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

• 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

• forms of compounds 3n and 4n exhibited smaller HOMO–LUMO gaps compared to their protonated and deprotonated counterparts, suggesting higher reactivity (Table 5). Conclusion In summary, we have developed a straightforward approach to a Knoevenagel condensation-type reaction using ethylenediamine (EDA) as

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

• , the bis-epoxy ketone exhibited distinct reactivity under ring-opening conditions compared to mono-epoxy substrates, presumably due to steric constraints. Leveraging the directing ability of the C10 hydroxy group, stereospecific Mukaiyama hydration of the C6–C7 double bond was achieved, furnishing

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

• inaccessible (Scheme 5) [41]. We assumed the steric hinderance of the Boc protecting group might have a great impact to the reactivity of ketone. Investigation along this line is currently on the way. Conclusion In summary, we have streamlined the rapid construction of the core perhydrofuropyran skeleton of

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• reactivity of this family of pentacyclic aromatic heterocycles towards N-benzylation and the antimicrobial properties of such resulting quaternary ammonium compounds are ongoing. Examples of polycyclic aromatic heterocycle structures: phenanthridine (left), 1,5-naphthyridine (center), and 1,9-phenanthroline

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• addition to potassium thioacetate, the reactivity of ester 1 was investigated with other related S-nucleophiles, such as potassium ethyl xanthate (KSC(S)OEt), sodium diethyldithiocarbamate (NaSC(S)NEt2) as well as thioacetamide in the presence of K2CO3 and Na2S2 (Table 1, entries 2–5). In each case, the

• . Conclusion In summary, this study reveals an unusual and previously poorly understood reactivity of 3-nitrothiophene-2,5-dicarboxylate toward sulfur-containing nucleophiles such as potassium thioacetate or thioacetamide, which resulted in the efficient formation of both bis(thiophen-3-yl) sulfide and

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

• challenging due to the inherently higher reactivity at the C3/C6 positions. In this study, we report a palladium-catalyzed, directing group-assisted, regioselective C1–H nitration of carbazoles. The protocol features a removable directing group and is amenable to gram-scale synthesis. This strategy provides a

• reagent resulted in complete loss of reactivity (Table 1, entry 12). Further, extending the reaction time had no significant effect on the yield (Table 1, entry 13). Finally, our investigation using various 3d transition metal catalysts such as Ni(OAc)2, Cu(OAc)2, and Co(OAc)2 in place of Pd₂(dba)3 did

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

• , which indicates that steric hindrance at C2 has a limited effect on the reactivity. However, when the steric hindrance of the protecting group was increased by replacing –Cbz with –Boc, the activity of the PET reaction decreased, which resulted in a lower yield of 10f (45%). In the case of substrate 9g

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

• turned out to be unsuccessful as the reaction seemed to achieve an equilibrium, with some amount of hemiacetal left. Generally, it was observed that the trifluoroacetimidates were somewhat more sensitive to flash column chromatography, suggesting a higher reactivity compared to the trichloroacetimidates

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

• equilibrium lie outside the carbohydrate ring system. Consideration of such effects is essential to rationalize the reactivity of structurally complex and densely protected carbohydrate compounds. Keywords: benzoylated galactofuranosides; DFT; DLPNO-CCSD(T); pyranoside-into-furanoside rearrangement

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

• excellent conversion rates (up to 95% yield) and high enantioselectivity (up to 96% ee). Notably, isoquinoline derivatives containing polycyclic naphthalene moieties or ortho-substituted phenyl groups also demonstrated good reactivity and compatibility. DFT calculations indicated that the C–Se bond

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

• of reactivity, they are environmentally sustainable alternatives to heavy metals. The advantage of hypervalent catalytic systems based on iodine lies in their reusability [63]. The oxidative contraction of the tetralone cycle 117 depended on the stoichiometric amounts of iodine(III)-based chiral

• simple building blocks [72]. The main feature of light-induced transformations is the involvement of electronically excited states that occur during photon absorption, leading to the formation of reactive intermediates causing significant changes in chemical compound reactivity. As a result, light energy

• compounds [78][79][80][81][82]. The work of Davis, Derksen and co-workers [83] presents interesting results on the use of UV light to study the reactivity of bicyclic divinyl ketones and the dependence of photochemical reaction products on wavelength. Under anhydrous conditions, irradiation of divinyl

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

• reactivity of this double bond can pose significant challenges, particularly in cycloadditions or other organic transformations that necessitate extended cycloaddition processes and elevated temperatures. With a boiling point in excess of 260 °C, methyl laurate has the potential to function as a green

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

• developed an approach to assemble the bicyclic skeleton of vibralactone (6) utilizing an intramolecular alkylidene carbene C–H insertion as key step. The insights gained from this study illustrate how diverse reactivity patterns and electrophilic characteristics of alkylidene carbenes influence ring closure

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• synthesis, the 3-chloropyridine 68 used in the Dai synthesis exhibited much lower reactivity compared to the 3-bromopyridine 55 used in the Tsukano synthesis. Thus, a set of new reaction conditions was needed. To solve this reactivity issue, a protocol developed by Stoltz et al. in their jorunnamycin

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

• , 108d) underwent the desired photochemical reaction (Scheme 13b), yielding spiroacetals 109a, 109b, and 109d following CAN (cerium(IV) ammonium nitrate) oxidation. In contrast, C7-methoxy-substituted analogs (108c, 108e) remained unreactive. Reactivity correlated with UV–vis absorption profiles

• : reactive substrates exhibited λmax < 460 nm (yellow-orange), whereas unreactive ones showed λmax > 460 nm (dark red-purple). This suggests insufficient excitation energy for Norrish type-II hydrogen abstraction in the latter. Such chromophore-dependent reactivity provides critical insights for designing

• less favorable pathway compared to the previously employed 1,5-HAT. Initial feasibility studies revealed that the non-brominated substrate exhibited poor reactivity in the photochemical 1,6-HAT reaction (Scheme 14), as its unreactive conformer J dominated the equilibrium. In contrast, the brominated

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

• morpholine via an aza-Michael addition and condensation (Scheme 3). It was envisaged that the β-amino group could act as a stable functional group resulting in Baylis–Hillman-like reactivity. An extensive survey of reaction conditions using Selectfluor and N-fluorobenzenesulfonimide (NFSI) as the sources of

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

• tolerance, and scalability [80]. Electrochemical methods offer the opportunity to tune reaction conditions by controlling parameters such as potential, current, electrode, and electrolyte [81], providing a sophisticated platform for attaining optimal reactivity. A variety of catalytic strategies can be

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

• /cycloisomerization sequences. In 2019 and 2020, Liu and co-workers achieved pathway-controlled cyclization–isomerization of tryptamine-ynamides using ligand-influenced silver catalytic systems (Scheme 19) [27][28][29]. To circumvent decomposition caused by the inherent high reactivity of ynamides under catalytic

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

• avoiding excess reagent, and simplifies purification and scale-up. With the most suitable reaction conditions in hand, the substrate scope was examined. First, the reactivity of different aryl bromides with phenylhydrazine (1a) to form non-symmetric azobenzene was explored (Scheme 1). Most of the

• , para-substituted hydrazines such as p-(trifluoromethyl)phenylhydrazine (1b) and p-chlorophenylhydrazine (1c) reacted efficiently with 2-bromotoluene to deliver the corresponding azobenezenes 4a and 4d in 78% and 37% yield, respectively. Notably, 2-tolylhydrazine (1d) exhibited good reactivity, yielding

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

• biomass shows how renewable carbon sources can replace non-renewable chemicals in important industrial processes [18][19][20]. Many, if not most, biobased platform molecules contain carbonyl groups. Carbonyl compounds have unique electrophilic and nucleophilic reactivity which make them central players in

• organic synthesis. Therefore, synthetic chemists can base strategies on the existing reactivity of carbonyl compounds for defining novel routes converting biobased platform molecules containing carbonyl groups to prepare fine organic chemicals [21][22]. Following this approach, researchers can obtain

• viewpoint by focusing on the reactivity of biobased platform molecules containing carbonyl groups. This review, which does not pretend to be comprehensive, attempts to highlight the central role of carbonyl-containing biobased platform molecules notably those having a C2 to C6 backbone shown in Figure 1

Multicomponent reactions IV

• Thomas J. J. Müller and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163

• , even allow changes in conditions from one step to the next. In essence, MCRs embody a reactivity-driven concept [4] within the broader family of one-pot methodologies. This thematic issue on multicomponent reactions continues the previously published editions from 2011 [5], 2014 [6], and 2019 [7] and

• of countless molecules, spanning small compounds to microstructures. The amphiphilic reactivity of isonitriles appears virtually limitless, extending well beyond classical Ugi-type reactions into other MCR contexts. At the same time, MCRs not based on isonitriles are gaining increasing momentum, with

• focused Reviews on heterocycles, reactivity patterns, and the role of MCRs as enabling tools at the interface with biosciences underscore the timeliness and enduring elegance of this powerful and concise concept in molecular synthesis. As the guest editors of this thematic issue, we would like to thank

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• bioinspired synthetic approach [44]. Initially, we prepared a bicyclic precursor similar with toussaintine C to react with α-phellandrene to mimic the bioinspired Diels–Alder reaction, which, however, showed no reactivity due to the strong steric hindrance. To decrease the steric effect, we finally used

• invented. Moreover, bioinspired total synthesis involving visible light and enzymes are new significant trends in this field, and these techniques have demonstrated great power in achieving unprecedented selectivity and reactivity. Since nature still prevails in rapid generating molecular complexity and

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• possibility of synthesizing various heterocyclic systems such as quinazolines [25], diazepinones [25][26], quinoxalinones [27], diazocinones [28], and imidazolines [29] due to the exceptional reactivity of the azido group. However, the use of azido amines in the Ugi reaction together with oxoacids, which have

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• the reagents of choice for arylation reactions, where an umpolung of reactivity is required [1]. Arylations employing diaryl-λ3-iodanes can be performed under metal-free [2] or metal-catalyzed conditions. For alkyne arylations [Cu] [3] or [Pd] catalysis [4][5][6] is typically employed. Internal

• by the diene/indene 10a/11a molar ratio (determined by NMR). Among the tested diaryl-λ3-iodanes, only those containing a triflate anion showed reactivity. PhMesIOTf (I-1) and Ph2IOTf (I-2) showed comparable results in terms of diene yield, however, the symmetrical iodane I-2 displayed better

• , partial degradation of the starting material 7a was also observed. Among the tested solvents, EtOAc gave the best results (Table 1, entries 1–3, 7–18). As for reaction catalysts, Cu(I) salts demonstrated far better reactivity than Cu(II) salts, likely because the reaction proceeds via the Cu(I/III