Vinylic Position Research Articles

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.

Synthesis of 3‐CF3‐Indoles from HFO‐1234ze(E) via Cross‐Coupling and Intramolecular Cyclization

AbstractThe synthesis of indoles with a trifluoromethyl group has attracted a lot of attention because they are promising structural subunits for pharmaceuticals and agrochemicals. As part of our project aimed toward the upcycling of hydrofluoroolefins (HFOs), we developed a method to construct a CF3‐bearing indole ring system through the Suzuki–Miyaura cross‐coupling of a brominated HFO‐1234ze(E) (CF3CH=CHF) with N‐tosylated o‐borylanilines, followed by nucleophilic 5‐endo‐trig cyclization at the vinylic position of the generated fluorostyrenes. We found that the Pd2(dba)3/SPhos catalyst system in the presence of K2CO3 and water in toluene afforded the corresponding 3‐CF3‐indoles in high yields in a one‐pot operation.

Spin-Crossing in the (Z)-Selective Alkyne Semihydrogenation Mechanism Catalyzed by Mo3S4 Clusters: A Density Functional Theory Exploration.

Semihydrogenation of internal alkynes catalyzed by the air-stable imidazolyl amino [Mo3S4Cl3(ImNH2)3]+ cluster selectively affords the (Z)-alkene under soft conditions in excellent yields. Experimental results suggest a sulfur-based mechanism with the formation of a dithiolene adduct through interaction of the alkyne with the bridging sulfur atoms. However, computational studies indicate that this mechanism is unable to explain the experimental outcome: mild reaction conditions, excellent selectivity toward the (Z)-isomer, and complete deuteration of the vinylic positions in the presence of CD3OD and CH3OD. An alternative mechanism that explains the experimental results is proposed. The reaction begins with the hydrogenation of two of the Mo3(μ3-S)(μ-S)3 bridging sulfurs to yield a bis(hydrosulfide) intermediate that performs two sequential hydrogen atom transfers (HAT) from the S-H groups to the alkyne. The first HAT occurs with a spin change from singlet to triplet. After the second HAT, the singlet state is recovered. Although the dithiolene adduct is more stable than the hydrosulfide species, the large energy required for the subsequent H2 addition makes the system evolve via the second alternative pathway to selectively render the (Z)-alkene with a lower overall activation barrier.

Vinyl Halide‐Modified Unsaturated Cyclitols are Mechanism‐Based Glycosidase Inhibitors

AbstractSuitably configured allyl ethers of unsaturated cyclitols act as substrates of β‐glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of β‐glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter‐intuitive trend wherein the most electronegative substituents yielded the most labile pseudo‐glycosidic linkages. Structures of complexes with the Sulfolobus β‐glucosidase revealed similar enzyme‐ligand interactions to those seen in complexes with a 2‐fluorosugar inhibitor, the lone exception being displacement of tyrosine 322 from the active site by the halogen. Mutation of Y322 to Y322F largely abolished glycosidase activity, consistent with lost interactions at O5, but minimally affected (7‐fold) rates of carbasugar hydrolysis, yielding a more selective enzyme for unsaturated cyclitol ether hydrolysis.

Vinyl Halide-Modified Unsaturated Cyclitols are Mechanism-Based Glycosidase Inhibitors.

Suitably configured allyl ethers of unsaturated cyclitols act as substrates of β-glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of β-glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter-intuitive trend wherein the most electronegative substituents yielded the most labile pseudo-glycosidic linkages. Structures of complexes with the Sulfolobus β-glucosidase revealed similar enzyme-ligand interactions to those seen in complexes with a 2-fluorosugar inhibitor, the lone exception being displacement of tyrosine 322 from the active site by the halogen. Mutation of Y322 to Y322F largely abolished glycosidase activity, consistent with lost interactions at O5, but minimally affected (7-fold) rates of carbasugar hydrolysis, yielding a more selective enzyme for unsaturated cyclitol ether hydrolysis.

Unexplored Vinylic-Substituted 5-Benzylidenethiazolidine-2,4-diones: Synthesis and DFT/NMR Stereochemical Assignment.

By exploring an efficient and versatile method for the 6-functionalization of its scaffold, we investigated the opening of a new chemical space around benzylidenethiazolidine-2,4-dione (BTZD). The 6-chloro- and 6-formyl BTZD obtained in two steps starting from 5-lithioTZD were selected as key intermediates and involved in a Pd-catalyzed cross-coupling or Wittig olefination. A variety of aryl, heteroaryl, or alkenyl substituents was successfully introduced on the vinylic position of BTZD, and particular attention was paid to elucidate the stereochemistry of the benzylidene derivatives by using a combined DFT/NMR study.

Synthetic routes to modify hydroxyl terminated polybutadiene for various potential applications

Hydroxyl terminated polybutadiene (HTPB) is widely used in various purposes especially as a binder in the solid rocket propellant (SRP). Recent trends of modifying HTPB to be used as a binder is at high demands but structural modification without affecting core physiochemical properties of HTPB is very challenging synthetic task. In this article, we have summarized the various synthetic routes for the modification of HTPB without altering any physical properties of pristine HTPB. It was established that terminal functionalization method is extremely advantageous for maintaining all the unique properties of pristine HTPB even after other structural modification, additionally it helps to improve significantly some of the important properties of HTPB based polyurethanes. Besides, the utility of our modified HTPB based polymers has been briefly outlined here and it was shown that few of our modified HTPB based polymers are most suitable to replace HTPB completely from the propellant formulations. We also highlighted modification of HTPB by grafting polymer chains/small functional molecules in the vinylic position. Overall, this review is expected to greatly impactful for further studies in these fields.

Nucleophilic Vinylic Substitution (SNV) of Trisubstituted Monofluoroalkenes for the Synthesis of Stereodefined Trisubstituted Alkenes and Divinyl Ethers.

We herein describe a nucleophilic vinylic substitution (SNV) of trisubstituted monofluoroalkenes with excellent stereocontrol (d.r. > 99:1). Starting from (E)-β-monofluoroacrylates, various trisubstituted (E)-alkenes containing O/N/S-substituent groups at the vinylic position can be obtained under simple conditions. Furthermore, (E,E)-divinyl ethers can be generated through dimerization of the monofluoroalkenes, triggered by adventitious water in the reaction mixture.

Facile access to 2,2-diaryl 2H-chromenes through a palladium-catalyzed cascade reaction of ortho-vinyl bromobenzenes with N-tosylhydrazones.

A palladium-catalyzed cascade reaction of ortho-vinyl bromobenzenes with N-tosylhydrazones has been developed, which provides a facile approach to 2,2-disubstituted 2H-chromenes. The migration of palladium from the aryl to vinyl position is crucial, as the in situ produced vinyl palladium intermediate could further react with diazo compounds to generate the reactive species for the sequential annulation.

Electron-Transfer Ionization of Nanoparticles, Polymers, Porphyrins, and Fullerenes Using Synthetically Tunable α-Cyanophenylenevinylenes as UV MALDI-MS Matrices.

Electron-transfer ionization in matrix-assisted laser desorption/ionization (ET-MALDI) is widely used for the analysis of functional materials that are labile, unstable, and reactive in nature. However, conventional ET matrices (e.g., trans-2-[3-(4- tert-butylphenyl)-2-methyl-2-propenylidene] malononitrile (DCTB)) still lack in performance due to cluster formation, reactivity with analytes, and vacuum instability. In this contribution, we report the use of α-cyanophenylenevinylene derivatives as UV MALDI matrices for the analysis, by ET ionization, of nanoparticles, polymers, porphyrins, and fullerenes. The synthetic versatility of the phenylenevinylene (PV) core allowed us to modulate physicochemical properties, fundamental for efficient formation of primary ions in the gas phase under MALDI conditions, such as planarity, ionization potentials, molar absorptivity, and laser thresholds. For instance, introduction of -CN groups in vinyl positions of the PV core induced structural disruption in planarity in the new α-CNPV derivatives, shifting their maximum molar absorptivity to UV wavelengths and increasing their ionization energy values above 8.0 eV. UV MALDI-relevant photophysical properties in solution and solid state are reported (λmax and ε355nm). LDI spectra of α-CNPVs exhibit predominant signals due to M+• and [M + H]+ species, whereas the standard matrix DCTB shows peaks associated with clusters and nondesirable products. The mass spectrometry (MS) performance of six α-CNPV derivatives was assessed for the ionization of a standard compound, with α-CNPV-CH3 and α-CNPV-OCH3 exhibiting better analytical figures of merit than those of a standard matrix (DCTB). These new matrices display high vacuum stability (79%) for up to 240 min of residence in the ionization source, in contrast with DCTB with 13%. Vacuum stability is vital, particularly for applications such as high-throughput analysis and imaging MS. In addition, when a mixture of 20 analytes (PAHs, porphyrins, and triphenylamine dyes) ranging from m/z 300 to 1700 was analyzed via ET-MALDI, we observed analyte coverage of 90% with the α-CNPV-CH3 derivative, whereas DCTB afforded only 70%. Finally, α-CNPV-CH3 was tested and compared with DCTB, as ET-MALDI matrix for petroporphyrins, conjugated polymers, gold nanoparticles, and fullerene derivatives analysis, outperforming in most cases the standard matrix.

Functionalization at C(1) of the Dihydroazulene/Vinylheptafulvene Photo‐/Thermoswitch – Establishing Structure−Property Relationship

AbstractThe optical and switching properties of the dihydroazulene/vinylheptafulvene (DHA/VHF) photo‐/thermoswitch can be finely tuned by substituent groups at specific positions. While the kinetics of the thermal ring closure of VHF into DHA have previously been shown to follow systematic trends in regard to the electron‐withdrawing/donating character of substituents at DHA positions C(2), C(3), and C(7) (Hammett correlations), no such correlation has so far been established for a selection of compounds with different substituents at C(1). Functionalization at this position is at the same time known to have the strongest impact on the VHF‐to‐DHA conversion rate. Here we show that introduction of a benzothiazole ring at C(1) of DHA (corresponding to the vinyl position of VHF) with various electron‐withdrawing/donating groups provides VHFs whose rates of ring closure follow a Hammett correlation – the more electron‐withdrawing substituent on the benzothiazole, the faster ring closure reaction.

Experimental and Computational Study of the ( Z)-Selective Formation of Trisubstituted Olefins and Benzo-Fused Oxacycles from the Ruthenium-Catalyzed Dehydrative C-H Coupling of Phenols with Ketones.

The cationic Ru-H complex was found to be an effective catalyst for the dehydrative C-H coupling of phenols with ketones to form the trisubstituted olefin products. The coupling of phenol with linear ketones led to highly stereoselective formation of the ( Z)-olefin products. The dehydrative coupling of phenol with enones and diones efficiently formed the benzopyrene and related oxacyclic derivatives. The reaction of 3,5-dimethoxyphenol with cyclohexanone-2,2,6,6- d4 showed a significant H/D exchange to both vinyl and α-CH2 positions on the olefin product (72-75% D). A significant carbon isotope effect was observed on the ortho-arene carbon of the olefin product. The free energies of intermediate species for the entire catalytic cycle were successfully computed by using the DFT method. The DFT study revealed that the E/ Z stereoselectivity is a result of the energy difference in the insertion step of ortho-metalated phenol to an enol form of the ketone substrate (ΔΔ E = 9.6 kcal/mol). The coupling method provides a direct catalytic C-H olefination method for ketones to form trisubstituted olefins without employing any reactive reagents or forming any wasteful byproducts.

The N-Hydroxyphthalimide catalyzed oxidation of cyclohexene to cyclohexenyl hydroperoxide: Reasons for deactivation and stability of the catalyst

Selective oxidation of cyclohexene to cyclohexenyl hydroperoxide catalyzed by N-hydroxyphthalimide (NHPI) was studied. Kinetic observations and 13C and 1H NMR spectroscopy showed that accumulation of cyclohexenyl hydroperoxide was accompanied by deactivation of the catalyst. A mechanism of the deactivation through phthalimido N-oxyl radical (PINO) addition to vinyl position of olefin was suggested. Responsible for the deactivation, PINO-C6H10-OOH hydroperoxide adducts were detected in the reaction conditions, and their molecular structure was elucidated by DFT technique. The mechanism explained an unexpected experimental effect, that is, lowering the oxygen partial pressure improved the stability of NHPI without decrease in production of cyclohexenyl hydroperoxide.

Multiscale Modeling of Interfacial Oxidation Mechanism at Air/Organic Interface: Reactions of CH2═CH-Terminated Self-Assembled Monolayer with OH•, O3, and HO2•

The first few elementary steps of the reactions of a structurally characterized CH2═CH-terminated self-assembled monolayer (SAM) with reactive oxygen species, such as OH•, HO2•, and O3 were investigated using the multilayer first principle technique (ONIOM[QCISD(T)/cc-pVTZ:MP2/6-311G(d,p):BHandHLYP/6-31G(d)]//ONIOM[BHandHLYP/6-311G(d,p):BHandHLYP/6-31G(d)]) as a proxy for the interfacial oxidation mechanism on organic aerosol surfaces. The energetics of the reactions is compared with the analogous QCISD(T)/cc-pVTZ//BHandHLYP/6-311G(d,p) gas-phase results, to measure the energetic consequences of the presence of the surrounding alkene chains. All of the reactions studied are affected in such a way that the relative energies of the interfacial reactions became lower by the average value of 11.5 ± 6.1 kJ/mol than the corresponding gas-phase values. Because of this effect, interfacial H-abstractions by OH• on both allylic and vinylic positions have submerged barriers (ΔE0‡ = −5.4 kJ/mol and ΔE0‡ = −5.8 kJ/mol...

Steric-Induced Fluorescence via Methyl Substitution in Chalcone Dyes

Chemical research of luminescent dyes can have potential benefits in cell microscopy, optoelectronics and textiles. Luminescent chalcones have been studied extensively for their florescence properties and sensing capabilities, such as halochromism (pH), solvatochromism (polarity), and viscochromism (viscosity). Properties such as viscochromism can be utilized to sense the membrane viscosity in cells. To probe the viscochromic behavior of chalcones, bulky methyl-substituents were incorporated into the design of the chalcone to probe planarity, brightness and fluorescence turn-on based of environmental viscosity. This was achieved via Aldol condensation of aromatic ketones and para-(dimethylamino) benzaldehyde to incorporate a bulky methyl groups at an aromatic or vinyl positions. Synthesis of the derivatives was confirmed by 1H NMR, TLC and IR spectroscopy. Preliminary results indicate the dyes have yellow-green florescence in dichromomethane (Q.Y. ~12%), and aggregation induced emission (AIE) properties. This presentation will discuss the optical properties in solution, future directions and possible applications.

Thermal Degradation of Long Chain Fatty Acids.

The thermal hydrolysis of saturated (C16:0 and C18:0) and unsaturated fatty acids (C16:1, C18:1, and C18:2) was investigated at 90 °C to 160 °C for 30 min and 8 h durations. Hydrolysis efficiencies were calculated based on mass yield (i.e., mg/g parent compound), which accounted for all C2-C24 by-products. Very little degradation (less than 1%) of long chain fatty acids (LCFAs) was observed from 30 min thermal hydrolysis. At 140 and 160 °C for 8 h, saturated fatty acids degraded uniformly to C2 to C14. Saturated fatty acids tended to convert to alkanes (1.5-2.0% of total fatty acids) instead of fatty acids (8 h). Thermal hydrolysis did not significantly affect unsaturated LCFA degradation at any duration. The unsaturated by-products seen were the result of cleavage at the allylic or vinylic positions. Thermal hydrolysis of LCFAs with digested sludge was investigated. The amount of VFAs and LCFAs in primary and secondary sludge was increased at 140 and 160 °C as a result of lipid degradation in the sludge mixture. Thermal hydrolysis of fatty acids with different catalysts was also investigated. Whereas saturated LCFAs were stable under all catalytic conditions, unsaturated LCFAs were nearly completely degraded when hydrolyzed with hydrogen peroxide and activated carbon or copper sulfate.

Catalytic 1,2-dihydronaphthalene and E-aryl-diene synthesis via CoIII-Carbene radical and o-quinodimethane intermediates.

Catalytic synthesis of substituted 1,2-dihydronaphthalenes via metalloradical activation of o-styryl N-tosyl hydrazones ((E)-2-(prop-1-en-1-yl)benzene-N-tosyl hydrazones) is presented, taking advantage of the intrinsic reactivity of a cobalt(iii)-carbene radical intermediate. The method has been successfully applied to a broad range of substrates with various R1 substituents at the aromatic ring, producing the desired ring products in good to excellent isolated yields for substrates with an R2 = COOEt substituent at the vinylic position (∼70-90%). Changing the R2 moiety from an ester to other substituents has a surprisingly large influence on the (isolated) yields. This behaviour is unexpected for a radical rebound ring-closure mechanism, and points to a mechanism proceeding via ortho-quinodimethane (o-QDM) intermediates. Furthermore, substrates with an alkyl substituent on the allylic position reacted to form E-aryl-dienes in excellent yields, rather than the expected 1,2-dihydronaphthalenes. This result, combined with the outcome of supporting DFT calculations, strongly points to the release of reactive o-QDM intermediates from the metal centre in all cases, which either undergo a 6π-cyclisation step to form the 1,2-dihydronaphthalenes, or a [1,7]-hydride shift to produce the E-aryl-dienes. Trapping experiments using TEMPO confirm the involvement of cobalt(iii)-carbene radical intermediates. EPR spectroscopic spin-trapping experiments using phenyl N-tert-butylnitrone (PBN) confirm the radical nature of the catalytic reaction.

Synthesis, Characterization, and Alkaline Stabilities of 4-Vinylimidazolium-Based Anion Conducting Polymer Electrolyte Membranes Prepared By Radiation-Induced Grafting for Alkaline Fuel Cell Applications

There has been a growing interest in noble metal-free alkaline fuel cells, in which anion conducting polymer electrolyte membranes (AEMs) required highly alkaline durability because of high temperature and highly basic fuel cell operating condition in the fuel cells. In recent years, we have developed N-vinylimidazolium-type AEMs by radiation-induced grafting for direct hydrazine hydrate fuel cells (DHFCs).1,2 The prepared poly(N-vinylimidazolium)-grafted AEMs (NVIm-AEM) showed moderate alkaline stability, however, these AEMs degraded via the initial β-elimination at the initial stage and hydrolytic ring opening reaction of the imidazolium unit at the later stage.3 In this work, we synthesized the AEM based on a homo- and co-polymer grafts of 2-methyl-N-methyl-4-vinylimidazolium with styrene (2Me-NMe-4VIm-AEM and 2Me-NMe-4VIm/St-AEM) to prevent the β-elimination and ring opening reaction (Figure 1).According to the literature, 4-vinylimidazole (4VIm) was transformed to N-methyl-4-vinilimidazole (NMe-4VIm) by the N-methylation using sodium hydrate and methyl iodide in a 64% yield.4 NMe-4VIm was then reacted with n-BuLi and methyl iodide to give a 2-methyl-N-methyl-4-vinylimidazole monomer (2Me-NMe-4VIm) in a 56% yield (Scheme 1).The poly(ethylene-co-tetrafluoroethylene) (ETFE) films were irradiated with a 60Co γ-ray source (QST Takasaki, Gunma, Japan) at room temperature in argon atmosphere. The pre-irradiated ETFE films were immediately immersed into the argon-purged monomer solution consisting of 5.3 mol/L 2Me-NMe-4VIm or a mixture of 2Me-NMe-4VIm and St (80 : 20 molar ratio) in 1,4-dioxane. The graft reaction proceeds smoothly and gave 2Me-NMe-4VIm and 2Me-NMe-4VIm/St graft ETFE films with the grafting degree of 33% and 54%, respectively. The grafted films were then N-alkylated and ion exchanged to obtain the hydroxide from of 2Me-NMe-4VIm-AEM and 2Me-NMe-4VIm /St-AEM with IECs of 1.38 and 1.74 mmol/g (Scheme 2). The N-alkylation reaction proceeded quantitatively while the un-methylated analogue, a 4-VIm graft ETFE film, showed less reactivity and saturated at around 66% level. 2Me-NMe-4VIm-AEM and 2Me-NMe-4VIm /St-AEM showed conductivities of 175 and 157 mS/cm with water uptakes of 53 and 86%. These AEMs show significantly higher conductivities with lower water uptakes, which are desirable properties for fuel cell applications.The alkaline stability of AEMs was evaluated by the change in conductivity of AEMs in 1M KOH at 80°C. As shown in Figure 2, the conductivity of NVIm-AEM (N-vinyl type AEM) decreased to 0 mS/cm after 100 h, while 2Me-NMe-4VIm-AEM showed higher conductivities than 20 mS/cm after 100 h. The decreasing profile of the 2Me-NMe-4VIm-AEM conductivity indicates that the initial conductivity drop resulting from β-elimination was clearly suppressed by the shift of vinyl substituent from 1- to 4-positon of the imidazolium ring. Also, the decreases of conductivity at the later period, arising from ring opening degradation become much slower for 2Me-NMe-4VIm-AEM owing to the methyl substitution effect at 2-position of the imidazolium ring. The copolymer type 2Me-NMe-4VIm /St-AEM possesses excellent initial and long term alkaline stabilities. Thus, sharp drops of conductivity at the initial stage probably caused by the graft chain detachment, and the introduction of copolymerized styrene units should suppress the detachment phenomenon by hydrophobicity.5 In conclusion, for vinylimidazolium-containing graft-type AEMs, the control of vinyl position, the methyl-protection at 2-positon, and copolymerization with styrene should be promising strategy to improve the alkaline stability, which is the essential property for alkaline fuel cells.AcknowledgementThis work was supported by the Advanced Low Carbon Technology Research and Development Program (ALCA) from the Japan Science and Technology Agency (JST).

ChemInform Abstract: Synthesis of Fluorine‐Containing Exoalkylidene β‐Lactams.

AbstractPropargylic gem‐difluorides are applied to the Kinugasa reaction affording novel exoalkylidene β‐lactams with a fluorine in the vinylic position.

Fine-tuning the lifetimes and energy storage capacities of meta-stable vinylheptafulvenes via substitution at the vinyl position

A novel set of photo/thermo switches is available by one-step synthesis from the parent system.