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.
