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

• [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

• of chirality. Molecules with helical chirality impart a crucial role in several biological phenomena as well as in modern materials applications. Classically, the generation of chiral helicity in organic molecules relies on a ring extension by means of cycloaddition and related reactions. Recently

• , the peri-functionalization approach paved a new pathway for the generation of chiral helical molecules. In this article, we highlight the key advancements in these parallel approaches for the generation of helical chiral architectures. Keywords: catalysis; C–H functionalization; helical chirality

• another important type of chirality, where the chirality is controlled by restricted rotation among an axis. These types of molecules play an important role as chiral ligands in organic synthesis, i.e., BINOL, BINAP, etc. [9][10][11]. Another form of chirality, where chirality depends on a constrained

Streptoquinolines A and B, new antibacterial meroterpenoids produced by Streptomyces sp. TMPU-A0679

• Akiho Yagi,
• Hitomi Tomura,
• Ami Konno and
• Ryuji Uchida

Beilstein J. Org. Chem. 2026, 22, 185–191, doi:10.3762/bjoc.22.12

• 1H,1H COSY and HMBC correlations as those observed for 1 (Figure 2), confirming that compound 2 shared the same planar structure. The specific rotations of 1 and 2 were similar in both sign and magnitude, suggesting that they shared the same absolute configuration for most chiral centers. However, a

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

• RU58841. Moreover, chiral alcohols such as ʟ-menthol are well tolerated, affording diastereomeric sulfinimidate esters that can undergo stereospecific Grignard substitutions to furnish enantioenriched sulfilimines with up to 93% ee. These results demonstrate the potential of sulfinimidate esters as

• PIDA-mediated oxidative esterification of sulfenamides, rely on stoichiometric hypervalent iodine reagents and have not demonstrated broadly efficient reactivity with sterically demanding or chiral alcohols such as ʟ-menthol, where only modest conversion was observed in our hands. Motivated by these

• , we anticipated that an NBS/NaHCO3-based protocol would provide a more practical and chiral-alcohol-compatible alternative to our previous PIDA system. A conceptual comparison between our previous PIDA-mediated protocol and the present NBS/NaHCO3-mediated protocol is summarized in Scheme 1. However

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

• compounds, and catalyst J as a trifluoroacetylated chiral tertiary amine, which lacks iodine. The reaction of imine 1 with dimethyl malonate was selected for the investigation as a model reaction. Based on our previous experience the catalyst screening was carried out in toluene in the presence of 10 mol

• ]. Although basic conditions caused partial racemization during the protection or deprotection step, the Boc-protected amine was obtained in low enantiomeric purity. Chiral HPLC analysis and comparison with an authentic sample revealed the S-configuration of the Mannich adduct [29]. Absolute configurations of

• . Although the activation mechanism was not proved unambiguously, it is assumed that steric effects of the chiral fragment together with a network of noncovalent interactions, including halogen and hydrogen bonds, are responsible for the high enantioselectivity of the reaction. Further developments of the

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• chiral platinum(II) complex was synthesized via Sonogashira coupling and subsequent coordination of a pincer ligand to a precursor. The complex exhibited a broad absorption band ranging from 250 to 550 nm in the UV–vis spectrum, with TD-DFT calculations indicating mixed ligand-to-ligand charge transfer

• increased to 4%. CD spectra showed distinct Cotton effects in the MLCT region, and CPL signals were observed only in the PMMA matrices, with a dissymmetry factor |glum| = 0.4 × 10−3. These results demonstrate that axial chirality of the binaphthyl moiety governs the three-dimensional chiral arrangement of

• two platinum(II) chromophore units, leading to the chiroptical properties in the MLCT region through exciton coupling under restricted molecular motion. Keywords: axial chirality; chiral chemistry; circularly polarized luminescence (CPL); phosphorescence; platinum(II) complex; Introduction

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• obtained as a racemic diastereomeric pair 1SR,2RS. Centrosymmetric crystals 9a and 9b are diastereomers and crystallize as a true racemate. The configuration of the chiral atoms C1 and C2 in the molecules is the same as in molecules 2, and the difference is the configuration of atom C3. In crystal 9a, 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

• in the presence of metal catalysts including Pd or Ir and different ligands. In 2021 and 2022, Wang and co-workers reported two impressive hydroboration–hydrogenation reactions catalyzed by FLP (triarylphenylborane) that reduced pyridine compounds 11 or 15 to dihydropyridine compounds 12 or chiral

• 18, 20 to piperidine compounds using [CpRhCl2]2 as a metal catalyst and formic acid as a hydrogen source (Scheme 3) [45]. Different with other previous studies, this method allows for substituents at the 3-position of pyridine, enabling the rapid preparation of chiral piperidine compounds. It should

• limitations in terms of substrate scope, stereoselectivity, and scalability, leaving ample room for innovation in catalyst design and mechanistic understanding. Fan and co-workers have long been dedicated to the asymmetric catalysis of chiral diamine ruthenium complexes. In 2020, they reported the efficient

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

• issue, the authors first examined a model system. When β-alkoxythioesters (S)-52 were coupled with chiral alkyl iodides (S)-53 and (R)-53 under the developed conditions, the desired β-alkoxy ketones 54 were obtained in good yields without epimerization, affording optically pure products. These results

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

• , catalyzed by a chiral copper complex generated in situ from CuTC and phosphoramidite ligand 361, furnished the corresponding enantioenriched alkenyl chlorides in high yield and with exclusive formation of the Z-isomer. A decade later, Fañanás-Mastral and co-workers demonstrated that alkenylcopper species

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

• starting chiral synthon (chiron), and to regioselectively install a prenyl group at different sites on the indole moiety (Figure 2, approach A, A–C) [23][24]. This would formally mimic the post-translational biosynthetic pathway wherein a prenyl group would be inserted at C4–C7 selectively via the prenyl

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

• methyl ketones increases the regioselectivity in the synthesis of octahydropyrido[1,2-a]pyrimidinones. The cyclization with acetophenone is characterized by the regiospecific generation of these bicycles. The presence of three chiral centers in the synthesized bicycles, depending on the alkyl substituent

• increase in the regioselectivity of octahydropyrido[1,2-a]pyrimidinones formation. In contrast, the cyclization with acetophenone occurs regiospecifically, yielding only octahydropyrido[1,2-a]pyrimidinones. The presence of three chiral centers in the synthesized bicycles leads to the formation of

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

• 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

• Seyferth–Gilbert homologation with the Ohira–Bestmann reagent to conclude the synthesis of piperidine fragment 116 constituting the later F-ring. The two chiral fragments were conjoined by alkylation of piperidinone 116 with propargyl bromide 112 to provide triyne

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

• ][2][3][4][5][6]. Recently developed photocatalysis affords sustainable, regioselective green methods for producing a wide range of functionalized carbonyl compounds and their related bioactive chiral intermediates under mild conditions, employing dual organic photoredox catalysis [7][8][9][10][11

• transformations. Previous reports displayed various research groups successfully designed and prepared a variety of triazolium-based NHCs, eventually leading to the development of chiral NHC scaffolds by Knight and Leeper [17], followed by the remarkable contributions of Bode [18], Rovis [19], Glorius [20

• , 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

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

• series of structurally simple and readily accessible precursor compounds [2]. Based on this philosophy, chemists have developed a variety of classical synthetic strategies to address target molecules with diverse structural features. For instance, “divergent synthesis” employs a universal chiral advanced

• of the non-naturally produced ryanodol (4) and its dehydrated derivative, anhydroryanodol (10) [30] (Scheme 2). Given the highly complex fused-ring system and the stereochemical challenges posed by multiple chiral centers, the author utilized the Diels–Alder reaction, a prominent representative of

• pericyclic reactions [31][32][33][34][35][36][37][38][39][40][41][42][43][44], to control the formation of the crucial C5 chiral center precisely. Subsequent oxidative cleavage of the carbon–carbon double bond introduced in the Diels–Alder reaction, followed by an intramolecular aldol reaction, efficiently

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• Abstract The total synthesis of bioactive (+)-aglacin B was achieved. The key steps include an asymmetric conjugate addition reaction induced by a chiral auxiliary and a nickel-promoted reductive tandem cyclization of the elaborated β-bromo acetal, which led to the efficient construction of the

• diastereocontrol for 12 (dr = 20:1), and could easily proceed on a scale of ten grams (Supporting Information File 1). For the reduction of the chiral auxiliary in 12, NaBH4 in THF/H2O proved to be the optimal conditions, giving the primary alcohol 6 in 80% yield. Subsequently, oxidation of this alcohol by IBX

• single crystals, and a corresponding X-ray diffraction analysis (inset in Scheme 3, selected H atoms have been omitted for clarity, and Table S3, Supporting Information File 1) unambiguously confirmed its precise structure with three continuous chiral centers. Conclusion In summary, the total synthesis

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

• Qi-Sen Gao Zheng-Wei Wei Zhi-Min Chen State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai 200240, P. R. China 10.3762/bjoc.21.186 Abstract

• . Keywords: asymmetric catalysis; atropisomer; chiral selenium-containing compound; C–Se bond formation; Introduction Selenium is an essential trace element for human body [1]. It plays an important role in metabolism. In 1817, the Swedish chemist Berzelius found that red residual mud was attached to the

• many applications in industry, but also plays an important role in many fields, such as electronics [3], agriculture [4], environmental protection [5] and cosmetics [6]. Chiral organic selenium-containing compounds also have important applications in organic synthesis and biomedicine [7][8]. These

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

• -dihydronaphthalenes. Silva et al. have also developed an effective method for the stereoselective oxidation of tetralone derivatives using chiral hypervalent iodine reagents [61][62]. Hypervalent iodine compounds are widely used in organic synthesis as selective oxidants and enantiomerically pure reagents. In terms

• 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

• challenging [6-5-5-7]-tetracyclic ring system embedded within a fully functionalized cyclopentane, as well as seven contiguous stereogenic centers. In 2017, (−)-pavidolide B (134) was prepared in 13 steps from the known chiral alcohol 135, which in turn was synthesized from commercially available (+)-carvone

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• yield substituted spiropyrrolidines (Scheme 1, path b) [9]. Additionally, an organocatalytic, enantioselective Michael addition/cyclization sequence of 3-aminooxindole Schiff bases with terminal vinyl ketones, catalyzed by a cinchona-derived base, has been reported to afford chiral spiroindolylpyrroles

• under heating furnished chiral spiroindolylpyrroles in excellent yields and enantioselectivity (Scheme 1, path d) [11]. Moreover, a copper-catalyzed reaction of oxindole-derived alkenes with acetophenone O-acetyl oxime has also been employed to construct the spiroindolylpyrrole scaffold (Scheme 1, path

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• selective recognition. Balancing binding affinity and selectivity through precise conformational engineering remains a critical challenge [11]. Previous studies, such as those by Tian et al. [12], demonstrated selective binding in chiral assemblies via crown ether chain-length modulation. The dynamic

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

• biomembrane-compatible rotaxanes are promising for designing artificial ion transporters to address channelopathies. Song and co-workers developed a system in which the azobenzene in the axle is encapsulated within a chiral β-cyclodextrin, affording a self-locked [1]rotaxane [15]. The intramolecular host

• –guest interaction induces a chiral signal, while the azobenzene chromophore imparts photoswitching properties to the molecule. Furthermore, solvent-mediated hydrogen-bonding interactions tailored within the inner cyclodextrin cavity, combined with photocontrolled isomerization of the azo moiety, enable

• dual orthogonal manipulation of the rotaxane’s conformational regulation and chiroptical switching properties. Thus, this system functions as a phototriggered chiral on–off switch in polar aprotic solvents. These types of rotaxanes hold promise for developing simple information storage materials and

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

• approaches. Overall, their synthesis highlights the impact of enabling transition metal catalysis on natural product total synthesis. The Siegel synthesis starts with chiral pool molecule (+)-pulegone (14), which encodes the first stereocenter of the entire sequence. (+)-Pulegone was converted to compound 15

• with MeI in presence of benzyltrimethylammonium fluoride (BTAF). At this stage, to prepare optically active natural product, the racemic mixture of 51 was separated using chiral HPLC to afford (+)-51 and (−)-51, which were used to prepare both enantiomers of complanadine A for biological evaluations

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

• -diketones, the rigid lattice structure locks molecules into a specific conformation, limiting access to certain γ-hydrogens for abstraction and thus enhancing regioselectivity [42]. Enantiopure 87 was obtained by preparative chiral supercritical fluid chromatography (SFC) resolution of the racemate, while

• epimers. This strategy merges photochemical selectivity with cross-coupling efficiency, avoiding reactive metal incompatibility and enabling precise stereocontrol for chiral nitrogen heterocycles. 3 Antibiotics 3.1 Synthetic study toward γ-rubromycin Since 2017, Suzuki's group has developed a

• inhibitor [53][54]. In 2018, Suzuki’s group employed their developed photoredox reaction to carry out a model study on the chiral [5,6]-spiroketal core of γ-rubromycin [50]. 1,2-Naphthoquinone 106 was selected as the model substrate for the photoredox reaction (Scheme 13a). Lawsone (101) underwent reductive

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

• previously for an anthracene-walled glycoluril tetramer host [43], G2W3 undergoes an end-to-end twist due to splaying of the aromatic sidewalls that results in an overall helical conformation that is chiral. The angle between the mean planes of the naphthalene rings amounts to 42.490°. Most relevant to the

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

• [14][15]. In recent years, the chiral biomass derivatives levoglucosenone (LGO, 5) and its reduced form Cyrene® (6) have gained increased attention as platforms for drug discovery [16][17][18][19]. The bicyclic ketone 5 is the major product from the pyrolysis of acid-treated cellulose [20], while its

• ready availability of enamine 9a; however, direct double halogenation of 6 may also be possible using an excess of halogenation agent in DMSO [31]. The Baeyer–Villiger oxidation using H2O2 in MeCN gave the desired chiral lactones 11a and 11b in moderate to good yield following an acidic workup to cleave

• chiral halogenated lactones, which could be useful in the enantioselective synthesis of valuable drug precursors. The syntheses feature the use of readily available and cheap starting materials, and we have also demonstrated some of these transformations on a gram scale. Halogen-containing butyrolactone