Efficient synthesis of enynes by tetraphosphine-palladium-catalysed reaction of vinyl bromides with terminal alkynes

Through the use of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as catalyst, a range of vinyl bromides undergoes Sonogashira cross-coupling reaction with a variety of alkynes, leading to the corresponding 1,3-enynes in good yields. The reaction tolerates several alkynes such as phenylacetylene, dec-1-yne, 2-methylbut-1-en-3-yne a range of alk-1-ynols, 3,3-diethoxyprop-1-yne and a propargyl amine. Higher reactions rates were observed in the presence of phenylacetylene, dec-1-yne, but-3-yn-1-ol, pent-4-yn-1-ol, 3,3-diethoxyprop-1-yne or 1,1-dipropyl-2-propynylamine than with propargyl alcohol, 3-methoxy-prop-1-yne or 2-methylbut-1-en-3-yne. This catalyst can be used at low loading even for reactions of sterically hindered vinyl bromides such as bromotriphenylethylene or 2-bromo-3-methyl-but-2-ene.     

Synthesis of 1,5-diphenylpent-3-en-1-yne derivatives utilizing an aqueous B-alkyl Suzuki cross coupling reaction

1,5-Diphenylpent-3-en-1-yne derivatives were isolated in minor quantities from terrestrial plants and exhibited strong anti-inflammatory activity. A cross coupling reaction between B-benzyl-9-BBN and chloroenynes under mild condition was developed resulting in the formation of different 1,5-diphenylpent-3-en-1-yne derivatives with a full control on the E/Z selectivity. Several substrates bearing electron-donating and electron-withdrawing substituents were tolerable under the reaction conditions affording the corresponding products in good yields. This is the first study to report the synthesis of a vast array of novel 1,5-diphenylpent-3-en-1-yne derivatives paving the way for the preparation of tailored derivatives on mass scale necessary for biological studies and drug development.     

Synthesis and structure of 1-metallacyclopent-3-yne complexes of group 4 metals

Five-membered metallacyclic alkyne complexes of titanium and hafnium, 1,1-bis(cyclopentadienyl)-1-titanacyclopent-3-yne (2) and trans-1,1-bis(cyclopentadienyl)-2,5-trimethylsilyl-1-hafnacyclopent-3-yne (6), were synthesized and structurally characterized. The structural analysis of titanium complex 2 implied a larger contribution of an η⁴-π,π-coordinated structure. The hafnium compound 6 has a similar structure to the corresponding zirconium analogue (1a), although slight differences in the bond lengths and angles were observed. A novel 1-zirconacyclopent-3-yne complex, 1,1-bis(methylcyclopentadienyl)-2,5-bis(trimethylsilyl)-1-zirconacyclopent-3-yne (5), was also prepared and the structure of the trans-isomer was determined.     

Kinetics of the reaction of <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylaniline with 1-bromoalk-2-ynes

Quaternization of N,N-dimethylaniline with propargyl bromide, 1-bromobut-2-yne, and 1-bromooct-2-yne were studied. It was shown that, with the lengthening chain of the substituent at the triple bond, the quaternization rate tends to increase.     

N,N′,N″-1,4,7-Triazacyclononane with pendant alkyne arms: Crystal structures of [CuL2′][PF6]2, [NiL2′][ClO4]2 and CuL″Cl2 (L′=N-(4-but-2-yne)-1,4,7-triazacyclononane,L″=N-(5-pent-2-yne)-1,4,7-triazacyclononane)

We report the synthesis of a series of macrocyclic ligands based on N,N′,N″-1,4,7-triazacyclononane with pendant alkyne arms. N,N′,N″-tris-(3-prop-1-yne)-1,4,7-triazacyclononane (L) has three pendant alkyne arms while N-(4-but-2-yne)1,4,7-triazacyclononane (L′) and N-(5-pent-2-yne)-1,4,7-triazacyclononane (L″) each have a single pendant arm. The ligands form coordination complexes with Cu(II), Ni(II), Co(II) and Mo(0). The crystal structures of [CuL₂′][PF₆]₂, [NiL₂′][ClO₄]₂ and CuL″Cl₂ are presented and discussed.     

Tetracationic compounds based on 1,4-diazabicyclo[2.2.2]octane: antibacterial activity and reactions with N-containing nucleophiles

Antibacterial activity of tetracationic compounds based on 1,4-diazabicyclo[2.2.2]octane (DABCO) bis-quaternary salts with dodecyl substituents bound by linker groups containing four carbon atoms was studied. All the compounds exhibited activity against the test-strains under study. The gram-positive culture S. aureus was found to be the most sensitive to the influence of compounds in question. The highest activity against S. aureus was exhibited by the compounds containing a but-2-yne or a butane linker; their efficiency exceeded that of the reference compound, antibiotic Ciprofloxacin. For the gram-negative culture P. aeruginosa, the highest activity was exhibited by the compound containing a but-2-yne linker. The compounds with a but-2-yne or a butane linker are stable in the presence of nitrogen-containing nucleophiles, which makes them promising for further studies.     

Improved synthesis of (9Z)-9,13-tetradecadien-11-ynal, the sex pheromone of the avocado seed moth, Stenoma catenifer

The terminal dienyne of (9Z)-9,13-tetradecadien-11-ynal, the sex pheromone of the avocado seed moth, Stenoma catenifer, was constructed by coupling a vinyl iodide precursor with commercially available 1-buten-3-yne with Pd catalysis, resulting in a short and efficient synthesis of the pheromone.     

Reactivite des dienes fonctionnels—VIII: Addition du tetracyanoethylene sur les dienes conjugues lineaires

Functional conjugated dienes undergo 1,4-cycloaddition with tetracyanoethylene to give cyclohexenes. With the Z isomers of 1-ethylthiobutadienes, an ethylenic cyclobutane, rapidly turning into cyclohexene, is detected. Stereochemistry and kinetic study indicate a two-step ionic process. The l-methoxy-l-butene-3-yne Z gives an ethylenic cyclobutene which is converted in a conjugated triene by an electrocyclic opening.     

Studies into diastereoselective Dötz benzannulations for the synthesis of axially chiral biaryls

A series of racemic chiral ortho substituents on 1-phenylhex-1-yne have been found to control the atroposelective formation of a biaryl from Dötz benzannulation with pentacarbonyl(methoxyphenylmethylene)chromium(0). The results show there is a subtle balance between the chiral ortho substituent controlling atroposelectivity with a dr 3-5:1 and allowing benzannulation to proceed in yields of 44-67%.     

New stereoselective methodology for the synthesis of dihydroxerulin and xerulin, potent inhibitors of the biosynthesis of cholesterol

A new stereoselective methodology for the synthesis of both dihydroxerulin and xerulin has been devised. The key step required cross-coupling reactions between the bromo trienyne, (1E,3E,5E)-1-bromo-8-trimethylsilyl-1,3,5-octatrien-7-yne and the appropriate conjugated diynes. The palladium-catalyzed tandem cross-coupling/cyclization reaction of the resulting polyenynes with (Z)-3-iodo-2-propenoic acid led directly to dihydroxerulin or xerulin with a high degree of stereoselectivity.     

Studies on the mechanism for stereoisomerization of 1-zirconacyclopent-3-yne compounds

The stereoisomerization of 2,5-disubstituted 1-zirconacyclopent-3-yne compounds, stable five-membered cycloalkynes, has been studied with regard to the mechanism. The bimetallic complex of 1,4-bis(trimethylsilyl)butatriene was synthesized and structurally characterized, although it seems unimportant for the stereoisomerization reactions. The isomerization of trans-1,1-bis(η⁵-cyclopentadienyl)-2,5-bis(trimethylsilyl)-1-zirconacyclopent-3-yne 2a into the cis-form in benzene-d₆ solution were observed using ¹H NMR spectroscopy at 50 °C in various concentrations. The reaction was first order with respect to trans-2a. This ruled out the possibility that a bimetallic complex was responsible for the isomerization. A kinetic isotope effect was observed (k_H/k_D = 1.8), suggesting that C–H activation is involved in the rate-determining step. A mechanism via hydrogen elimination from the complex of η⁴-π,π-coordination mode is proposed.     

The synthesis,structure and reactions of the novel cationic bisbut-2-yne complex [W(CO)(NCMe)(S2CNC4H8)(η2-MeC2Me)2][BPh4]

The complex [WI(CO)(S₂CNC₄H₈)(η²-MeC₂Me)₂] reacts with an equimolar amount of Na[BPh₄] in acetonitrile at room temperature to give the cationic bisbut-2-yne complex [W(CO)(NCMe)(S₂CNC₄H₈)(η²-MeC₂Me)₂][BPh₄] (1) by replacement of an iodide ligand by acetonitrile. The crystal structure of 1 has been determined and reveals a pseudo-octahedral geometry with the mid points of the two cis-but-2-yne ligands approximately coplanar with the sulphur atoms of the dithiocarbamate ligand. Carbon monoxide and acetonitrile occupy the axial sites. ¹³C NMR spectroscopy shows the two but-2-yne ligands in 1 donate a total of 6 electrons to the tungsten. Preliminary studies of the chemistry of 1 are also described.     

Research on African medicinal plants—II: Hypoxoside,a new glycoside of uncommon structure from hypoxis obtusa busch

A new glycoside, hypoxoside, was isolated from rhizome of Hypoxis obtusa, a plant used in Mozambique in native medicine for the treatment of urinary diseases. The structure 1 of a diglycoside of 1-(3′,4′-dihydroxyphenyl)-5-(3″,4″-dihydroxyphenyl)-1-penten-4-yne was attributed to hypoxoside on the basis of physico-chemical determinations and chemical behaviour.     

Studies on the mechanism for stereoisomerization of 1-zirconacyclopent-3-yne compounds

The stereoisomerization of 2,5-disubstituted 1-zirconacyclopent-3-yne compounds, stable five-membered cycloalkynes, has been studied with regard to the mechanism. The bimetallic complex of 1,4-bis(trimethylsilyl)butatriene was synthesized and structurally characterized, although it seems unimportant for the stereoisomerization reactions. The isomerization of trans-1,1-bis(η⁵-cyclopentadienyl)-2,5-bis(trimethylsilyl)-1-zirconacyclopent-3-yne 2a into the cis-form in benzene-d₆ solution were observed using ¹H NMR spectroscopy at 50 °C in various concentrations. The reaction was first order with respect to trans-2a. This ruled out the possibility that a bimetallic complex was responsible for the isomerization. A kinetic isotope effect was observed (k_H/k_D = 1.8), suggesting that C–H activation is involved in the rate-determining step. A mechanism via hydrogen elimination from the complex of η⁴-π,π-coordination mode is proposed.     

Reaction of 1,4-pentadiyne with diethylaminotrimethylstannane

The reaction between 1,4-pentadiyne and diethylaminotrimethylstannane leads predominantly to (E)-2-diethylamino-4-trimethylstannyl-2,4-pentaenyne (with either a 1/1 or 1/2 mol ratio of 1,4-pentadiyne and diethylaminotrimethylstannane). With 1/2 stoicheiometry 1,1,5-tris(trimethylstannyl)penta-1,2-dien-4-yne is formed as a minor product. ¹³C and ¹¹⁹Sn NMR data are reported.     

Cyclotrimerization of alkynes catalyzed by the naphthalene ruthenium complex [CpRu(C10H8)]+

The naphthalene ruthenium complex [CpRu(C₁₀H₈)]⁺ (in the presence of Cl^? ions) catalyzes the cyclotrimerization of 2,2-dimethyl-5,5-dipropargyl-1,3-dioxane-4,6-dione with alkynes (acetylene, hex-1-yne, hex-3-yne, oct-1-yne, phenylacetylene, trimetylsilylacetylene, octa-1,7-diyne, pent-1-yn-5-ol, methyl propargyl ether, and propargyl acetate) giving tricyclic aromatic compounds in 55–85% yields.     

Generation of bis(pentafluorophenyl)borane-dimethyl sulfide complex as a solution of hexane and its application to hydroboration of alk-1-yne with pinacolborane

A solution of bis(pentafluorophenyl)borane-dimethyl sulfide complex in hexane was generated by redistribution between tris(pentafluorophenyl)borane and borane-dimethyl sulfide complex. In the resulting solution a stoichiometric hydroboration of alk-1-yne with pinacolborane proceeded well at room temperature to afford (E)-alk-1-enylboronic acid pinacol ester in high yield. Bis(pentafluorophenyl)borane-dimethyl sulfide complex served as a mediator for the hydroboration.     

Total synthesis of two naturally occurring polyacetylenic glucosides (−)-bidensyneoside A1 and B,and an analogue of (−)-bidensyneoside C

The total syntheses of two novel polyacetylenic natural products bidensyneoside A1 and B, as well as an analogue of bidensyneoside C are described. These syntheses are based on our recently developed strategy. A new preparation of the required starting material (E)-3-penten-1-yne was developed. The preparation of the analogue of (−)-bidensyneoside C further confirms the side chain configuration of the natural product as (R).     

Domino reaction of 2,3-dichloroprop-1-ene with diphenyl disulfide in the system hydrazine hydrate-potassium hydroxide

2,3-Dichloroprop-1-ene reacted with diphenyl disulfide in the system hydrazine hydrate-potassium hydroxide at 30–35°C to give three products: 2-chloro-3-phenylsulfanylprop-1-ene, 1-phenylsulfanylpropadiene, and 1-phenylsulfanylprop-1-yne. Variation of temperature ensures selective synthesis of one of the above products, which confirms their successive formation (domino reaction). The domino reaction at 60°C goes further to afford (Z)-1,2-bis(phenylsulfanyl)prop-1-ene.     

Preparation and reactivity of macrocyclic dienynes

(1E,5E)-Cyclopentadeca-1,5-dien-3-yne (1c), which represents the first macrocyclic 1,5-dien-3-yne, can be obtained by thermal- or butyllithium-induced fragmentation of the corresponding 1,2,3-selenadiazole 8. The (E,E)-dienyne functionality causes a geometrical strain E_g, which enhances the reactivity in addition (1c→12,13) and cycloaddition (1c→10) reactions and lowers the isomerization barrier to the unstrained (E,Z)-configuration 1d (E_g = 0). A slow process 1c→1d occurs even at ambient temperatures within several weeks.