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

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• intermediate A (Figure 1a), in which the formerly electrophilic carbonyl carbon reacts as a nucleophilic center. In this way, the traditional reactivity profile of the carbonyl group is transiently inverted, and unconventional product classes are generated. Alternatively, addition/elimination of the NHC to a

• catalytic photoenolization/Diels–Alder (PEDA) reaction [14][15]. In this process, the NHC fragment present in the acylazolium species influences the absorption wavelength and fundamental photochemical reactivity of the C=O bond, enabling a “ketone-like” photoreaction from otherwise unsuitable carboxylic

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• functional groups that might be incorporated into co-substrates [14]. The richness of potential connective chemistry, and the availability of alternative dirhodium catalysts with distinctive reactivity, was expected to expand the structural diversity of accessible reactive probes. Herein, we describe the

• products observed by analytical HPLC. Structures and structure elucidation of intermolecular reaction products. The relevant reactivity modes are indicated by colour: O–H insertion (green); N–H insertion (blue); formal C–H insertion (yellow); and cyclopropanation (pink). Synthesis of α-diazoamide

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• . These findings provide important insights into the synthesis, cytotoxic activity, and biochemical reactivity of glycidyl esters of phosphorus acids, underscoring their potential as lead structures for further development in anticancer drug discovery and pharmaceutical research. Keywords: alkylating

• compounds 1–3 strongly indicates their ability to covalently modify nucleophilic sites in proteins. This finding underscores the potential of LSV as a rapid and effective tool for assessing alkylating reactivity, with implications for future drug development. Overall, this study offers meaningful insights

• into the synthesis, cytotoxic behavior, and biochemical reactivity of glycidyl esters of phosphorus acids. The results support their potential as reactive anticancer candidates and lay a foundation for future structure–activity relationship studies and further development in medicinal chemistry

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• catalytic asymmetric synthesis of saddle-shaped inherently chiral 9,10-dihydrotribenzoazocines via CPA-catalyzed kinetic resolution and dynamic kinetic resolution strategies [54]. By leveraging the reactivity of the aniline moiety in 9,10-dihydrotribenzoazocines 68, the CPA 16-catalyzed enantioselective

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• ]; this, despite an earlier demonstration of the superior nucleophilicity of BDC-NH2 [45]. Interestingly, this apparent reversal in reactivity was most significant with aliphatic isocyanates, while the reactivity reverted to what is expected with the use of more activated isocyanates. Subsequently, we

• rather at investigating the effect that systematic pore environment modulation has on catalyst reactivity; specifically, how lipophilization affects a condensation process like the Knoevenagel reaction. As such, it was also interesting to observe differences in the relative amount of reaction

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• -dimethylaminopyridine), affording (1S,2S)-N1,N2-bis((1R,2R)-2-(sulfonamido)-1,2-diphenylethyl)cyclohexane-1,2-dicarboxamides 4 in 32–87% yields. Electron-deficient sulfonamides 2a, 2e and 2f with both electron-donating methyl and strong electron-withdrawing trifluoromethyl and 4-nitrophenyl groups showed low reactivity

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• recognized for their high reactivity when exposed to light and are frequently employed as photo-degradable molecules. Liu described a photo-sensitized system composed of amphiphilic 9-alkoxy-substituted AnPy and p-sulfonato calix[4]arenes (SC4A) (Figure 9) [114]. SCnAs have a unique propensity to regulate

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• methoxymethyl group cleavage, O-to-N rearrangement, and isomerization of the double bond. An oxazoline ring formation in the resulting unsaturated amides provided the corresponding enantioenriched vinyloxazoline. The reactivity of the electron-deficient double bond in the vinyloxazoline was explored in several

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• this publication, the suffix denotes the number of ethylene glycol units in a single linker, for the structures of 75/6/7/8, see Figure 3a). The reactivity of 76 had previously been established in the reaction with the unsymmetric monoiodide 12 (see Figure 1e), which proceeded in 59% yield [51

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• system, a variety of other factors commonly influences both the reaction rate and the stereochemical outcome of the glycosylation reaction, including the reactivity of the acceptor hydroxy group, the effect of remote protecting groups and a balance between the nucleophilicity of the acceptor and the

• reactivity of the donor molecules [45][46][47][48]. Review Synthesis of β,α-1,1'-linked disaccharides The assembly of β,α-1,1'-linked disaccharides has traditionally been carried out using perbenzylated monosaccharide building blocks and various types of glycosyl donors, including chlorides [49], bromides

• stereospecific synthesis of β,α-linked disaccharides 69 and 71, respectively, upon reaction with the TMS-α-Glc acceptor 61 [69]. The relatively high reactivity values (RRVs) reported for 2N-Troc-protected thioglycosides suggest that introducing an electron-withdrawing substituent should not substantially

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• compound production, fundamentally involving the interaction between organic substrates and nitrating reagents. The intrinsic kinetics of nitration processes are governed by the synergistic interplay between the substrate’s molecular architecture and nitrating reagent reactivity. Distinct substrate

• classifications necessitate tailored nitrating reagent selections, giving rise to fundamentally distinct mechanistic pathways. This reactivity is exemplified by the comparative kinetic profiles: N-nitration of amines and O-nitration of alcohols – facilitated by accessible lone electron pairs – exhibit markedly

• selective mono- or di-nitration and facilitates late-stage C–H nitration of biorelevant molecules, with DFT/mechanistic studies revealing synergistic 'nitro effect' and 'methyl effect' underlying the reactivity [7]. Jia et al. developed dinitro-5,5-dimethylhydantoin (DNDMH) as an efficient arene nitration

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• immunological cross-reactivity. Moreover, pyruvate ketals are recognized as immunodominant structural features of polysaccharides, which are important in cell–cell recognition processes [13][14][15][16][17][18]. The pyruvate ketal is an important portion of immunological determinant in bacterial polysaccharides

• derivatives, enabling the exploration of the practical applications of PSA1 while simultaneously enhancing our understanding of synthetic chemistry. To simplify the synthetic process, glycosylation was facilitated by employing preactivation and the differences in acceptor reactivity. Using the p

• 10 was formed, giving 71% yield (α/β = 1:6). According to the RRV/Aka platform [44], compound 9 is a robust nucleophile, with an Aka value of 12 [45]. This high nucleophilicity favors a SN2-like mechanism, promoting β-selectivity [46]. Using the difference in acceptor reactivity and activation method