Vinyl Bromide Research Articles

Pd-Catalyzed Tandem Approach for 1,2,3-Triazolo-azepine Fused Benzosuberenes and 1,2,3-Triazolobenzazepines Synthesis.

Herein, a highly efficient palladium-catalyzed tandem approach for the synthesis of 1,2,3-triazolo-azepine-fused benzosuberenes (TAABS) has been developed for the first time with vinyl bromide and internal alkynes as starting precursors. The given reaction proceeded under ligand- and additive-free conditions via sequential carbopalladation, followed by intramolecular electrophilic substitution. Also, the developed protocol has good functional group tolerance, wherein a range of sterically hindered TAABS analogues has been synthesized in appreciable yields. In addition, the developed methodology was also extended for the synthesis of 1,2.3-triazolobenzazepines from triazole-bearing aryl iodides and internal alkynes. The present protocol operates under relatively milder conditions with comparatively shorter reaction time. Furthermore, computational studies were also performed to validate the proposed mechanistic pathways. Additionally, the developed protocol is applicable to the gram-scale synthesis of TAABS analogues.

Total syntheses of cyclohelminthol I-IV reveal a new cysteine-selective covalent reactive group.

Biocompatible covalent reactive groups (CRGs) play pivotal roles in several areas of chemical biology and the life sciences, including targeted covalent inhibitor design and preparation of advanced biologic drugs, such as antibody-drug conjugates. In this study, we present the discovery that the small, chlorinated polyketide natural product cyclohelminthiol II (CHM-II) acts as a new type of cysteine/thiol-targeting CRG incorporating both reversible and irreversible reactivity. We devise the first syntheses of four simple cyclohelminthols, (±)-cyclohelminthol I-IV, with selective chlorinations (at C2 and C5) and a Ni-catalyzed reductive cross coupling between an enone, a vinyl bromide and triethylsilyl chloride as the key steps. Unbiased biological profiling (cell painting) was used to discover a putative covalent mechanism for CHM-II in cells with subsequent validation experiments demonstrating mechanistic similarity to dimethyl fumarate (DMF) - a known (covalent) drug used in the treatment of multiple sclerosis. Focused biochemical experiments revealed divergent thiol-reactivity inherent to the CHM-II scaffold and through further chemical derivatization of CHM-II we applied activity-based protein profiling (ABPP)-workflows to show exclusive cysteine-labelling in cell lysate. Overall, this study provides both efficient synthetic access to the CHM-II chemotype - and neighboring chemical space - and proof-of-concept for several potential applications of this new privileged CRG-class within covalent chemical biology.

Nickel-Catalyzed Direct Fluorosulfonylation of Vinyl Bromides and Benzyl Bromides for Sulfonyl Fluorides.

An efficient nickel-catalyzed direct fluorosulfonylation of vinyl bromides and benzyl bromides under mild reaction conditions has been developed for sulfonyl fluorides utilizing Na2S2O4 and NFSI as the sulfur dioxide and fluorine sources, respectively. This reaction system tolerates organic bromide compounds, such as β-styryl bromides, alkyl vinyl bromides, and benzyl bromides, to achieve corresponding sulfonyl fluorides in moderate to good yields, with convenient operation, mild conditions, broad substrate scope, good functional group compatibility, and excellent retention of configuration to vinyl bromides.

Concise Asymmetric Total Syntheses of (+)-Dihydropleurotinic Acid and (-)-Pleurotin, Enabling Rapid Late-Stage Diversification.

(-)-Pleurotin (1) and (+)-dihydropleurotinic acid (2) are benzoquinone meroterpenoids isolated from fungal sources with powerful antitumor and antibiotic activities. Concise asymmetric total syntheses of the stereochemically pure (+)-dihydropleurotinic acid (2) and (-)-pleurotin (1) from the chiral pool (R)-Roche ester-derived vinyl bromide 7 have been achieved in 12 and 13 longest linear steps, respectively. The key transformations feature a Michael addition/alkylation cascade reaction to forge three contiguous stereocenters matched with the natural products, a PtO2-catalyzed stereoselective reduction of olefin to generate the correct stereocenter at C3, a palladium-catalyzed Negishi cross-coupling between triflate and zinc reagent to introduce the redox-sensitive para-quinone moiety, and a hydroboration/copper-catalyzed carboxylation sequence to incorporate the vital carboxyl group. Thus, the highly efficient and scalable preparation of pleurotin's pentacyclic skeleton enables the late-stage diversification, affording otherwise unavailable pleurotin analogs with significantly improved antiproliferative activities against the thioredoxin reductase (TrxR) overexpressed human breast cancer cell lines relative to the natural product pleurotin (1).

Nickel-Catalyzed Cross-Electrophile Vinylation of α-Chloro Phosphonates.

Herein, we report a general and efficient Ni-catalyzed reductive cross-coupling reaction of substituted vinyl bromides and α-chloro phosphonates to access a set of α-vinyl phosphonates using zinc as the terminal reductant. This reaction exhibits broad substrate adaptability and good functional group tolerance, which allows to afford diverse compounds including structurally complex motifs from natural products and drugs. Furthermore, the practicality was certificated through the gram-scale and transformation experiments. The preliminary mechanistic investigations support a radical chain process. The potential to realize enantiomeric control makes it more valuable for further exploration.

1,2,3-Triazole-Guided Multi-Component Sonogashira Coupling of Substituted Benzosuberenes Derived from Cedrus deodara Oil

AbstractHerein, Sonogashira coupling at the vinyl bromide position of triazole-bearing benzosuberene has been introduced for the synthesis of potentially bioactive 1,2,3-triazole and conjugated enynes containing benzosuberene analogues. The instalment of triazole moiety on the allylic position dictates the Sonogashira coupling at the vinylic position, the absence of which failed to execute the desired reaction. The Cu-catalyzed cycloaddition initially led to the incorporation of 1,2,3-triazole, which subsequently directed the Pd/Cu-catalyzed Sonogashira coupling to deliver new class of benzosuberene analogues in appreciable yields. The regioselective synthesis of 1,2,3-triazole and conjugated enynes containing benzosuberene analogues has been reported under operationally simple and milder reaction conditions.

Palladium‐Catalyzed C−H Alkenylation of α‐Aryl Alkyl Nitriles

AbstractA direct α‐alkenylation of nitrile compounds was realized with a palladium complex. This method exhibited excellent tolerance toward a variety of α‐aryl alkyl nitriles and vinyl bromides, leading to the formation of a series of α‐quaternary nitriles containing vinyl groups. Further manipulations of the obtained products were demonstrated, highlighting the potential synthetic utility of this method.

Synthesis of Styrenes and E‐Stilbenes by Palladium‐Catalyzed Vinylation of Aryl Iodides with 1,2‐Dibromoethane

AbstractThe Pd‐catalyzed vinylation reactions of aryl iodides using 1,2‐dibromoethane is developed for the synthesis of styrenes and stilbenes. In these reactions, vinyl bromide is generated from 1,2‐dibromoethane and then undergoes reductive cross‐coupling with aryl iodides, affording styrene products. Under slightly modified reaction conditions, styrenes can continue reacting with vinyl bromide to form E‐stilbenes, which provides a one‐pot synthetic method for stilbenes. Alcohols, including iso‐propanol and methanol, are employed as the reductant in these reductive cross‐coupling reactions.

Electrochemical Reductive Cross-Coupling of Vinyl Bromides for the Synthesis of 1,3-Dienes.

An electroreductive cross-electrophile coupling protocol was developed for the construction of valuable 1,3-dienes from vinyl bromides. Furthermore, this scalable method can also be used to forge complex [4 + 2] cycloadducts in a one-pot manner. One of the most important advantages of this green and sustainable protocol is the in situ release of nickel catalyst from the inexpensive electrodes without the addition of extra harmful metal catalysts and reductant.

Comparative Computational Study on Molecular Structure, Electronic and Vibrational Analysis of Vinyl Bromide based on HF and DFT Approach

In this study, we have used the Hartree-Fock and Density Functional Theory method of calculation and compared the equilibrium configuration, electronic and vibrational mode of Vinyl Bromide molecule. The molecule is geometrically optimized initially by using 6-31G basis set with B3LYP functional and then bond angles, bond lengths, dihedral angles and IR spectra are compared respectively. Various groups of atoms in Vinyl Bromide molecule by DFT has more accurate bond length, bond angle values rather than by HF computation when comparing with the experimental values. The ground state energies are found at angle 10° or 180° or 360° using HF and DFT method of calculation for the H4-C1-C2-Br6 position. Values of the carbon-hydrogen, carbon-carbon and carbon-bromine bond lengths and bond angles for optimization state of C2H3Br molecule using Hartree-Fock and Density Functional Theory methods with respect to the basis set 6-31G have been analyzed. The C−H in-plane bending vibration and C−H out-of-plane bending vibrations occur in the region 1400–1050 cm-1 and 1000–675 cm-1 respectively. The electronic properties, such as Highest Occupied Molecular Orbital and Lowest Unoccupied Molecular Orbital energies are performed by HF and DFT approach and the difference in Highest Occupied Molecular Orbital and Lowest Unoccupied Molecular Orbital energy gap for HF and DFT method are 14.0847 eV and 6.8994 eV respectively

Formal Total Synthesis of Batrachotoxin Enabled by Radical and Weix Coupling Reactions.

Batrachotoxin (1), originally isolated from a Columbian poison-dart frog, is a steroidal alkaloid. Its 6/6/6/5-membered carbocycle (ABCD-ring) contains two double bonds, one nitrogen, and five oxygen functionalities. We developed a radical-based convergent strategy and realized the total synthesis of 1 in 28 steps. The AB-ring and D-ring fragments were efficiently synthesized and linked by exploiting a powerful Et3B/O2-mediated radical coupling reaction. Vinyl triflate and vinyl bromide were then utilized for a Pd/Ni-promoted Weix coupling reaction to cyclize the C-ring. A hydroxy group of the C-ring was stereoselectively installed by a decarboxylative hydroxylation reaction to prepare an advanced intermediate of our previous total synthesis of 1.

Vinyl Esters and Vinyl Sulfonates as Green Alternatives to Vinyl Bromide for the Synthesis of Monosubstituted Alkenes via Transition-Metal-Catalyzed Reactions

This review summarizes the applications of vinyl sulfonate and vinyl acetate as green alternatives for vinyl bromide in cross-coupling reactions. In the first part, the preparation of vinyl sulfonates and their cross-coupling reactions are briefly discussed. Then, a brief review of vinyl acetate cross-coupling reactions, including cyclization reactions, the Fujiware–Moritani reaction, and transvinylation reactions are described.

Collisional Relaxation of Highly Vibrationally Excited Acetylene Mediated by the Vinylidene Isomer.

Collisional relaxation of highly vibrationally excited acetylene, generated from the 193 nm photolysis of vinyl bromide with roughly 23,000 cm-1 of nascent vibrational energy, is studied via submicrosecond time-resolved Fourier transform infrared (FTIR) emission spectroscopy. IR emission from vibrationally hot acetylene during collisional relaxation by helium, neon, argon, and krypton rare-gas colliders is recorded and analyzed to deduce the acetylene energy content as a function of time. The average energy lost per collision, ⟨ΔE⟩, is computed using the Lennard-Jones collision frequency. Two distinct vibrational-to-translational (V-T) energy transfer regimes in terms of the acetylene energy are identified. At vibrational energies below 10,000-14,000 cm-1, energy transfer efficiency increases linearly with molecular energy content and is in line with typical V-T behavior in quantity. In contrast, above 10,000-14,000 cm-1, the V-T energy transfer efficiency displays a dramatic and rapid increase. This increase is nearly coincident with the acetylene-vinylidene isomerization limit, which occurs nearly 15,000 cm-1 above the acetylene zero-point energy. Combined quasi-classical trajectory calculations and Schwartz-Slawsky-Herzfeld-Tanczos theory point to a vinylidene contribution being responsible for the large enhancement. This observation illustrates the influence of energetically accessible structural isomers to greatly enhance the energy transfer rates of highly vibrationally excited molecules.

Nickel/Copper Co‐catalyzed Enantioselective Reductive Coupling of Oxabenzonorbornadienes with Vinyl Bromides

AbstractThe enantioselective reductive coupling of oxabenzonorbornadiene with vinyl bromide is developed with earth‐abundant nickel catalyst with copper as Lewis acid co‐catalyst. The asymmetric reductive coupling is applicable with a wide range of azabenzonorbornadienes and vinyl bromides under nickel/copper co‐catalytic system, affording the cis ring‐opening vinylation products in good yields with high optical purities. The present study has enabled straightforward stereoselective preparation of chiral 2‐vinyl‐tetrahydronaphthalens from vinyl halides.

Synthesis of chiral allylic phosphonates via asymmetric reductive cross-coupling of α-bromophosphonates and vinyl bromides

Synthesis of chiral allylic phosphonates via asymmetric reductive cross-coupling of α-bromophosphonates and vinyl bromides

Strong-field photoionization/dissociation of vinyl bromide in near-infrared and ultraviolet femtosecond laser fields

Ionization of polyatomic molecules in strong femtosecond laser fields is a pivotal process that may induce a variety of highly nonlinear molecular physical phenomena. We performed an experimental study on photoionization and dissociation of vinyl bromide molecules in 800 nm or 400 nm femtosecond strong laser fields using a time-of-flight mass spectrometer. The dependence of the ion yields on laser intensity and polarization was investigated, and the results are compared in different wavelength laser fields. The kinetic energy releases from Coulomb explosion of vinyl bromide, and the angular distributions of different fragment ions were obtained. The mechanism of strong-field ionization/dissociation of vinyl bromide in different laser fields is discussed based on the experimental results.

Synthesis of linear and branched poly(phenylacetylene)s through Mizoroki-Heck coupling reaction of vinyl bromides

Polyacetylene and its derivatives are a class of traditional conjugated polymers that started the era of conducting plastics. In this paper, we develop a new approach of synthesizing substituted poly(phenylacetylene)s through Mizoroki-Heck coupling of vinyl bromides. A series of α-bromostyrene derivatives are synthesized and used as the monomers for the polycoupling reaction. It is found that K2CO3 is the effective base while Et3N shows almost no catalytic reactivity. Gel permeation chromatography (GPC) results indicate that the molecular weight distribution is broad, which is typical for step growth polymerization. A kinetic study shows that electron withdrawing group on the phenyl ring increase the polymerization rate of the corresponding monomer. Furthermore, incorporating both aryl and vinyl halides into a single vinyl monomer allows the synthesis of branched polyacetylene possessing oligo(phenylene vinylene) at the branch points. The current approach may serve as a new tool for the molecular engineering of substituted polyacetylene materials.

Cutting Me Off: Selective N-Demethylation of Trialkylamines Using C(sp2)–Bromides as HAT Reagents

Key words aryl bromides - hydrogen atom transfer - N-demethylation - nickel catalysis - photoinduced catalysis - trialkylamines - vinyl bromides

Bromine-Radical-Mediated Bromoallylation of C–C Unsaturated Bonds: A Facile Access to 1,4-, 1,5-, 1,6-, and 1,7-Dienes and Related Compounds

AbstractThe radical bromoallylation of alkynes, allenes, and vinylidene cyclopropanes proceeds efficiently in the presence of a radical initiator to give 2-bromo-substituted 1,4-, 1,5-, and 1,6-diene derivatives, respectively. Three-component reactions comprised of allenes, electron-deficient alkenes, and allyl bromides give 1,7-dienes in good yields. The bromoallylation of an arylalkene can override β-scission of the bromine radical from β-bromoalkyl radicals to give 5-bromoalkenes, whilst the bromoallylation of vinylcyclopropanes is accompanied by 5-exo ring closure to give 1-(bromomethyl)-2-vinylcyclopentane derivatives in good yields. All of the products contain a reactive vinyl bromide moiety, which can be readily functionalized by Pd-catalyzed cross-coupling and radical cascade reactions.1 Introduction2 Synthesis of 1,4-Dienes by Bromoallylation of Acetylenes3 Synthesis of 1,5-Dienes by Bromoallylation of Allenes4 Synthesis of 1,6-Dienes by Bromoallylation of Methylenecyclopropanes5 Synthesis of 1,7-Dienes by Bromoallylation of Allenes and Electron-Deficient Alkenes6 Bromoallylation of Arylalkenes and Vinylcyclopropanes7 Conclusion

Passivation of poly-Si surface using vinyl and epoxy group additives for selective Si3N4 etching in H3PO4 solution

This work investigates the mechanism of polycrystalline silicon (poly-Si) dissolution in H3PO4. The etching rate of poly-Si was more rapid than that of silicon dioxide (SiO2) in H3PO4 solution, because poly-Si surface possesses unstable Si1+, Si2+, and Si3+ states – rather than Si4+, which is more stable. Additives such as epichlorohydrin, 1,2-epoxy-3-phenoxypropane, vinyl bromide, and phenyl vinyl ether with epoxy or vinyl groups were introduced into the H3PO4 to passivate the poly-Si surface. This significantly increased the presence of the Si4+ state and provided hydrophobic functional groups on the poly-Si surface to reduce the wettability of the poly-Si surface. The introduction of these additives significantly reduced the etching rate of poly-Si. 3-glycidyloxypropyl trimethoxysilane, 3-glycidyloxypropyl dimethoxymethylsilane, allyltrimethoxysilane, and vinyltrimethoxysilane with Si–O bonds, as well as epoxy or vinyl groups in their molecular structures, were demonstrated to suppress the etching rate of both SiO2 and poly-Si. The introduction of these additives to H3PO4 promoted the selective removal of silicon nitride (Si3N4) layers from multi-layered Si3N4/SiO2 trench structures without the loss of either poly-Si or SiO2.