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

• . Eventual change of the two PNB- with TBDMS-protecting groups yielded 45 in 58%. Notably, by this technique, the central pyran motif was assembled in one step and required only the stereoinformation of 42`s alcohol unit, while in former works two individual steps and the use of expensive metal catalysts

• competitive reaction sequence for the large-scale process currently applied by Eisai [66]. Furthermore, this method stands out for its cost-efficiency, since only an enantiomeric pair of ruthenium catalysts is needed in addition to other standard chemicals. A similar building block as from Kaghad and co

• field of the synthesis of 1. This is especially observable for the synthesis of the 4 heterocyclic key fragments or intermediates obtained during the Eisai process. Here, the major progresses can be registered in terms of enhancing the sustainability of pathways through the removal of metal catalysts

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• studies have further broadened the synthetic toolbox for remote biaxial chirality. Du and co-workers designed a series of chiral phosphoric acid catalysts derived from protected axially chiral diols 13, employing a boronic acid-mediated coupling strategy to construct remote biaxially chiral phosphoric

• ligands (Scheme 3) [44]. The resulting catalysts 18 demonstrated remarkable efficiency in the asymmetric transfer hydrogenation of quinoline derivatives. Along similar lines, Zhang and co-workers introduced an additional axial chirality element into a ligand framework, affording a pair of diastereomeric

• utility of machine learning in predicting the synthetic feasibility of ligands. By integrating a wide range of Pd catalysis data with limited Ni/Sadphos data through a co-modeling approach, this work pioneered a few-shot learning strategy for the design of molecular catalysts. Transformation from central

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• readily available. Additionally, Xiang et al. [17] and Jew et al. [18] reported asymmetric syntheses of taxifolin, which suffer from long-step operation and the use of complicated and expensive metal-ligand catalysts. Currently, the most widely used chemical method is the synthesis of trans-(±)-taxifolin

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• remains a significant and persistent challenge in synthetic chemistry [41][42][43][44]. Classical approaches for activating non-activated amides typically rely on transition-metal catalysts acting as Lewis acids, which coordinate to the carbonyl oxygen and enhance electrophilicity (Scheme 1d). However

• can also serve as efficient catalysts for activating amide C–N bonds. SanMartin et al. investigated a palladium-catalyzed transamidation of non-activated amides 5, 27–29 with benzylamines, in which molecular oxygen acted as the palladium-activating agent (Scheme 6) [50]. Notably, high yields of the

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

• components of many high-tech materials, such as energy storage and organoelectronics devices [1][2][3][4][5][6][7][8], catalysts [9][10], bioactive coatings and nanoparticles [11][12], organic radical contrast agents (ORCAs) for magnetic resonance imaging (MRI) [13][14], etc. For these applications, numerous

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• with α,β-unsaturated esters, such as (E)-3-(3,4-dimethoxyphenyl)acrylic acid esters 3 (see Supporting Information File 1) exemplified by compound 4. Different solvents and catalysts, both acidic and basic, were screened at room temperature, including refluxing in pyridine with piperidine, but the

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• utilization in metal-chelating agents, flame retardants, and catalysts [3][6][7][8][9][10][11][12][13][14]. However, these applications involved the use of either phytic acid itself or its derivatives. Our group has previously reported a method for synthesizing diaryl phosphates using phosphoric acid as the

• [22] and as insecticides [23]. Particularly, phosphate diesters are among the most important synthetic catalysts, such as the Akiyama–Terada catalyst that serves as a chiral Brønsted acid catalyst [24][25] and promotes a variety of stereoselective reactions. Phosphate diesters also catalyze the ring

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• catalysts [33]. A domino reaction was developed, beginning with a PPS L2-catalyzed Michael addition of phosphine oxides 7 to nitro-substituted oxa[5]helicenes 6, followed by a copper-promoted aromatization. This sequence efficiently produced phosphorus-containing oxa[5]helicene derivatives 8 in high yields

• nanoscale phenomenon that requires the design of advanced catalysts to achieve high enantioselectivity. Although the parallel approach is still in its infancy, it holds immense promise. With the continued and widespread efforts of synthetic chemists, we anticipate that the existing challenges will be

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• , such transformations remain synthetically challenging. This is primarily due to the well-known Mukaiyama-type oxidation, wherein sulfenamides serve as redox catalysts for NBS- or NCS-mediated oxidations of alcohols to aldehydes or ketones (Scheme 1b, top) [38][39][40][41][42]. Under such oxidative

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• synthesized and screened in asymmetric Mannich reaction. The reaction of aromatic imines with malonates in the presence of amino acid-derived catalysts gave Mannich adducts in very high enantiomeric purities (up to 98% ee). It is proposed that a network of hydrogen and halogen bonds with Lewis bases, together

• led to the use of multifunctional catalysts of “homocooperativity,” where multiple units of the same catalyst perform different but complementary roles [17]. These catalysts employing noncovalent interactions via hydrogen bonds and also possess Lewis basic and π–π-interaction sites have been highly

• reactions to imines [27]. The model reaction was performed in the presence of various types of catalysts (Figure 1). The syntheses of the catalysts are described in Supporting Information File 1. All catalysts used are amides containing tertiary amino groups, which are needed for the activation of the

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

• 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

• -art systems depend on expensive transition metals such as platinum, ruthenium, or palladium, inflating the cost of large-scale applications. In addition, precious-metal catalysts often display poor selectivity, while heteroatoms in heteroarenes – acting as Lewis bases – tend to coordinate to the metal

• heterocycles exhibit strong Lewis basicity, potentially complexing and deactivating catalysts. Consequently, the catalytic hydrogenation of six-membered aromatic heterocycles such as pyridine often requires the introduction of substituents or activation of the aromatic heterocycle to facilitate hydrogenation

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

• and accelerating the whole process. Zr-mediated catalytic radical reactions In recent years, numerous chemical transformations employing photoredox catalysts in combination with catalytic amounts of zirconium complexes have been reported. In this section, representative examples of such reactions are

• for further development in this area. In 2022, Ota and Yamaguchi et al. reported the zirconocene-catalyzed ring-opening of epoxides using Cp₂Zr(OTf)2·THF (Scheme 5) [4]. Traditionally, such transformations are carried out with low-valent titanium catalysts, which typically proceed via more substituted

• zirconocene catalysts using substrates 23l–n. In both cases, the regioselectivity was found to be reversed. With titanocene, the reaction proceeds through the more stable, substituted radical, whereas with zirconocene, the high oxygen affinity of zirconium is the key factor driving the opposite

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

• stereocontrolled olefin metathesis with molybdenum catalysts to access trisubstituted alkenes including alkenyl chlorides (Figure 3H) [39]. Two recent reviews by Lu [40] and Nishiwaki [41] provide overviews of current developments in the hydrochlorination of alkynes, highlighting emerging catalytic strategies

• rapidly decomposes into catalytically inactive species 288 and 289 (Scheme 55). Consequently, metathesis with trans-chloroethylene presents a significant challenge. Grela was the first to demonstrate that metathesis is indeed feasible using phosphine-free catalysts [189]. The formation of the desired

• also be applied to hydroxy- or carboxylic acid-containing olefins by adding 1.1 equivalents of HB(pin) to perform traceless protection of these functional groups, which are otherwise incompatible with molybdenum metathesis catalysts. The in situ-generated boronic ester is conveniently cleaved by silica

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• -substituents; α,β-unsaturated carbonyl compounds; Introduction Hypervalent iodine compounds exhibit a range of bonding patterns which making these compounds powerful reagents or catalysts for a number of organic transformations [1][2][3][4] – oxidation of alcohols [5], epoxidation of alkenes [6], oxidative

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

• 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

• ], diammonium phosphate (DAP) [43], and tetrabutylammonium bromide (TBAB) [44]. Organic bases like morpholine [45], triethylamine [46], ethanolamine, and piperidine [47] and heterogeneous catalysts from Cu [48], Ti [49], and Zn [50] metal compounds have also been used. Common solvents are ethanol [51], toluene

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

• , Michael additions, cycloadditions, domino reactions, cascade annulations, Diels–Alder reactions, and Michael–Stetter reactions, to name a few [31][32][33][34][35]. Notably, previous reports have demonstrated that the utility of chiral N-heterocyclic carbene (NHC) catalysts permits contracting asymmetric C

• –C, C–HA bond-forming reactions [36][37]. These chiral NHC catalysts, used to access enantiopure alcohol/amine derivatives, particularly 2° and 3° alcohols/amines, are significant structural motifs in numerous drugs and natural products and have found widespread synthetic applications in medicinal

• continued integration of this versatile photocatalytic platform with sustainable methods such as visible-light harvesting and the use of earth-abundant catalysts is expected to further enhance its impact across diverse research fields, including chemical biology, pharmaceuticals, agrochemicals, polymers

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

• 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

• catalysts that could promote the proposed PET reaction of 9a on the basis of our previous results [15]. The reaction was performed in MeCN in the presence of photocatalysts under blue light-emitting diode (LED) irradiation at 30 °C. The results are listed in Table 1. Catalysts I [28], II [29], and III [30

• ] 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

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

• Atropisomers are not only prevalent in biologically active natural products and pharmaceuticals, but they have also garnered increasing attention for their effectiveness as ligands and catalysts in the field of catalytic asymmetric synthesis. Asymmetric catalysis serves as a key strategy for the

• compounds can participate in asymmetric synthesis reactions and construct chiral molecules with specific stereoconfiguration, which is particularly critical for drug synthesis [9]. In the field of organic catalysis, chiral organic selenium-containing compounds can be used as chiral ligands or catalysts to

• (Scheme 4). In 2025, Yang, Lu, and co-workers employed bifunctional catalysts, including chiral thiourea derivatives or chiral phosphoric acid, to activate alkynes and selenols through multiple hydrogen-bonding interactions, thereby achieving an enantioselective hydroselenation of alkynes [22]. All

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

• [52] achieved high regioselectivity and stereospecific construction of contiguous all-carbon quaternary centers through an oxidative ring contraction of cyclic α-formyl ketones by the action of H2O2. This reaction is easy to perform, environmentally friendly, and does not require expensive catalysts

• products of epoxide ring opening. It should be noted that the position of the epoxy ring in the 6-membered ring has a major influence on the composition of reaction products. Catalysts only affect the yield of the reaction. A striking confirmation of this is the work of Berteina-Raboin and co-workers [87

• 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

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

• optimized [3 + 2] cycloaddition conditions. The primary strategy for the selection of these compounds as catalysts is predicated on their capacity to function as H-bond acceptors and/or H-bond donors. As has been documented in previous research, imine-based templates or [2]rotaxane that possess an amide

• in Table 1, entry 9. As illustrated in Table 5, the product yields obtained from the reactions are presented alongside the observed cis/trans diastereoisomer ratios in the presence of the respective catalysts. However, upon examination of the 1H NMR spectra of compound 3a synthesized in the presence

• 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

Adaptive experimentation and optimization in organic chemistry

• Artur M. Schweidtmann and
• Philippe Schwaller

Beilstein J. Org. Chem. 2025, 21, 2367–2368, doi:10.3762/bjoc.21.180

• human–AI synergy emerges repeatedly. The computational design of asymmetric catalysts by Ferrer et al. demonstrates how AI can accelerate discovery while relying on chemical principles to guide the search space [14]. The most successful approaches combine the rapid exploration capabilities of AI with

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

• ingenuity lies in utilizing the inherent conformational constraints of the substrate instead of external chiral catalysts, which not only simplifies the reaction system but also solves the challenge of precisely controlling contiguous chiral centers in polycyclic systems. Conclusion This review

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

• enantioenriched catalysts ranging from chiral organometallic complexes to organocatalysts (small organic molecules) have been designed, synthesized, and successfully used in several organic transformations [1][2][3]. Despite these advances, catalytic methods involving radical intermediates were very rare until

• 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

• catalysts. The drawbacks of chiral Lewis acids have been overcome to an extent using organocatalysis. The use of photochemistry to generate radicals by light-induced electron transfer has resulted in elegant enantioselective radical transformations. Several transition-metal photocatalysts [9] and organo

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

• substrate class. Through mechanistic-guided modulation of catalysts, solvents, ligands, and angle strain, this approach achieves unprecedented reaction pathway control while demonstrating superior temporal and step efficiency compared to conventional methods. The work establishes a sustainable framework for

• components such as solvents, catalysts, ligands and so on. Unlike traditional “one-to-one” reactions, pathway-controlled “one-to-many” transformations synthesize multiple products from single intermediates, dramatically reducing preparation time and reagent requirements (Scheme 1b). As an exceptionally

• ligands could enhance catalytic activity and efficiency while enabling fine control over chemo-, regio-, stereo-, and enantioselectivity of reactions. Ligands enhance both the thermal/chemical stability and solubility profiles of catalysts in specific reaction media. Thus, ligands function as a regulatory