Vinylic Position Research Articles

Synthesis of Fluorine‐Containing Exoalkylidene β‐Lactams

AbstractThe Kinugasa reaction, applied to propargylic gem‐difluorides, allows a very direct and efficient synthesis of new exoalkylidene β‐lactams with a fluorine in the vinylic position.

ChemInform Abstract: Alkynes as Allylmetal Equivalents in Redox‐Triggered C—C Couplings to Primary Alcohols: (Z)‐Homoallylic Alcohols via Ruthenium‐Catalyzed Propargyl C—H Oxidative Addition.

The cationic ruthenium catalyst generated upon the acid–base reaction of H2Ru(CO)(PPh3)3 and 2,4,6-(2-Pr)3PhSO3H promotes the redox-triggered C–C coupling of 2-alkynes and primary alcohols to form (Z)-homoallylic alcohols with good to complete control of olefin geometry. Deuterium labeling studies, which reveal roughly equal isotopic compositions at the allylic and distal vinylic positions, along with other data, corroborate a catalytic mechanism involving ruthenium(0)-mediated allene–aldehyde oxidative coupling to form a transient oxaruthenacycle, an event that ultimately defines (Z)-olefin stereochemistry.

Pd(II)-Catalyzed Allylic C–H Amination for the Preparation of 1,2- and 1,3-Cyclic Ureas

A general synthesis of 1,2- and 1,3-cyclic ureas is accomplished by intramolecular allylic C-H amination employing Pd(TFA)2/bis-sulfoxide as a catalyst. By careful modification of substrates and catalyst, a variety of 1,2-cyclic ureas are accessible from not previously employed terminal olefins substituted in allylic or vinylic positions. Furthermore, MS4A is found to be an effective additive for the synthesis of 1,3-cyclic ureas in good yields and excellent diastereoselectivities.

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.

Soluble, microporous ladder polymers formed by stepwise nucleophilic substitution of octafluorocyclopentene

A series of ladder polymers were prepared by reacting octafluorocyclopentene (OFCP) with various bisphenols at or above room temperature. The ladder polymers were synthesized in one or two steps with similar or different bisphenols due to different reactivities of fluorine atoms at vinylic (1,5) and (2,4) allylic positions of OFCP.

Alkynes as allylmetal equivalents in redox-triggered C-C couplings to primary alcohols: (Z)-homoallylic alcohols via ruthenium-catalyzed propargyl C-H oxidative addition.

The cationic ruthenium catalyst generated upon the acid–base reaction of H2Ru(CO)(PPh3)3 and 2,4,6-(2-Pr)3PhSO3H promotes the redox-triggered C–C coupling of 2-alkynes and primary alcohols to form (Z)-homoallylic alcohols with good to complete control of olefin geometry. Deuterium labeling studies, which reveal roughly equal isotopic compositions at the allylic and distal vinylic positions, along with other data, corroborate a catalytic mechanism involving ruthenium(0)-mediated allene–aldehyde oxidative coupling to form a transient oxaruthenacycle, an event that ultimately defines (Z)-olefin stereochemistry.

Carbon–Hydrogen Bond Dissociation Energies: The Curious Case of Cyclopropene

The ionization energy (IE) of the 3-cyclopropenyl radical (6.00 ± 0.17 eV) was measured in the gas phase by reacting 3-cyclopropenium cation (c-C3H3(+)) with a series of reference reagents of known IEs. This result was combined in a thermodynamic cycle to obtain the heat of formation of c-C3H3(•) (118.9 ± 4.0 kcal mol(-1)) and the allylic C-H bond dissociation energy (BDE) of cyclopropene (104.4 ± 4.0 kcal mol(-1)). These experimental values are well reproduced by high level G3 and W1 computations and reveal that the BDE is similar to that for cyclopropane and the vinyl position of cyclopropene. This is unprecedented and is a reflection of the unusual nature of cyclopropene.

Dye-sensitized Solar Cells Based on 1,3-Dithiol-2-ylidene Derivatives: Substituent and π-Spacer Effects on the Efficiency

Abstract Four novel 1,3-dithiol-2-ylidene dyes BDY-1, BDY-2, BDY-3, and BDY-4 were developed for dye-sensitized solar cells. Among these dyes, BDY-4 containing a 9,9-dibutyl-9H-fluorene spacer and a phenyl group at the vinyl position showed the highest efficiency (3.26%), indicating the importance of the phenyl substituent and the fluorene unit in improving the efficiency.

ChemInform Abstract: Selective Arylation at the Vinylic Site of Cyclic Olefins.

Cyclic olefins usually give Heck products having an aryl ring residing at the allylic or homoallylic position. We describe herein a new method that allows arylation at the vinylic position of various cyclic olefins.

ChemInform Abstract: Achieving Vinylic Selectivity in Mizoroki—Heck Reaction of Cyclic Olefins.

AbstractCyclic olefins of various ring size add aryl groups to the vinylic position with excellent selectivity using a palladium—hydride catalyst system.

Copper‐Catalyzed Trifluoromethylation‐Initiated Radical 1,2‐Aryl Migration in α,α‐Diaryl Allylic Alcohols

The trifluoromethyl (CF3) group is an important structural motif in many pharmaceutically relevant molecules because of its unique chemical and metabolic stability, lipophilicity, and binding selectivity. Consequently, much effort has been directed toward the development of efficient methods for the introduction of the trifluoromethyl group into small molecules. While a variety of processes have been reported to generate aromatic C(sp) CF3 bonds, the analogous direct trifluoromethylation of alkenes and their derivatives has received less attention. In 2011, the groups of Buchwald, Liu, and Wang independently reported efficient allylic trifluoromethylation of unactivated alkenes with copper catalysts under mild conditions. The trifluoromethylation of allylsilanes, vinyltrifluoroborates, and enamides has since been disclosed by several groups, allowing the effective formation of compounds with a CF3 group in an allylic or vinylic position. Furthermore, oxytrifluoromethylation, carbotrifluoromethylation, and hydrotrifluoromethylation of alkenes have been achieved with and without transition-metal catalysis. These reactions provide a valuable array of highly regioselective C CF3 bond-forming methods under mild conditions. However, the mechanism of these copper-catalyzed trifluoromethylation reactions is not fully understood. Addition of both the trifluoromethyl cation or radical have been suggested as routes to the observed products. Buchwald reported the efficient formation of CF3-containing epoxides from secondary allylic alcohols, possibly via intermediate A [Eq. (1)]. Thus, we envisioned that the trifluoromethylation of a,a-diaryl allylic alcohols 2 with the Togni reagent (1) would lead to the analogous intermediates B, which could undergo 1,2-aryl migration to provide btrifluoromethyl ketones 3 [Eq. (2)]. Importantly, electronrich aryl groups migrate preferentially in cationic (semipinacol) rearrangements, whereas electron-poor aryl groups migrate preferentially in radical (“neophyl”) rearrangements. Therefore, the structures of the products from unsymmetrical substrates would provide important insight into the reaction mechanism. b-Trifluoromethyl ketones such as 3 are difficult to prepare. Nucleophilic trifluoromethylating reagents typically undergo 1,2-addition to enones, affording trifluoromethyl allylic alcohols rather than b-trifluoromethyl ketones by 1,4addition. Only a few cyclic b-trifluoromethyl ketones have been prepared by 1,4-addition of a nucleophilic CF3 group to cyclic enones. The use of radical or electrophilic CF3 reagents for this challenging task has been rarely described. Consequently, we wanted to develop new C(sp) CF3 bond-forming reactions to prepare b-trifluoromethyl ketones, and to probe the mechanism of the copper-catalyzed trifluoromethylation of alkenes as discussed above. We report herein an unprecedented trifluoromethylation-initiated radical 1,2-aryl migration(“neophyl rearrangement”) in a,adiaryl allylic alcohols utilizing 1, leading to a wide variety of acyclic b-trifluoromethyl a-aryl ketones 3. We commenced our study with the reaction of 2a with the Togni reagent (1) and [(MeCN)4Cu]PF6 as catalyst (Table 1). To our delight, the reaction in methanol at 50 8C for 14 h afforded the desired rearranged product 3a in 27% yield (entry 1). It also provided 48% of compound 4a, which was probably derived by trapping of the allylic cation of 2a by MeOH. Complex product mixtures were obtained when the reaction was performed in the less nucleophilic alcohols trifluoroethanol or hexafluoroisopropanol (HFIP; entries 2 and 3, respectively). In acetonitrile and dichloromethane, mixtures of the desired ketone 3a (22% and 9%, respectively) and substitution product 4b (23% and 76%, respectively, entries 4 and 5) were formed. In DMSO, the yield of 3a increased to 51%, but the conversion was not complete (entry 6). In DMF, the yield of 3a increased further to 69% [*] X. Liu, F. Xiong, X. Huang, Prof. Dr. X. Wu Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences 190 Kaiyuan Avenue, Guangzhou 510530 (China) E-mail: wu_xiaoxing@gibh.ac.cn

Achieving Vinylic Selectivity in Mizoroki–Heck Reaction of Cyclic Olefins

In Heck reactions of cyclic olefins, the products usually have aryl groups that end up at the allylic and/or homoallylic position. We herein report new selectivity that adds aryl groups to the vinylic position. Cyclic olefins of various ring size worked well. The desired isomers were produced by palladium-hydride-catalyzed isomerization of the initial products. Thus, a specific catalyst must be used so that it can perform two jobs under one set of reaction conditions.

Vinylic substitution in the reaction of betulin diacetate with tert-butyl hypochlorite

Unlike unsaturated compounds containing alkyl groups at the double bond, low-temperature chlorination of betulin diacetate with tert-butyl hypochlorite involves mainly replacement of hydrogen in the vinylic position to give Z- and E-isomeric chlorides and a small amount of the allylic isomer, the latter resulting from elimination of hydrogen from the C30H3 group.

Selective arylation at the vinylic site of cyclic olefins

Cyclic olefins usually give Heck products having an aryl ring residing at the allylic or homoallylic position. We describe herein a new method that allows arylation at the vinylic position of various cyclic olefins.

Insights on the mechanistic features of catalytic oxidations of simple and conjugated olefins promoted by VO(acac)2/H2O2 system, in acetonitrile: A computational study

A computational study based on standard Density Functional Theory and polarized continuum model has been carried out for investigating the essential mechanistic features occurring in the catalytic oxidation of two model substrates, namely ethylene and 1,3-butadiene, promoted by vanadyl acetylacetonate [VO(acac)2] in the presence of hydrogen peroxide. Results, showing in general a qualitative agreement with experimental data carried out on more complex systems, provide quite different scenarios depending on the conditions employed for the reaction. In particular, under thermodynamic control, no selectivity is observed between the two competitive routes, either epoxidation or double bond oxidative cleavage, in both the substrates. On the other hand, under kinetic control, in both systems the double bond oxidative cleavage is always the favored path, although in the case of 1,3-butadiene the difference with the epoxidation route is enhanced, this confirming that the selectivity is sensitive to the nature of the substituent in the vinyl position.

Conformational control of TTFV π-frameworks through naphthyl substituents

With 1- or 2-naphthyl substituted at the vinyl positions, the conformation of the tetrathiafulvalene vinylogue π-framework can be greatly modified from completely planar to highly twisted, and the structural changes lead to markedly different electronic and electrochemical behaviours.

Mechanism of gold(I)-catalyzed rearrangements of acetylenic amine-N-oxides: computational investigations lead to a new mechanism confirmed by experiment.

Quantum mechanical studies of the mechanism of gold-catalyzed rearrangements of acetylenic amine-N-oxides to piperidinones or azepanones have revealed a new mechanism involving a concerted heteroretroene reaction, formally a 1,5 hydrogen shift from the N-alkyl groups to the vinyl position of a gold-coordinated methyleneisoxazolidinium or methyleneoxazinanium. Density functional calculations (B3LYP, B3LYP-D3) on the heteroretroene mechanism reproduce experimental regioselectivities and provide an explanation as to why the hydrogen is transferred from the smaller amine substituent. In support of the proposed mechanism, new experimental investigations show that the hydrogen shift is concerted and that gold carbenes are not involved as reaction intermediates.

Indirect Iodination on the Vinyl Double Bond of Andrographolide

Andrographolide is a bicyclic diterpenoid constituent of Andrographis paniculata which is used extensively in the traditional medicine in Indonesia to treat inflammations. The structure of andrographolide contains an a-alkylidene r-butyrolactone moiety, two olefin bonds at C-8(C-17) and C-12(C-13), and three hydroxyls at C-3, C-19 and C-14. Andrographolide's structure lacks of aromatic ring, hence the iodination reaction of this compound is quite an interesting challenge to be investigated. Iodine atom was incorporated at vinyl position by indirect reaction. The reaction was divided into two steps, which was started by a bromination in non polar medium, then followed by iodination. It is shown that the principal reaction is the addition of bromine atom to an sp2 carbon atom of the vinyl group via electrophilic substitution. Bromination was carried out in chloroform solvent at room temperature to produce bromo-andrographolide. The iodination was applied further by using palladium triphenylphosphine catalyst. Positive charge iodine species was produced in situ with the addition of chloramine-T, an oxidizing agent, at 40 oC. 1H-NMR study shows that iodine attacked the C-12(C-13) vinyl bond which was confirmed by (1) the disappearance of proton chemical shift of C-12 at SH 6.86 ppm and (2) the change of proton chemical shifts of C-11 which shifted downfield at SH 2.74 ppm and 2.63 ppm, due to the deshielding effect of iodine.

Rationalizing the Effect of Halogenation on the Molecular Structure of Simple Cyclobutene Derivatives by Topological Real-Space Analysis of Their Electron Density

The accurate gas-phase equilibrium structures on the ground-state potential energy surface of the complete series of fluorinated and chlorinated cyclobutene derivatives with C(2v) symmetry have been evaluated at DFT PBE0/6-311++G(d,p) theory level. The optimized geometries have been compared with all the available experimental data reported in the literature, as obtained by microwave spectroscopy (MW) and gas-phase electron diffraction (GED) techniques. For hexafluorocyclobutene and 1,2-dichloro-3,3',4,4'-tetrafluorocyclobut-1-ene, the results of accurate low-temperature single-crystal X-ray diffraction experiments have also been considered. Structural changes within the cyclobutene ring, as induced by fluorination and chlorination at allylic and vinylic positions, have been correlated with changes in the corresponding theoretical charge densities. To this aim, several local and nonlocal topological descriptors provided by the quantum theory of atoms in molecules, QTAIM, have been employed, with particular emphasis on the delocalization indices and integrated source function decomposition schemes. Key factors for the resulting molecular structures are the chemical nature and the steric hindrance of the substituents, as well as quantum-mechanical effects, such as delocalization and partial conjugation. When fluorine atoms replace hydrogens at allylic or vinylic positions, the corresponding Csp(3)-Csp(3) or Csp(2)═Csp(2) bonds between the substituted carbons undergo a significant strengthening, while chlorination has just the opposite effect. In the latter case the steric hindrance between bulky chlorine atoms occupying vicinal positions is crucial in determining the single Csp(3)-Csp(3) bond length. These findings are discussed in the context of the reactivity of chemically related chlorofluorocarbon compounds.

Amplification of Anti-Diastereoselectivity via Curtin−Hammett Effects in Ruthenium-Catalyzed Hydrohydroxyalkylation of 1,1-Disubstituted Allenes: Diastereoselective Formation of All-Carbon Quaternary Centers

Under the conditions of ruthenium-catalyzed transfer hydrogenation, 1,1-disubstituted allenes 1a-c and alcohols 2a-g engage in redox-triggered generation of allylruthenium-aldehyde pairs to form products of hydrohydroxyalkylation 3a-g, 4a-g, and 5a-g with complete branched regioselectivity. By exploiting Curtin-Hammett effects, good to excellent levels of anti-diastereoselectivity (4:1 to >20:1) are obtained. Thus, all carbon quaternary centers are formed in a diastereoselective fashion upon carbonyl addition from the alcohol oxidation level in the absence of premetalated nucleophiles or stoichiometric byproducts. Exposure of allene 1b to equimolar quantities of alcohol 2a and aldehyde 6b under standard reaction conditions delivers adducts 4a and 4b in a 1:1 ratio. Similarly, exposure of allene 1b to equimolar quantities of aldehyde 6a and alcohol 2b provides adducts 4a and 4b in an identical equimolar ratio. Exposure of allene 1b to d(2)-p-nitrobenzyl alcohol, deuterio-2a, under standard reaction conditions delivers the product of hydrohydroxyalkylation, deuterio-4a, which incorporates deuterium at the carbinol position (>95% (2)H) and the interior vinylic position (34% (2)H). Competition experiments involving exposure of allene 1b to equimolar quantities of benzylic alcohols 2a and deuterio-2a reveal no significant kinetic effect. The collective data corroborate rapid, reversible alcohol dehydrogenation, allene hydrometalation, and (E)-, (Z)-isomerization of the transient allylruthenium in advance of turnover-limiting carbonyl addition. Notably, analogous allene-aldehyde reductive C-C couplings employing 2-propanol as the terminal reductant display poor levels of anti-diastereoselectivity, suggesting that carbonyl addition is not turnover-limiting in reactions conducted from the aldehyde oxidation level.