Theoretical study of bimolecular elimination (E2) reactions. Possibility ofsyn E2 elimination in the series of 2-R-2-R'-1-halocyclopropanes

Reactions of the methoxide ion with substituted halocyclopropanes, which result in E2 elimination, have been studied by the semiempirical quantum-chemical AM1 method. The transition states corresponding totrans andcis routes have been localized. The energetic predominance of thetrans route over thecis route is reduced by 2.6 kcal mol^–1 on going from 1-chloropropane to chlorocyclopropane because of the features of cyclopropane geometry. It has been demonstrated that, in the gas phase,cis elimination may predominate overtrans elimination for a particular stereoisomer of 2-cyano-2-methyl-1-halocyclopropanes due to weakening of orbital interactions and Coulomb repulsion between the cyano group and the MeO^– anion in thetrans E2 transition state.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 620–623, April, 1995.     

Sterically demanding bis(2-silylindenyl)zirconium(IV) dichlorides as polymerisation catalyst precursors

A set of different 1- and 2-silyl-substituted zirconocene dichloride/MAO catalyst systems was investigated with respect to their performance in ethene/1-hexene copolymerisations. In-depth studies of bis(2-dimethylsilylindenyl) zirconium(IV) dichloride ( 1 ) revealed a multi-site behaviour, illustrating sensitivity to the reaction temperature and the comonomer mole fraction. Surprisingly, an upper limit is observed for the latter, leading to complete catalyst inhibition. Analysis of the chain termination processes implies the possibility of a predominant, although in general less favourable, β-hydride elimination route under certain polymerisation conditions.     

Mechanism of Silver(I)‐Catalyzed Enantioselective Synthesis of Axially Chiral Allenes Based on Propargylamines

The silver(I)‐catalyzed synthesis picture of axially chiral allenes based on propargylamines has been outlined using density functional theory (DFT) method for the first time. Our calculations find that, the coordination of silver(I) into triple bond of propargylamines at anti‐position of nitrogen shows a stronger activation on the triple bond than that at cis‐position, which is favorable for the subsequent hydrogen transfer. The NBO charge analysis for the hydrogen transfer affirms the experimental speculation that this step is a hydride transfer process. The energy barrier of the anti‐periplanar elimination of vinyl‐silver is 26.9 kJ·mol^?1 lower than that of the syn‐periplanar elimination, supporting that (?)‐allene is the main product of this reaction. In a word, the most possible route for this reaction is that the silver(I) coordinates into the triple bond of propargylamines at anti‐position of nitrogen, then the formed silver(I) complex undergoes a hydride transfer to give a vinyl‐silver, finally the vinyl‐silver goes through an anti‐periplanar elimination to give (?)‐allene. The hydride transfer with the energy barrier of 44.8 kJ·mol^?1 is the rate‐limiting step in whole catalytic process. This work provides insight into why this reaction has a very high enantioselectivity.     

Hetero Diels–Alder Cycloaddition of Indene for the Formal Synthesis of Onychnine

A highly regio‐ and stereoselective hetero Diels–Alder cycloaddition of indene with N‐sulfonyl‐1‐aza‐1,3‐butadiene was achieved. Subsequent transformation of the 5H‐indeno [l,2‐b]pyridine via elimination and reduction provides a new route to azafluorenone (e.g., 1‐methyl‐4‐azafluorene) for the synthesis of onychnine.     

Enantiospecific Synthesis and Cytotoxicity Evaluation of Ligudentatol: A Programmed Aromatization Approach to the 2,3,4‐Trisubstituted Phenolic Motif via Visible‐Light‐Mediated Group Transfer Radical Cyclization

A facile enantiospecific approach to (+)‐ligudentatol ( 1 ) and (?)‐ligudentatol (ent‐ 1 ) is reported. The approach features the construction of a trisubstituted phenolic motif fused to a chiral aliphatic ring by a sequence of visible‐light‐mediated radical seleno transfer cyclization, bromination, concomitant selenoxide elimination–dehydrobromination, and demethoxycarbonylation, namely, a programmed aromatization. Biological evaluation of the enantiomers of ligudentatol obtained by the present route revealed for the first time their cytotoxicity towards various cancer cell lines.     

Synthetic Studies on Coenzyme Q10. Part 2

An improved route to coenzyme Q₁₀ ( 1 ) starting from commercially available coenzyme Q₁ is described. The key steps in this synthesis are the SeO₂‐mediated oxidation of the protected isoprenylhydroquinone 3 into the (E)‐allyl alcohol 5 without the formation of undesired stereoisomer and the one‐pot reductive elimination of the phenylsulfonyl and dibenzyl groups in 7 by using naphthalenyllithium.     

The Gas-Phase Thermal Decomposition of 5-Ethyl-1-pyrroline

The gas-phase thermal decomposition of 5-ethyl-1-pyrroline has been studied in the temperature range 721–786 K. The decomposition appears to proceed by two pathways, one a radical route yielding pyrrole, ethylene and ethane as major products, and the other a molecular hydrogen elimination to form initially 2-ethyl-3H-pyrrole which rapidly rearranges to other ethylpyrroles via a series of 1,5-hydrogen shifts. Approximate rate constants for the unimolecular hydrogen elimination have been calculated and fit the Arrhenius relationship: Approximate calculations based on the radical pathway yield a value of ～14 kcal mol^?1 for the stabilization energy in the 1-pyrrolin-5-yl radical, in good agreement with that reported earlier for the substituted 2-aza-allyl radical.     

Direct Synthetic Route to Functionalized 1,2‐Azaborinines

A new catalytic synthetic route to functionalized 1,2‐azaborinines has been developed by the [2+2]/[2+4] cycloaddition reactions of di‐tert‐butyliminoboranes and alkynes in presence of a rhodium catalyst. The first examples of ferrocene‐functionalized azaborinines have been synthesized using this strategy. Moreover, the regioselectivity of this reaction can be controlled by the formation of an intermediate rhodium 1,2‐azaborete complex, which results in the isolation of the first azaborinine boronic ester. The isolation of an NH‐containing BN isostere by elimination of isobutene from an N(tBu) group under thermolytic conditions has also been achieved. Theoretical studies give further insight into the formation of 1,2‐azaborinines and the elimination of isobutene from the N(tBu) group.     

Hydrogen migrations in mass spectrometry. VI—the chemical ionization mass spectra of substituted benzoic acids and benzyl alcohols

The H₂ and CH₄ chemical ionization mass spectra of a series of series of substituted benzoic acids and substituted benzyl alcohols have been determined. For the benzoic acids the major fragmentation reactions of the protonated molecule involve elimination of H₂O or elimination of CO₂, the latter reaction involving migration of the carboxylic hydrogen to the aromatic ring. For the benzyl alcohols the major fragmentation reactions of [MH]⁺ involve loss of H₂O or CH₂O, analogous to the CO₂ elimination reaction for the benzoic acids. It is shown that the CO₂ and CH₂O elimination reactions occur only when a conjugated aromatic ring system is present, and that for the carboxylic acid systems, methyl groups and, to a lesser extent, phenyl groups are capable of migrating. The only discernible effect of substituents on the fragmentation of [MH]⁺ is an enhancement of the H₂O loss reaction in the benzoic acid system when an amino, hydroxyl, or halogen substituent is ortho to the carboxyl function. This ‘ortho’ effect, which differs in scope from that observed in electron impact mass spectra, is attributed to an intramolecular catalysis by the ortho substituent of the 1,3 hydrogen migration in the carbonyl protonated acid followed by H₂O elimination. Apparently, this route is favoured over the direct elimination of H₂O from the carbonyl protonated acid, since the latter has a high activation energy barrier because of unfavourable orbital symmetry restrictions.     

A new synthetic route to 7-halo-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid,an intermediate for the synthesis of quinolone antibacterial agents

Starting from m-fluorotoluene, 7-chloro-6-fluoro- and 6,7-difluoro-1-cyclopropyl-1,4-dihydro-4-oxoquino-line-3-carboxylic acids, 3 and 16 were synthesized. Compounds 3 and 16 are useful intermediates for the synthesis of a class of quinolone antibacterial agents. The synthetic route involves two processes; i) construction of the quinoline ring by an intramolecular cyclization accompanied by the elimination of a nitro group and ii) introduction of fluorine atom by replacement of a nitro group with potassium fluoride. 7-(3-Amino-1-pyrroli-dinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (18) was prepared from 3 or 16. The antibacterial activity of 18 compares favorably with that of ciprofloxacin (2) .     

Synthesis of unsaturation containing P(VDF‐co‐TrFE‐co‐CTFE) from P(VDF‐co‐CTFE) in one‐pot catalyzed with Cu(0)‐based single electron transfer living radical polymerization system

Poly(vinylidene fluoride‐co‐trifluoroethylene‐co‐chlorotrifluoroethylene) (P(VDF‐co‐TrFE‐co‐CTFE)) with internal double bond has been reported with high dielectric constant and energy density at room temperature, which is expected to serve as a promising dielectric film in high pulse discharge capacitors. An environmentally friendly one‐pot route, including the controllable hydrogenation via Cu(0) mediated single electron transfer radical chain transfer reaction (SET‐CTR) and dehydrochlorination catalyzed with N‐containing reagent, is successfully developed to synthesize P(VDF‐co‐TrFE‐co‐CTFE) containing unsaturation. The resultant polymer was carefully characterized with ¹H NMR, ¹⁹F NMR, and FTIR. The composition of the resultant copolymer is strongly influenced by reaction conditions, including the reaction temperature, catalyst concentration, the types of ligands and solvents. The kinetics data of the chain transfer and elimination reaction demonstrate their well‐controlled feature of the strategy. By shifting the equilibrium between the CTR and elimination reactions dominated by N‐compounds serving as ligands in SET‐CTR and catalyst in the dehydrochlorination of P(VDF‐co‐CTFE), P(VDF‐co‐TrFE‐co‐CTFE) with tunable TrFE and double‐bond content could be synthesized in this one‐pot route. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3429–3440     

Synthesis of Functionalized Vinylgermanes through a New Ruthenium‐Catalyzed Coupling Reaction

Vinyl‐substituted germanes react stereo‐ and regioselectively with olefins in the presence of complexes containing Ru? H and Ru? Ge bonds with the formation of functionalized vinylgermanes that cannot be synthesized by olefin cross‐metathesis procedures. The reaction opens a new catalytic route for preparation of a class of organogermanes that are potent organometallic reagents for organic synthesis because they show very low toxicity and could replace organotin compounds. The mechanism of this new catalytic route was proven to involve an interesting insertion of the vinylgermane into the Ru? H bond and β‐Ge transfer to the metal with elimination of ethylene and generation of an Ru? Ge bond, followed by insertion of the alkene into the Ru? Ge bond and β‐H transfer to the metal to eliminate the substituted vinylgermane.     

Asymmetric Hydrocyanation of Alkenes without HCN

A general and efficient rhodium‐catalyzed asymmetric cyanide‐free hydrocyanation of alkenes has been developed. Based on the asymmetric hydroformylation/condensation/aza‐Cope elimination sequences, a broad scope of substrates including mono‐substituted, 1,2‐, and 1,1‐disubstituted alkenes (involving natural product R‐ and S‐limonene) were employed, and a series of valuable chiral nitriles are prepared with high yields (up to 95 %) and enantioselectivities (up to 98 % ee). Notably, the critical factor to achieve high enantioseletivies is the addition of catalytic amount of benzoic acid. This novel methodology provides an efficient and concise synthetic route to the intermediate of vildagliptin and anagliptin.     

Halogenation of Fluorinated 1,3,5‐Triketones

The behavior of linear and cyclic fluorinated 1,3,5‐triketones and their metal derivatives towards common halogenating agents was examined, and optimal reaction conditions for the straightforward synthesis of mono‐, di‐, and tetrahalogenated products were found (Schemes 1–3). An aromatization through a double HBr elimination from an α,α′‐dibrominated cyclohexanone was shown to be a promising synthetic route to 1,1′‐(2‐hydroxy‐1,3‐phenylene)bis[2,2,2‐trifluoroethanones] (= 2,6‐bis(trifluoroacetyl)phenols; Scheme 4). Additionally, the 1,3,5‐triketones prepared add readily H₂O or alcohols to produce novel bridged 2,6‐dihydroxypyran‐4‐ones (Scheme 2). The structure of the obtained compounds 6a and 7a was confirmed by X‐ray structure analysis.     

The tert-butyl-NNO-azoxy group in the synthesis of 1,2,4-benzotriazin-3(4H)-one 1-oxides

Treatment of 2-(tert-butyl-NNO-azoxy)anilines with phosgene at 20 °C was proposed as a novel route to 1,2,4-benzotriazin-3(4H )-one 1-oxides. This method involves a new reaction, viz., an intramolecular interaction of the tert-butyl-NNO-azoxy group with a C-electrophile (leading to the formation of the N(2)—C(3) bond of the triazine ring) followed by elimination of the tert-butyl group. Complete assignment of the signals in the ¹H and ¹³C NMR spectra of the compounds obtained was performed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1507–1509, August, 2007.     

The reaction of 2-acetoacetamidopyridines with phosgene. A route to novel 3-Acetyl-2-chloro-4H-pyrido[ 1,2-a] pyrimidin-4-ones

2-(Acetoacetamido)pyridine, 1 , and its 5-methyl derivative, 2 , with phosgene, gave 3-acetyl-2-chloro-4H-pyrido[1,2-a]pyrimidin- 4 -one, 5 , and 3-acetyl-2-chloro-7-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one, 6 , respectively. The structures of these compounds followed from their elemental analyses, and interpretations of their uv, ir, pmr, and X-ray spectra. An alternative route to 5 and 6 , which sought first to react 1 and 2 with methyl - and benzyl chloroformates, was unsuccessful, and led, instead, to elimination of the acetoacetyl group with concomitant formation of the carbamate derivatives, 10 and 11 .     

An improvement of the canonicalP-V path elimination for recognizing Kekuléan benzenoid systems

The canonicalP-V path elimination for recognizing Kekuléan benzenoid systems has been given in ref. [1]. In this paper, we give a new definition of a canonicalP-V path of a benzenoid system which is an improvement of the definition in ref. [1], so that the canonicalP-V paths can be more easily recognized. By the new definition, we give an improved canonicalP-V path elimination.This project was supported by NSFC.     

Facile preparation of bis(thiocarbonyl)disulfides via elimination

A robust facile synthetic preparation of bis(thiocarbonyl)disulfides is presented. The route follows an elimination mechanism rather than the more common oxidation. Addition of p-tosyl chloride to a thiocarbonyl thiolate results in the elimination of the chloride by the trithiocarbonate anion and subsequent elimination of the tosyl leaving group (by a second thiocarbonyl thiolate). The side products of the reaction are bis(4-methylphenyl)disulfone and tosylate salts/acids.     

Synthesis of the bicyclo[7.3.0]dodecatrienediyne core of the C-1027 chromophore

[reaction: see text] C-1027, an extremely potent antitumor agent, is composed of chromophore 1 and an apoprotein. Here we report a general and efficient route to the exceedingly reactive bicyclo[7.3.0]dodecatrienediyne core of 1, utilizing selenoxide elimination and epoxide deoxygenation to build the cyclopentadiene and enediyne structures, respectively.     

Umamidierungsreaktionen an cyclischen Amino-amid-Systemen. 3. Mitteilung über Umamidierungsreaktionen

Transamidation Reactions with Cyclic Amino-amides Lactames which are substituted at the nitrogen atom by a 3-aminopropyl residue are transformed under base catalysis to cyclic amino-amides enlarged by 4 ring atoms. The formed ring must be at minimum 12-membered. Scheme 2 illustrates this result: the 8-membered 7 is transamidated in 96% yield to the 12-membered ring 8 (in the presence of potassium 3-aminopropylamid in 1, 3-propanediamine), the 9-membered 10 to the 13-membered ring 11 (97%) and the 11-membered 14 to the 15-membered ring 15 . Furthermore, the 13-membered ring 27 (Scheme 5) is transformed to the 17-membered 28 . In the case of the 15-membered lactame 15 it is demonstrated that 14 is not formed back under the conditions of the transamidation. Large ring lactames which are substituted at the nitrogen atom by a 3-(alkylamino) propyl group lead under base catalysis to an equilibrium mixture, e.g. the 17-membered 26 is in equilibrium with the 21-membered 29 . This result is similar to the behavior of the corresponding open-chain amino-amides [2]. Because of transannular interactions, the 11-membered ring 2 is not stable: transamidation of the 7-membered 1 (Scheme 1) doesn't give the expected 2 , but its water elimination product 3 in small yield. The N-tosyl derivative of 2 , namely 20 , is synthesized by an independent route (Scheme 3). Detosylation of 20 yields the 7-membered 1 instead of 2 . Concerning the mechanism of this interesting reaction see Scheme 4.