Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• , pharmaceutical compounds, and chiral ligands. The Lewis acid-catalyzed ring-opening reaction of cyclohexene oxide by MeZH (Z = O, S, and NH) is well known [20]. However, studies on large-sized bicyclic epoxides remain relatively limited in the published literature. In our previous study, we performed the ring

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

• , Nicolaou and co-workers merged both building blocks within a Ni(II)/Cr(II)-catalyzed NHK reaction using chiral ligand 206 (Scheme 23) [95]. Upon treatment with DBU, 3-methylenetetrahydrofuran 201 was obtained in 56% yield over two steps. PMB-deprotection, iodination and selective reduction of the ester

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

• distal axial chiralities are widely applied in chiral ligands, natural products, and anticancer agents, with their unique spatial configurations endowing them with distinctive functions and values. Although significant progress has been made in the asymmetric synthesis of distal biaxial chirality

• biaxial chirality, multistep sequential generation, and conversion from central to biaxial chirality, with the aim of providing new perspectives and methodologies for further development in this area. Keywords: axially chiral compounds; stereoselective synthesis; Introduction In recent years, axially

• chiral scaffolds, which arise from hindered rotation between two planes connected by a single bond, have attracted increasing attention due to their widespread applications in chiral ligands, organocatalysts [1], and functional materials [2], making them highly valuable molecular frameworks in organic

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

• Pharmacy, Shenzhen Technology University, Shenzhen 518118, China 10.3762/bjoc.22.31 Abstract The synthesis of racemic trans-taxifolin (trans-(±)-taxifolin) and its derivatives and subsequent chiral separation is the most prevalent chemical method to obtain enantiomerically pure taxifolin and its

• transformation from dietary food to multifunctional medications in the near future. Taxifolin is a chiral compound with two stereocenters and exists as trans or cis isomers. It is commonly referred to as the trans dextral form (trans-(+)-taxifolin), which has higher bioactivity than its levorotatory enantiomer

• produce taxifolin but also faces the problems of scale-up and high cost. As a result, the development of a practical synthetic approach is of importance and significance. A chiral synthesis for taxifolin was reported by the use of (+)-catechin as the starting material [15][16], but (+)-catechin is not

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• Advanced Science and Technology, Kumamoto University, Kurokami, Kumamoto 865-8555, Japan 10.3762/bjoc.22.30 Abstract Planar chiral C6-substituted oxa[7]orthocyclophenes were designed and synthesized, and their stereochemical behavior was analyzed. The Kumada–Tamao coupling of the C6-iodo-substituted

• successfully transformed into central chirality by epoxidation without loss of enantiomeric purity. Keywords: dynamic chirality; medium-sized heterocycle; orthocyclophene; planar chirality; stereochemical analysis; Introduction In the course of our study on planar chiral medium-sized cyclic molecules [1][2

• ideal alkene plane. Stereochemical analysis of C6-substituted oxacyclophenes Next, HPLC analyses using a chiral stationary phase (chiral column) of the C6-substituted oxacyclophenes were conducted. The baseline separations of the enantiomers of 1ab and 1ad were achieved by using CHIRALCEL OJ-H as the

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• corresponded to chiral C2-symmetric homodimeric capsules in both cases. The 1H NMR spectrum of the equimolar mixture 48/52 (taken as an example) contained one set of signals from the C2-symmetric heterodimer 48·CDCl3·52, but not from the homodimers 48·CDCl3·48 and 52·CDCl3·52, and thus reflected the expected

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• Heterohelicenes are compelling chiral π-conjugated scaffolds for optoelectronic and chiral-photonic technologies because their helical frameworks and doped heteroatoms endow them with various photophysical, chiroptical, and electronic merits. However, unsymmetrical heterohelicenes remain rare, as their synthesis

• ) relative to their oxaza[7]helicene analogues (<25 kcal/mol). After chiral HPLC separation, the enantiomers display mirror-image CD and strong solution CPL, with |glum| up to 2.6 × 10−3 and fluorescence brightness up to 30.75 M−1 cm−1. Keywords: chemoselectivity; chiroptical; circular dichroism

• ; electrochemistry; emission; helical elongation; helicene; photophysical; Introduction Chirality is a pervasive feature of natural and artificial systems, and chiral small molecules continue to underpin advances in chemistry and materials science [1][2]. Among them, helicenes – ortho-condensed polycyclic aromatic

Non-central chirality in organic chemistry

• Ken Tanaka and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2026, 22, 370–371, doi:10.3762/bjoc.22.24

• axial, planar, or helical chirality individually, often organized along specific molecular classes or application-driven themes such as asymmetric catalysis or chiral materials. In contrast, this Thematic Issue deliberately brings together diverse manifestations of non-central chirality under a single

• complementary roles played by non-central chiral molecules in contemporary organic chemistry. First, they continue to serve as demanding benchmarks for asymmetric synthesis, probing how far stereochemical information can be transmitted and controlled when the stereogenic element is spatially or conceptually

• remote from the reaction site. Second, non-central chiral frameworks remain fertile ground for catalyst design, not only as derivatives of established motifs but also as newly conceived architectures that redefine how chirality can be embedded into catalytic systems. Third, the pronounced chiroptical and

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

• undergoes hydrolysis to afford the benzyl ester 30. Under the optimized conditions, primary, secondary, and tertiary amides 12, 31–33 were successfully converted to benzyl esters in high yields. Notably, loss of enantiopurity of chiral amide 33 was not observed during esterification. Sulfuryl fluoride

• electrophilic activation of pyrrolidine-derived amides with Tf2O and 2-bromopyridine generates a keteniminium ion O, which undergoes nucleophilic addition to form an enamine intermediate P. Subsequent electrophilic α-fluorination followed by hydrolysis produces the α-fluoroester products. Notably, the C2-chiral

• amide 44, incorporating (2S,5S)-2,5-diphenylpyrrolidine as a chiral auxiliary, furnished the enantioenriched ester 45* in 64% yield with 90% ee. Wan et al. investigated the chlorination of primary amides using trichloroisocyanuric acid (TCCA) to promote esterification (Scheme 10) [58]. In the presence

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• aromatic ligand is necessary to set the absolute stereochemistry of the organic product. This relative stereochemistry depends on which face of the arene is coordinated and can be governed by high chiral recognition for binding (coordination diastereomer ratio, cdr) or stereoelectronic differentiation

• manifolds) and unlocking enantioselective variants to access three-dimensional, chiral architectures. In contrast, η2- and η4-coordination modes have been explored extensively from a structural and stoichiometric reactivity standpoint, yet catalytic manifestations remain conspicuously rare. The energetic

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