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
Graphical Abstract
Figure 1: Representative alkenyl chloride motifs in natural products. References: Pinnaic acid [8], haterumalide ...
Figure 2: Representative alkenyl chloride motifs in pharmaceuticals and pesticides. References: clomifene [25], e...
Figure 3: Graphical overview of previously published reviews addressing the synthesis of alkenyl chlorides.
Figure 4: Classification of synthetic approaches to alkenyl chlorides.
Scheme 1: Early works by Friedel, Henry, and Favorsky.
Scheme 2: Product distribution obtained by H NMR integration of crude compound as observed by Kagan and co-wo...
Scheme 3: Side reactions observed for the reaction of 14 with PCl5.
Scheme 4: Only compounds 15 and 18 were observed in the presence of Hünig’s base.
Scheme 5: Efficient synthesis of dichloride 15 at low temperatures.
Scheme 6: Various syntheses of alkenyl chlorides on larger scale.
Scheme 7: Scope of the reaction of ketones with PCl5 in boiling cyclohexane.
Scheme 8: Side reactions occur when using excess amounts of PCl5.
Scheme 9: Formation of versatile β-chlorovinyl ketones.
Scheme 10: Mixture of PCl5 and PCl3 used for the synthesis of 49.
Scheme 11: Catechol–PCl3 reagents for the synthesis of alkenyl chlorides.
Scheme 12: (PhO)3P–halogen-based reagents for the synthesis of alkenyl halides.
Scheme 13: Preparation of alkenyl chlorides from alkenyl phosphates.
Scheme 14: Preparation of alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.
Scheme 15: Preparation of electron-rich alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.
Scheme 16: Cu-promoted synthesis of alkenyl chlorides from ketones and POCl3.
Figure 5: GC yield of 9 depending on time and reaction temperature.
Figure 6: Broken reaction flask after attempts to clean the polymerized residue.
Figure 7: GC yield of 9 depending on the amount of CuCl and time.
Scheme 17: Treatment of 4-chromanones with PCl3.
Scheme 18: Synthesis of alkenyl chlorides from the reaction of ketones with acyl chlorides.
Scheme 19: ZnCl2-promoted alkenyl chloride synthesis.
Scheme 20: Regeneration of acid chlorides by triphosgene.
Scheme 21: Alkenyl chlorides from ketones and triphosgene.
Scheme 22: Various substitution reactions.
Scheme 23: Vinylic Finkelstein reactions reported by Evano and co-workers.
Scheme 24: Challenge of selective monohydrochlorination of alkynes.
Scheme 25: Sterically encumbered internal alkynes furnish the hydrochlorination products in high yield.
Scheme 26: Recent work by Kropp with HCl absorbed on alumina.
Scheme 27: High selectivities for monhydrochlorination with nitromethane/acetic acid as solvent.
Figure 8: Functionalized alkynes which typically afford the monhydrochlorinated products.
Scheme 28: Related chorosulfonylation and chloroamination reactions.
Scheme 29: Reaction of organometallic reagents with chlorine electrophiles.
Scheme 30: Elimination reactions of dichlorides to furnish alkenyl chlorides.
Scheme 31: Elimination reactions of allyl chloride 182 to furnish alkenyl chloride 183.
Scheme 32: Detailed studies by Schlosser on the elimination of dichloro compounds.
Scheme 33: Stereoselective variation caused by change of solvent.
Scheme 34: Elimination of gem-dichloride 189 to afford alkene 190.
Scheme 35: Oxidation of enones to dichlorides and in situ elimination thereof.
Scheme 36: Oxidation of allylic alcohols to dichlorides and in situ elimination thereof.
Scheme 37: Chlorination of styrenes with SOCl2 and elimination thereof.
Scheme 38: Chlorination of styrenes with SOCl2 and elimination thereof.
Scheme 39: Fluorine–chlorine exchange followed by elimination.
Scheme 40: Intercepting cations with alkynes and trapping of the alkenyl cation intermediate with chloride.
Scheme 41: Investigations by Mayr and co-workers.
Scheme 42: In situ activation of benzyl alcohol 230 with BCl3.
Scheme 43: In situ activation of benzylic alcohols with TiCl4.
Scheme 44: In situ activation of benzylic alcohols with FeCl3.
Scheme 45: In situ activation of benzylic alcohols with FeCl3.
Scheme 46: In situ activation of aliphatic chlorides and alcohols with ZnCl2, InCl3, and FeCl3.
Scheme 47: In situ generation of benzylic cations and trapping thereof with alkynes.
Scheme 48: Intramolecular trapping reactions affording alkenyl halides.
Scheme 49: Intramolecular trapping reactions affording alkenyl chlorides.
Scheme 50: Intramolecular trapping reactions of oxonium and iminium ions affording alkenyl chlorides.
Scheme 51: Palladium and nickel-catalyzed coupling reactions to afford alkenyl chlorides.
Scheme 52: Rhodium-catalyzed couplings of 1,2-trans-dichloroethene with arylboronic esters.
Scheme 53: First report on monoselective coupling reactions for 1,1-dichloroalkenes.
Scheme 54: Negishi’s and Barluenga’s contributions.
Scheme 55: First mechanistic investigation by Johnson and co-workers.
Scheme 56: First successful cross-metathesis with choroalkene 260.
Scheme 57: Subsequent studies by Johnson.
Scheme 58: Hoveyda and Schrock’s work on stereoretentive cross-metathesis with molybdenum-based catalysts.
Scheme 59: Related work with (Z)-dichloroethene.
Scheme 60: Further ligand refinement and traceless protection of functional groups with HBpin.
Scheme 61: Alkenyl chloride synthesis by Wittig reaction.
Scheme 62: Alkenyl chloride synthesis by Julia olefination.
Scheme 63: Alkenyl chloride synthesis by reaction of ketones with Mg/TiCl4 mixture.
Scheme 64: Frequently used allylic substitution reactions which lead to alkenyl chlorides.
Scheme 65: Enantioselective allylic substitutions.
Scheme 66: Synthesis of alkenyl chlorides bearing an electron-withdrawing group.
Scheme 67: Synthesis of α-nitroalkenyl chlorides from aldehydes.
Scheme 68: Synthesis of alkenyl chlorides via elimination of an in situ generated geminal dihalide.
Scheme 69: Carbenoid approach reported by Pace.
Scheme 70: Carbenoid approach reported by Pace.
Scheme 71: Ring opening of cyclopropenes in the presence of MgCl2.
Scheme 72: Electrophilic chlorination of alkenyl MIDA boronates to Z- or E-alkenyl chlorides.
Scheme 73: Hydroalumination and hydroboration of alkynyl chlorides.
Scheme 74: Carbolithiation of chloroalkynes.
Scheme 75: Chlorination of enamine 420.
Scheme 76: Alkyne synthesis by elimination of alkenyl chlorides.
Scheme 77: Reductive lithiation of akenyl chlorides.
Scheme 78: Reactions of alkenyl chlorides with organolithium reagents.
Scheme 79: Reactions of alkenyl chlorides with organolithium reagents.
Scheme 80: Addition–elimination reaction of alkenyl chloride 9 with organolithium reagents.
Scheme 81: C–H insertions of lithiumcarbenoids.
Scheme 82: Pd-catalyzed coupling reactions with alkenyl chlorides as coupling partner.
Scheme 83: Ni-catalyzed coupling of alkenylcopper reagent with alkenyl chloride 183.
Scheme 84: Ni-catalyzed coupling of heterocycle 472 with alkenyl chloride 473.
Scheme 85: Synthesis of α-chloroketones by oxidation of alkenyl chlorides.
Scheme 86: Tetrahalogenoferrate(III)-promoted oxidation of alkenyl chlorides.
Scheme 87: Chlorine–deuterium exchange promoted by a palladium catalyst.
Scheme 88: Reaction of alkenyl chlorides with thiols in the presence of AIBN (azobisisobutyronitrile).
Scheme 89: Chloroalkene annulation.
Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene
- Dmitry N. Platonov,
- Alexander Yu. Belyy,
- Rinat F. Salikov,
- Kirill S. Erokhin and
- Yury V. Tomilov
Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2
Graphical Abstract
Figure 1: The expected and the unexpected in selected synthetic strategies.
Figure 2: Distortion in antiaromatic hepta- and hexa(methoxycarbonyl)cycloheptatrienyl anions 1 and 2. HOMO (...
Scheme 1: Reactions of anion 2 generated from cycloheptatriene 3 with halogens and alkyl halides.
Scheme 2: Reactions of anion 2 generated from cycloheptatriene 3 with diazonium salts.
Figure 3: Two conformers of hexa(methoxycarbonyl)cycloheptatrienyl anion 2 and 2'. The energies were obtained...
Scheme 3: Radical mechanism for reactions of anion 2 with halogens, suggested structure of trapped product. T...
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
Graphical Abstract
Figure 1: Historical background of zirconium and its physical properties. Image depicted in the background of ...
Scheme 1: Zr-mediated radical cyclization.
Scheme 2: Ni/Zr-mediated one-pot ketone synthesis.
Scheme 3: Zirconocene-catalyzed alkylative dimerization of 2-methylene-1,3-dithiane.
Scheme 4: Zirconium complexes as a photoredox catalyst.
Scheme 5: Zr-catalyzed reductive ring opening of epoxides.
Scheme 6: Zr-catalyzed reductive ring opening of oxetanes. a10 mol % of Cp2Zr(OTf)2·THF was used. bPhCF3 was ...
Scheme 7: Zr-catalyzed halogen atom transfer of alkyl chlorides.
Scheme 8: Zr-catalyzed radical homo coupling of alkyl chlorides.
Scheme 9: Zr-catalyzed fluorine atom transfer.
Scheme 10: Zr-catalyzed C–O bond cleavage. aYield without the use of P(OEt)3.
Scheme 11: Application to the total synthesis of halichondrins.
Scheme 12: Zr-catalyzed C3 dimerization of 3-bromotryptophan derivatives. aCp2ZrCl2 was used.
Scheme 13: Mechanistic studies.
Scheme 14: Application to the total synthesis of cyctetryptomycins. A photo of compound 61b was taken by the a...
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
Graphical Abstract
Scheme 1: The association between dearomatization and natural product synthesis.
Scheme 2: Key challenges in hydrogenation of aromatic rings.
Scheme 3: Hydrogenation of heterocyclic aromatic rings.
Scheme 4: Hydrogenation of the carbocyclic aromatic rings.
Scheme 5: Hydrogenation of the heterocycle part in bicyclic aromatic rings.
Scheme 6: Hydrogenation of the heterocycle part in bicyclic aromatic rings.
Scheme 7: Hydrogenation of benzofuran, indole, and their analogues.
Scheme 8: Hydrogenation of benzofuran, indole, and their analogues.
Scheme 9: Total synthesis of (±)-keramaphidin B by Baldwin and co-workers.
Scheme 10: Total synthesis of (±)-LSD by Vollhardt and co-workers.
Scheme 11: Total synthesis of (±)-dihydrolysergic acid by Boger and co-workers.
Scheme 12: Total synthesis of (±)-lysergic acid by Smith and co-workers.
Scheme 13: Hydrogenation of (−)-tabersonine to (−)-decahydrotabersonine by Catherine Dacquet and co-workers.
Scheme 14: Total synthesis of (±)-nominine by Natsume and co-workers.
Scheme 15: Total synthesis of (+)-nominine by Gin and co-workers.
Scheme 16: Total synthesis of (±)-lemonomycinone and (±)-renieramycin by Magnus.
Scheme 17: Total synthesis of GB13 by Sarpong and co-workers.
Scheme 18: Total synthesis of GB13 by Shenvi and co-workers.
Scheme 19: Total synthesis of (±)-corynoxine and (±)-corynoxine B by Xia and co-workers.
Scheme 20: Total synthesis of (+)-serratezomine E and the putative structure of huperzine N by Bonjoch and co-...
Scheme 21: Total synthesis of (±)-serralongamine A and the revised structure of huperzine N and N-epi-huperzin...
Scheme 22: Early attempts to indenopiperidine core.
Scheme 23: Homogeneous hydrogenation and completion of the synthesis.
Scheme 24: Total synthesis of jorunnamycin A and jorumycin by Stoltz and co-workers.
Scheme 25: Early attempt towards (−)-finerenone by Aggarwal and co-workers.
Scheme 26: Enantioselective synthesis towards (−)-finerenone.
Scheme 27: Total synthesis of (+)-N-methylaspidospermidine by Smith, Grigolo and co-workers.
Scheme 28: Dearomatization approach towards matrine-type alkaloids.
Scheme 29: Asymmetric total synthesis to (−)-senepodine F via an asymmetric hydrogenation of pyridine.
Scheme 30: Selective hydrogenation of indole derivatives and application.
Scheme 31: Synthetic approaches to the oxindole alkaloids by Qi and co-workers.
Scheme 32: Total synthesis of annotinolide B by Smith and co-workers.
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
Graphical Abstract
Figure 1: Two natural trichloromethyl-containing compounds.
Scheme 1: Approaches to the synthesis of vic-trifluoromethylnitrocyclopropanes.
Scheme 2: Synthesis of monocyclic trichloromethylnitrocyclopropanes 2–5.
Scheme 3: Synthesis of spiro-fused trichloromethylnitrocyclopropane 6.
Scheme 4: Synthesis of spiro-fused trichloromethylnitrocyclopropanes 7–9. i: 1.5 AcOK, MeOH, rt, 3 h.
Scheme 5: Main NOE correlations in 9a, 9b.
Scheme 6: Proposed mechanism of the formation of trichloromethylnitrocyclopropanes.
Figure 2: Geometry of 2 in the crystal.
Figure 3: Geometry of 3 in the crystal.
Figure 4: Geometry of 9a in the crystal.
Figure 5: Geometry of 9b in the crystal.
Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection
- Ergin Keleş,
- Alberto Barsella,
- Nurgül Seferoğlu,
- Zeynel Seferoğlu and
- Burcu Aydıner
Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6
Graphical Abstract
Figure 1: Design of the functional dyes.
Scheme 1: Synthetic pathway of compounds.
Figure 2: Normalized absorption spectra of dyes 2a (a), 2b (b), and 2c (c); Photographs of dyes in the given ...
Figure 3: Absorption spectra of dyes 2a (a), 2b (b), and 2c (c) upon addition of 20 equiv of anions in DMSO; ...
Figure 4: Absorption spectra of titrated dyes (2a–c) with up to 50 equiv of CN− (a) 6:4, (b) 7:3, and (c) 4:6...
Figure 5: Partial 1H NMR spectral change of 2b (c = 10 mM) after up to 2 equiv of TBACN (c = 1 M) in DMSO-d6.
Scheme 2: Proposed interaction mechanism with CN−.
Figure 6: Optimized geometries of 2a–c and 2a–c+CN− obtained at the B3LYP/6-31+G(d,p) level.
Figure 7: Frontier molecular orbitals of a) 2a, b) 2a+CN−.
Figure 8: TGA curves of dyes.
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
Graphical Abstract
Figure 1: Molecular design for axially chiral platinum(II) complex S/R-Pt based on a pincer ligand.
Scheme 1: Synthesis of the binaphthyl-based ligand and the platinum(II) complex. Yields indicated correspond ...
Figure 2: (a) UV–vis and PL spectra (λex = 300 nm) in 1.0 × 10−5 M dichloromethane solution, the gray dotted ...
Figure 3: Emission spectrum of 1 wt % PMMA matrix (R-Pt) (λex = 300 nm).
Figure 4: (a) CD spectra of S/R-Pt in 1.0 × 10−5 M dichloromethane solution. (b) CPL spectra of 1 wt % PMMA f...
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
Graphical Abstract
Scheme 1: The catalytic Mannich reaction under study.
Figure 1: Screened catalysts.
Figure 2: Model for the interaction of the catalyst with the imine.
Figure 3: Substrate scope of the asymmetric Mannich reaction.
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
Graphical Abstract
Figure 1: Representative molecules containing a sulfilimine moiety.
Scheme 1: PIDA-mediated approach versus the present NBS-mediated approach to sulfinimidate esters.
Scheme 2: Substrate scope of sulfenamides derived from various thiophenols and thiols. Reaction conditions: s...
Scheme 3: Substrate scope of sulfenamides derived from various amides. Reaction conditions: sulfenamide 1 (0....
Scheme 4: Substrate scope of reactions between sulfenamides 1a and various alcohols. Reaction conditions: asu...
Scheme 5: Scale-up synthesis, late-stage derivatization, and substitution of diastereomeric sulfinimidate est...
A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts
- Holly Helmers,
- Mark Horton,
- Julie Concepcion,
- Jeffrey Bjorklund and
- Nicholas C. Boaz
Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10
Graphical Abstract
Scheme 1: A) Generalized synthetic scheme for several previous syntheses of 6,6’-dibromoindigo. B) The synthe...
Scheme 2: Synthetic scheme for the preparation of 6,6’-dibromoindigo from p-bromotoluene (5).
Scheme 3: Nitration of p-bromotoluene (5) yields a mixture of regioisomers 3 and 7.
Scheme 4: Benzylic bromination of 4-bromo-2-nitrotoluene (3).
Scheme 5: A) Treatment of 4-bromo-2-nitrobenzyl bromide (6) with DMSO did not yield the alkoxysulfonium ion i...
Scheme 6: Condensation of 4-bromo-2-nitrobenzaldehyde (4) to yield 6,6’-dibromoindigo (1).
Scheme 7: A) Disulfonation of 6,6’-dibromoindigo (1), to yield 6,6’-dibromo-5,5’-indigodisulfonic acid disodi...
Figure 1: A) UV–vis spectra of 6,6’-dibromo-5,5’,7-indigotrisulfonic acid trisodium salt (10) (10 μM) in aque...
Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH
- Adrian G. Rossebø,
- Hannah G. Kolberg,
- Anders E. Tønder,
- Louise Kjaerulff,
- Poul Erik Hansen,
- Karla A. Frydenvang,
- Jesper Østergaard and
- Jesper L. Kristensen
Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11
Graphical Abstract
Figure 1: Synthesis of 25CN-NBOH·HCl (1·HCl). a) 2C-CN is available in 4 steps from 2C-H [12]: 1) TFAA, TEA, DCM;...
Figure 2: a) Single-crystal X-ray structure of 1·HCl. Displacement ellipsoids of the nonhydrogen atoms are sh...
Figure 3: SCXRD and XRPD spectra of different preparations of 1·HCl. Blue: SCXRD spectrum of 1·HCl. Red, gree...
Figure 4: TGA and DSC thermograms of 1·HCl.
Figure 5: Calculated pH-dependent species distribution curves for 25CN-NBOH (1).
Figure 6: a) Structure of the truncated model compound used for DFT calculations, with explicit water molecul...
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
Graphical Abstract
Figure 1: Structures of streptoquinolines A (1) and B (2).
Figure 2: Structural elucidation of compounds 1 and 2 by 2D NMR experiments.
Figure 3: ROESY correlations of 1.
Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation
- Vladimir G. Ilkin,
- Margarita Likhacheva,
- Igor V. Trushkov,
- Tetyana V. Beryozkina,
- Vera S. Berseneva,
- Vladimir T. Abaev,
- Wim Dehaen and
- Vasiliy A. Bakulev
Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13
Graphical Abstract
Scheme 1: Previous reports (A‒C) and our work (D, E).
Scheme 2: Oxidation of 2-acetyldihydrothiophenes 1. Conditions: dihydrothiophenes 1 (0.12–0.21 mmol, 1.0 equi...
Scheme 3: Deacylation of 2-acetyldihydrothiophenes 1. Conditions: dihydrothiophenes 1 (0.11–0.18 mmol, 1.0 eq...
Scheme 4: Synthesis of dihydrothiophenes 5. Conditions: dihydrothiophenes 4 (0.13–0.22 mmol, 1.0 equiv), sodi...
Scheme 5: Control experiments.
Figure 1: HRMS analysis of the crude product.
Figure 2: UV–vis spectra of the crude mixture (5.6 mg of the crude mixture was dissolved in 15 mL of methanol...
Scheme 6: Proposed mechanism.
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
Graphical Abstract
Figure 1: Representation of the general practices for the induction of helical chirality in organic scaffolds...
Scheme 1: Asymmetric synthesis of carbohelicenes via peri-C–H functionalization.
Figure 2: Stereomodel for peri-terminal functionalization of carbohelicene. (Figure 2 was reproduced from [32] (© 2024 X....
Scheme 2: Scale-up synthesis and post-synthetic application of chiral helical product 3.
Scheme 3: Asymmetric peri-C–H functionalization of nitro-substituted oxa[5]helicenes.
Scheme 4: Scale-up synthesis and post-synthetic application of chiral helical product 8g.
Scheme 5: Post-synthetic transformation of product 8g to chiral phosphine ligand 12 and its application in Pd...
Figure 3: Stereomodel for the asymmetric peri-C–H functionalization of oxa[5]helicene. (Figure 3 was reproduced from [33]...
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
Graphical Abstract
Scheme 1: Structure of phytic acid.
Figure 1: Structures of representative phosphate esters.
Figure 2: Synthetic methods for phosphorus compounds bypassing white phosphorus or phosphorus chloride.
Figure 3: Conditions for the syntheses of diaryl phosphates using phytic acid as a phosphorus source and scop...
Scheme 2: Phosphoric acid diesterification reaction conducted in a previous study.
Scheme 3: Scale-up reaction conducted for the time-course analysis of phosphate esterification. The reaction ...
Figure 4: Time-course analysis plots of the diphenylphosphate formation from phytic acid and 1a. The beginnin...
Figure 5: A possible reaction pathway for the formation of phosphate ester using phytic acid as the phosphoru...
Figure 6: 31P NMR spectrum of phytic acid extracted from rice bran.
Scheme 4: Esterification reaction conditions using the extracted phytic acid. The yield refers to the isolate...
Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF
- Ruiyan Wang and
- Yunan Wu
Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16
Graphical Abstract
Figure 1: a) Single-crystal structure of 1, b) HOMO distribution calculated on the crystallographic geometry,...
Figure 2: Photophysical properties of 1 in solvents of varying polarity: a) UV–vis absorption spectra and b) ...
Figure 3: Fluorescence and phosphorescence spectra of 1 in THF (excitation wavelength: 365 nm).
Figure 4: a) Steady-state and delayed emission spectra of 1, b) room-temperature emission lifetimes monitored...
Figure 5: a) Phosphorescence spectra of 1 in the powder state at room temperature and at 77 K, and in dilute ...
Figure 6: a) The bimolecular packing arrangement in the crystal of 1 and intersystem crossing pathways of 1 i...
Figure 7: Photoluminescence lifetime of vacuum-deposited 1 films at different temperatures (excitation wavele...
Figure 8: a) TG curve of 1 and b) DSC curve of 1.
Figure 9: a) Electroluminescence spectrum of the device with 1 as the emissive layer, b) relationship between...
Scheme 1: Synthetic pathway to 1 via imide formation and Suzuki–Miyaura cross-coupling.
Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations
- Matheus P. Freitas
Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17
Graphical Abstract
Figure 1: Structure of racemic difluoromethylornithine (DFMO) and conformers I–III of the (S)-enantiomer ((S)...
Figure 2: Representative conformations of (S)-DFMO with their relative electronic energies (in kcal mol−1), s...
Figure 3: (S)-DFMO bound within the active site of human arginase I obtained from the Protein Data Bank (3GN0...
Figure 4: Lowest-energy type-I, type-II, and type-III conformers of the zwitterionic form of (S)-DFMO. Color ...
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
Graphical Abstract
Figure 1: Examples of biologically active quinolin-2(1H)-ones.
Figure 2: Structures obtained via rational design aimed at enhancing antibacterial activity.
Scheme 1: Previously reported and newly developed 3-(4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-3-arylpropanoi...
Scheme 2: Retrosynthetic analysis: two alternative approaches to target compounds.
Scheme 3: Two-stage synthesis A) and one-stage one-pot synthesis B) of 6-halogen-4-hydroxyquinoline-2(1H)-one...
Scheme 4: Previous synthetic attempts toward the target chemotype using various approaches.
Scheme 5: Four-component synthesis of 3-(6-halo-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-3-(3,4-dimethoxyphe...
Scheme 6: The proposed mechanism of the four-component reaction.
Scheme 7: Synthesis of isopropyl (12a–c) and cyclohexyl (13а–с) esters of 3-(4-hydroxy-2-oxo-1,2-dihydroquino...
Figure 3: In vitro antibacterial activity studies. А) In vitro antibacterial activity using the E. coli ΔtolC...
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
Graphical Abstract
Figure 1: Aromatic molecules as the foundation of modern molecular chemistry.
Figure 2: Arenes as springboards to three-dimensional chemical space and strategies toward arene activation v...
Figure 3: Structure and synthetic utilization of strained arenes; NICS: nucleus independent chemical shifts [26-28].
Figure 4: Bonding and reactivity of η2-coordinated aromatic systems [44,46].
Figure 5: Illustrative selection of η2-coordinating dearomatization agents; MeIm: N-methylimidazole, NHE: nor...
Figure 6: Preparation, lability and most stable linkage isomers of pentaammineosmium(II) complexes.
Scheme 1: Heteroatom-directed reactions of η2-arene complexes [45,50].
Figure 7: Latent functionality through transient metal binding.
Figure 8: Selective hydrogenation of η2-coordinated benzene to cyclohexene under ambient conditions [53,54].
Scheme 2: Synthesis and utilization of enantioenrichted Mo(η2-arene) complexes in enantioselective synthesis [55]....
Scheme 3: Synthesis of trisubstituted cyclohexenes from phenyl sulfones enabled by tungsten-mediated dearomat...
Scheme 4: Diels–Alder reactions of η2-arene complexes with alkenes and alkynes; NMM: N-methylmaleimide [64,65].
Scheme 5: Binding characteristics and pioneering examples of isolable η3-benzyl complexes.
Figure 9: Divergent functionalization of benzyl electrophiles leveraging η3-benzyl complexes toward benzylic ...
Scheme 6: p-Selective allylation of benzyl chlorides with allylstannanes and subsequent synthetic expansion o...
Figure 10: Strategies for para- and ortho-selective arene functionalization/dearomatization via η3-benzyl comp...
Scheme 7: Substrate-dependent ortho- and para-selective dearomatization of naphthyl chlorides and leveraging ...
Figure 11: η4-Arene coordination as an underexplored but promising pathway for arene activation [96,98-100].
Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation
- Arthur A. Puzyrkov,
- Andrew S. Drachuk,
- Ekaterina A. Popova,
- Alexander V. Stepakov and
- Vitali M. Boitsov
Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20
Graphical Abstract
Scheme 1: Biologically active compounds with a spirobarbiturate moiety in their structure [7-12].
Scheme 2: Biologically active alkaloids with a pyrrolizidine moiety.
Scheme 3: Previous studies on the three-component synthesis of spirobarbiturates.
Scheme 4: Synthesis of racemic spirobarbiturates 4a–p via one-pot three-component reaction of alloxan (1), ʟ-...
Scheme 5: A plausible mechanism of spirobarbiturate formation from alloxan (1), ʟ-proline (2), and N-substitu...
Figure 1: Schematic structures of endo- and exo-adducts of spirobarbiturates 4.
Figure 2: X-ray crystal structures of compounds 4b (CCDC 2391172, left) and 4c (CCDC 2391171, right).
Figure 3: Unit cell packing of products 4b (left) and 4c (right).
Figure 4: HS mapped with dnorm for compounds 4b (left) and 4c (right).
Figure 5: A segment of the crystal structure of compound 4b with the HS (dnorm), showing intermolecular conta...
Figure 6: A segment of the crystal structure of compound 4c with the HS (dnorm), showing intermolecular conta...
Figure 7: Microscopic images of treated cells and state of the actin cytoskeleton of Sk-mel-2 cells after cul...
Figure 8: Docked view of compounds 4f, 4g, 4i, 4k, and 4l with the target protein (PDB ID: 8DNH).
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
Graphical Abstract
Scheme 1: Mechanistic overview of enzymes involved in ring-size-altering reactions: A: Difference in ionisati...
Scheme 2: A: Ring contraction through involvement of carbocationic intermediates in thujane monoterpene biosy...
Scheme 3: Examples of concerted ring expansions of carbocation intermediates in PxaTPS8-catalysed cyclisation...
Scheme 4: Sequential ring expansions during astellifadiene (17) synthesis reported by Abe and co-workers.
Scheme 5: Cyclobutane ring expansion and sequential ring contractions catalysed by the synthase AITS in the b...
Scheme 6: Ring expansion and transannular ring contraction of a cyclopentane to cyclobutane in the biosynthes...
Scheme 7: Computationally elucidated concerted cyclisations/alkyl/hydride shifts during the biosynthesis of t...
Scheme 8: Cyclisation events and 6→5-ring contraction during the construction of epi-isozizaene (26) catalyse...
Scheme 9: Transannular cyclisations and 4→5-membered ring expansion through dyotropic 1,2-rearrangement of al...
Scheme 10: Ring expansion in presilphiperfolan-8b-ol (31) biosynthesis and ring contraction of the presilphipe...
Scheme 11: Ring contraction via transannular cyclopropanation and opening of cyclopropane in the biosynthesis ...
Scheme 12: The crucial CYP450-catalysed oxidative rearrangement defining the skeleton in gibberellin biosynthe...
Scheme 13: CYP450-mediated oxidation of cyclopentane methylene expanding the 8-membered ring in the biosynthes...
Scheme 14: CYP450-mediated oxidation of an exocyclic methyl group to effect transannular cyclisation across th...
Scheme 15: Non-enzymatic transannular aldol reaction enables the formation of the 5/13/3-tricyclic ring system...
Scheme 16: A: Oxidative ring expansion of a cyclopentane by incorporation of a methyl group in the biosynthesi...
Scheme 17: Rearrangement and ring expansion in the construction of the complex bridged carbon framework of and...
Scheme 18: Ketoglutarate-mediated oxidations of preaustinoid A1 (53) en route to complex meroterpenoids, B-rin...
Scheme 19: Proposed putative biosynthetic formation of the tigliane skeleton from an E,E,Z-triene.
Scheme 20: Photocatalytic tandem ring expansion/contraction of santonin to give photosantonin products and gua...
Scheme 21: A: Proposed biosynthesis of stelleroid B (66) from stelleranoid I (65) by ketol rearrangement; B: o...
Scheme 22: Singular examples of A,B-ring contractions and expansions in the biosynthesis of sesquiterpenoids e...
Scheme 23: A: plausible proposed biosynthetic pathway for the tigliane/ingenane skeletal rearrangement and 1,2...
Scheme 24: A: Multiple ring-size alterations during xenovulene A (90) biosynthesis; B: Ring contraction and re...
Scheme 25: Proposed biosyntheses of the complex, polycyclic terpenoid illisimonin A (97) and the bridged antro...
Scheme 26: Proposed biogenetic origin for the meroterpenoid liphagal (104) via epoxide-mediated ring expansion....
Scheme 27: Proposed biogenetic origin for the ring-contracted members of the taiwaniaquinol family.
Scheme 28: A: Schenck ene/Hock/Aldol cascade effecting B-ring contraction in atheronal B (113); B: Selective C...
Scheme 29: A: D-ring expansion of buxenone (118) via cyclopropanation towards buxaustroine A (119); B: Propose...
Scheme 30: Biosynthetic origin of alstoscholarinoids A (124) and B (125) via cascade oxidative rearrangement c...
Scheme 31: Biogenetic origin of the hedgehog signalling inhibitor cyclopamine (129) by tandem ring contraction...
Scheme 32: Proposed biogenetic origin of the B-ring contracted spirocyclic triterpenoid spirochensilide A (131...
Scheme 33: A: Proposed B-ring contraction during the biosynthesis of holophyllane A (133); B: B-ring contracti...
Scheme 34: Radical and ionic/polar mechanisms for the C-ring-contracted triterpenoids phomopsterone B (139) an...
Scheme 35: A: Plausible mechanism for the formation of schiglautone A (144) from anwuweizic acid (145); B: Pro...
Scheme 36: Reported biosynthetic proposal for the formation of B-ring expanded triterpenoids rhodoterpenoids A...
Scheme 37: A: Final reaction step in the synthesis of euphorikanin A (154), benzilic acid-type ring contractio...
Scheme 38: Tricyclic ring expansion in the Gui synthesis of gibbosterol A (158) and sarocladione (160) via Ru-...
Scheme 39: A: A-ring expansion during the Gui synthesis of rubriflordilactone B (161); B: Mechanism for the bi...
Scheme 40: Photosantonin rearrangement effects A/B ring contraction/expansion in Li’s synthesis of the complex...
Scheme 41: Tandem A/B ring expansion/contraction of an ergosterol derivative via pinacol rearrangement in the ...
Scheme 42: Synthetic studies towards cyclocitrinol (179) by A) the semisynthetic approach by Gui et al. using ...
Scheme 43: A: Bioinspired synthesis of spirochensilide A (131) by the Heretsch group via selective 8,9-epoxida...
Scheme 44: Baran’s synthesis of cortistatin A (191), expanding the B-ring through a cyclopropane fragmentation....
Scheme 45: Ding’s total synthesis of retigeranic acid (198) showcasing sequential 6→5 ring contractions.
Scheme 46: A: Oxa-di-π-methane (ODPM) rearrangement of a bicyclic ketone en route to silphiperfolenone (203); ...
Scheme 47: Biomimetic synthesis of liphagal (104) from sclareolide (221) by George and co-workers.
Scheme 48: Wu’s bioinspired synthesis of cucurbalsaminones B (224) and C (225) by photocatalytic oxa-di-π-meth...
Scheme 49: Baran’s total synthesis of maoecrystal V (230) featuring a pinacol rearrangement for ring expansion...
Scheme 50: A: Ketol rearrangement leading to ring contraction in the total synthesis of preaustinoid B; B: Ben...
Scheme 51: A: Scheidt’s synthesis of isovelleral (251) by pinacol rearrangement triggered by Mitsunobu conditi...
Scheme 52: Biomimetic transformations of simplified test substrates related to Euphorbia diterpenoids.
Scheme 53: A: First generation synthesis of taiwaniaquinones by benzilic acid-type rearrangement of the B-ring...
Scheme 54: A: Norrish type 1 radical recombination leading to ring contraction en route to cuparenone (272): 1...
Scheme 55: Ring contraction of a bridged D-ring system in the total synthesis of andrastatin D (280), terrenoi...
Scheme 56: Biomimetic synthesis of hyperjapone A (284) and hyperjaponol C (285) by George et al.
Scheme 57: Heretsch’ synthesis of dankastarones A (288) and B (289), swinhoeisterol A (290), and periconiaston...
Scheme 58: A: Zhang’s ring contraction during the synthesis of stemar-13-ene (295) by pinacol rearrangement; B...
Scheme 59: Trauner’s biomimetic synthesis of preuisolactone A (307) featuring a ring contraction via benzilic ...
Scheme 60: Bioinspired approaches for ring contraction/expansion reactions in the synthesis of alstoscholarino...
Scheme 61: A: Sarpong and Li, Wang and co-workers’ ring expansion of cephanolide A (313) to reach harringtonol...
