyne's terminal substituents and nucleophile type (Scheme 14) [21][22]. The gold(I) catalyst activated the unsubstituted terminal alkynes to initiate a 5-exo-dig cyclization, generating a spiro[indoline-3,3'-pyrrolidine

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

• synthesis [18][19][20][21]. Sudhakara et al. described the advantages of using bismuth nitrate as catalyst in the synthesis of hydrazones and in the one-pot Fischer synthesis of indoles from ketones and hydrazines [22][23]. Adopting this method, hydrazone intermediates 7a–j were obtained by treatment of

• hydrazino derivatives 5a,b with ketones 6a–e in the presence of bismuth nitrate pentahydrate catalyst in refluxing methanol with good to excellent yields (method A, step 1). As regards cis–trans isomerism, compounds (E)-7a and (E)-7f were isolated in high yields (94% and 84%, respectively), however, in the

• were previously used for the synthesis of 7-nitroindole derivatives: heating in polyphosphoric acid (PPA) at 80 °C [24][25]. However, our attempt was not successful. Experiments with zinc chloride, the most commonly used Lewis acid catalyst in Fischer indole syntheses, also failed under various

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• access triazole-fused and tetrazole-tethered benzodiazepines 7 via Ugi–azide/intramolecular click reaction under Cu-catalyst-free conditions. The 4-CR Ugi–azide reaction was modified to be a one-pot two-step reaction process to address functional group compatibility issues. By using 2-isocyanoacetate