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.     

Tuning of regioselectivity in the coupling reaction involving allenic/propargylic palladium species

Two different types of coupling patterns for the Pd(0)-catalyzed coupling reaction of allenic/propargylic zinc reagents with organic halides or propargylic carbonates (acetate) with the corresponding organometallic reagents were observed. After studying the controlling factors on the regioselectivity of this reaction, we demonstrated that the steric hindrance of both reactants and the types of organic halides determine the regioselectivity of this coupling reaction. By subtle choosing of the substrates, the regioselectivity can be tuned. On the basis of these results, new methodologies for the highly regio- and stereoselective synthesis of 6-substituted hex-5-yn-2-enoates and 4,6-dialkylhexa-2,4,5-trienoates have been developed. Some of the products synthesized by the carbonate protocol cannot be prepared by the lithiation protocol because the regioselectivity of lithiation of dialkyl-substituted internal alkynes is an intrinsic problem.     

Coupling reactions of aryl bromides with 1-alkynols catalysed by a tetraphosphine/palladium catalyst

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ system catalyses efficiently the coupling reactions of aryl halides with a variety of alkynols such as propargyl alcohol, but-1-yn-4-ol, pent-1-yn-5-ol or hex-1-yn-6-ol. The catalyst can be used at low loading. Higher reaction rates were observed in the presence of but-1-yn-4-ol, pent-1-yn-5-ol or hex-1-yn-6-ol than with propargyl alcohol. The protection of the alcohol functions as an ether or a silyloxy group led generally to similar or better results than the reactions performed with the unprotected alcohols.     

The co-cyclotrimerization of hexynes and phenylacetylene with niobium(V) chloride as catalyst

Various alkynes were cyclotrimerized with NbCl₅ as catalyst and C₂H₅AlCl₂ as co-catalyst at an Al/Nb molar ratio = 2 in CCl₄ at room temperature and pressure. The tendency of the alkynes to cyclotrimerize decreased in the following order: phenylacetylene > hex-1-yne > hex-2-yne ~ hex-3-yne ~ oct-4-yne If phenylacetylene (X) was co-cyclotrimerized with another alkyne (Y), four different cyclotrimers were found, as represented by the following equation: X + Y → X₃ + X₂Y + XY₂ + Y₃ If the amount of cyclotrimers formed is plotted against the phenylacetylene mole fraction, a statistically random distribution of the products is observed. Differences with regard to the ideal random case are attributed to a polymerization reaction. During the cyclo-trimerization process there is therefore a statistically random coordination of the alkynes on the catalytic species, after which ring closure occurs to form the cyclotrimeric products.     

Synthesis of [3-(trimethylsilyl)prop-2-yn-1-yl] selenides

Efficient and selective methods have been developed for the synthesis of previously unknown organyl [3-(trimethylsilyl)prop-2-yn-1-yl] selenides, organyl prop-2-yn-1-yl selenides, and bis[3-(trimethylsilyl) prop-2-yn-1-yl] selenide by reactions of 3-bromo-1-(trimethylsilyl)prop-1-yne with the corresponding organylselenolates and sodium selenide generated from diorganyl diselenides or elemental selenium by the action of sodium tetrahydridoborate.     

An ab initio/RRKM study of product branching ratios in the photodissociation of buta-1,2- and -1,3-dienes and but-2-yne at 193 nm

Ab initio G2M(MP2)//B3LYP/6-311G** calculations have been performed to investigate the reaction mechanism of photodissociation of buta-1,2- and -1,3-dienes and but-2-yne after their internal conversion into the vibrationally hot ground electronic state. The detailed study of the potential-energy surface was followed by microcanonical RRKM calculations of energy-dependent rate constants for individual reaction steps (at 193 nm photoexcitation and under collision-free conditions) and by solution of kinetic equations aimed at predicting the product branching ratios. For buta-1,2-diene, the major dissociation channels are found to be the single Cbond;C bond cleavage to form the methyl and propargyl radicals and loss of hydrogen atoms from various positions to produce the but-2-yn-1-yl (p1), buta-1,2-dien-4-yl (p2), and but-1-yn-3-yl (p3) isomers of C(4)H(5). The calculated branching ratio of the CH(3) + C(3)H(3)/C(4)H(5) + H products, 87.9:5.9, is in a good agreement with the recent experimental value of 96:4 (ref. 21) taking into account that a significant amount of the C(4)H(5) product undergoes secondary dissociation to C(4)H(4) + H. The isomerization of buta-1,2-diene to buta-1,3-diene or but-2-yne appears to be slower than its one-step decomposition and plays only a minor role. On the other hand, the buta-1,3-diene-->buta-1,2-diene, buta-1,3-diene-->but-2-yne, and buta-1,3-diene-->cyclobutene rearrangements are significant in the dissociation of buta-1,3-diene, which is shown to be a more complex process. The major reaction products are still CH(3) + C(3)H(3), formed after the isomerization of buta-1,3-diene to buta-1,2-diene, but the contribution of the other radical channels, C(4)H(5) + H and C(2)H(3) + C(2)H(3), as well as two molecular channels, C(2)H(2) + C(2)H(4) and C(4)H(4) + H(2), significantly increases. The overall calculated C(4)H(5) + H/CH(3) + C(3)H(3)/C(2)H(3) + C(2)H(3)/C(4)H(4) + H(2)/C(2)H(2) + C(2)H(4) branching ratio is 24.0:49.6:4.6:6.1:15.2, which agrees with the experimental value of 20:50:8:2:2022 within 5 % margins. For but-2-yne, the one-step decomposition pathways, which include mostly H atom loss to produce p1 and, to a minor extent, molecular hydrogen elimination to yield methylethynylcarbene, play an approximately even role with that of the channels that involve the isomerization of but-2-yne to buta-1,2- or -1,3-dienes. p1 + H are the most important reaction products, with a branching ratio of 56.6 %, followed by CH(3) + C(3)H(3) (23.8 %). The overall C(4)H(5) + H/CH(3) + C(3)H(3)/C(2)H(3) + C(2)H(3)/C(4)H(4) + H(2)/C(2)H(2) + C(2)H(4) branching ratio is predicted as 62.0:23.8:2.5:5.7:5.6. Contrary to buta-1,2- and -1,3-dienes, photodissociation of but-2-yne is expected to produce more hydrogen atoms than methyl radicals. The isomerization mechanisms between various isomers of the C(4)H(6) molecule including buta-1,2- and -1,3-dienes, but-2-yne, 1-methylcyclopropene, dimethylvinylidene, and cyclobutene have been also characterized in detail.     

Haloacetylated enol ethers: 18 : Synthesis of alkyl 6-[azol-3(5)-yl]hexanoates

A convenient method for the synthesis of eight alkyl 6-[4,5-dihydroisoxazol-3-yl(-pyrazol-3(5)-yl)]hexanoates from the cyclocondensation of methyl 10,10,10-trifluoro[chloro]-9-oxo-7-methoxydec-7-enoates and hydroxylamine hydrochloride or hydrazine hydrochloride, respectively, in ethanol as solvent is reported. The reaction of methyl 10,10,10-trichloro-9-oxo-7-methoxydec-7-enoates with hydrazines furnished the pyrazole derivatives with the simultaneous transformation of trichloromethyl to carboxyl group.     

Convenient and efficient stereoselective synthesis of (2Z)-2-(chloromethyl)alk-2-enoates using iron(III) or indium(III) chloride

The stereoselective synthesis of (2Z)-2-(chloromethyl)alk-2-enoates has been achieved efficiently and in high yields and in short reaction times from Baylis-Hillman adducts, 3-hydroxy-2-methylene-alkanoates, by treatment with FeCl₃ or InCl₃ at room temperature.     

Synthesis of pyrazoles and oxyquinoxalines from 2,4-dioxohexenoales

Condensation of ethyl 2,4-dioxo-6-phenylhex-5-enoates (I; R = H, I; R = Me, I, R = Ph) with various hydrazines yielded ethyl 5-styrylpyrazole-3-carboxylates (III), which were hydrolyzed to the acids (IV), and ozonized to 5-keto pyrazole esters (VI) and acids (VII). Reduction of the 5-formylpyrazoles (VI; R = II) with borohydride afforded the 5-hydroxymethyl derivatives (VIII). The same 2,4-dioxohexenoates (I) when treated with o-phenylenediamine gave 2-oxy-quinoxalines (V; R = H, V; R = Me, V; R = Ph). The uv spectra data of these compounds are given.     

trans-RhCl(CO)(PPh3)2-catalyzed monomeric and dimeric cycloisomerization of propargylic 2,3-dienoates. Establishment of alpha,beta-unsaturated delta-lactone rings by cyclometallation

Cyclometallation of two unsaturated carbon-carbon bonds usually requires the application of low-valent metal catalysts, which could cleave the propargylic ester linkage. Thus, it is desirable to identify a catalyst which could undergo cyclometallation without cleaving the propargylic ester linkage. In this paper, we used trans-RhCl(CO)(PPh(3))(2) to realize the cyclometallation of propargylic 2,3-dienoates. The substituents at the 4-position of allenoate moiety nicely control the reaction pathway: when the 4-position of propargylic 2,3-dienoate 1 was monosubstituted with an aryl group, the bicyclic intermediate 7 formed by the cyclometallation could highly selectively undergo carbometalation with the alkyne moiety in the second molecule of propargylic 2,3-dienoate 1 to afford metallabicyclic intermediates 8a or 8b. Subsequent reductive elimination would afford 9, which could undergo an intramolecular Diels-Alder reaction resulting in the formation of polycyclic bis(delta-lactone)-containing structures 2. The intermediate could be trapped by adding 3-methoxyprop-1-yne affording cyclization-aromatization product 4p highly selectively. If the substituent at the 4-positon of the 2,3-allenoate moiety has a beta-H atom, sequential unimolecular cyclometallation/beta-H elimination/reductive elimination occurs to afford cross-conjugated 5(Z)-alkylidene-4-alkenyl-5,6-dihydropyran-2-ones. The Z-stereochemistry of the exo double bond was determined by the cyclometallation. Some of the alpha,beta-unsaturated delta-lactones could be easily converted to other synthetically useful compounds via reduction reaction, hydrogenation, and iodination/coupling protocol.     

(E)-1-氯-6,6-二甲基-2-庚烯-4-炔的立体选择性合成

(E)-1-氯-6,6-二甲基-2-庚烯-4-炔是合成盐酸特比萘芬的关键中间体,N-氯代二异丙胺/三苯基膦与6,6-二甲基-1-庚烯-4-炔-3-醇反应,可以立体选择性地得到反式的该化合物,其反式/顺式异构体的比例达9/1,为特比萘芬提供了可工业放大生产的立体选择性合成方法。     

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.     

Reactions of 1,1,4,4-tetramethylsemicarbazide with prop-2-ynyl bromide, allyl bromide, and 1,3-dibromoprop-1-yne

1,1,4,4-Tetramethylsemicarbazide readily undergoes alkylation with prop-2-ynyl bromide and allyl bromide at the tertiary nitrogen atom of the hydrazine fragment to give 1-(prop-2-yn-1-yl)-and 1-(prop-2-en-1-yl)-1,1-dimethyl-2-(dimethylaminocarbonyl)hydrazinium bromides, respectively. A new procedure was proposed for the synthesis of 6-bromomethylidene-2-dimethylamino-4,4-dimethyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-ium bromide by reaction of 1,1,4,4-tetramethylsemicarbazide with 1,3-dibromoprop-1-yne in acetonitrile.     

Enantioselective cyclization/hydrosilylation of 1,6-enynes catalyzed by a cationic rhodium bis(phosphine) complex

[reaction: see text] Reaction of 4,4-dicarbomethoxy-1-octene-6-yne (1) with triethylsilane and a catalytic 1:1 mixture of [Rh(COD)(2)](+) SbF(6)(-) and (R)-BIPHEMP (5 mol %) at 70 degrees C for 90 min gave (Z)-1,1-dicarbomethoxy-3-(1-triethylsilyl)ethylidene-4-methylcyclopentane (2) in 81% isolated yield with 98% de and 92% ee.     

嘌呤N-6-吡啶盐中间体的形成及其在嘌呤核苷合成上的应用

本文报道以次黄苷为原料, 经酯化, 再在缩合剂4-氯苯磷酰二氯存在下与吡啶反应, 形成嘌呤N-6-吡啶盐中间体2, 该中间体2分别与碱性强弱不同的胺或氨及2moldm^-^3NaOH的醇溶液在室温反应, 可方便的合成6-NH2, 6-OCH3以及6-OCH2CH3-9-(β-D-呋喃核糖)嘌呤衍生物。并对以上产物形成的机制作了探讨。     

Cyclization and rearrangement products from coupling reactions between terminal o-alkynylphenols or o-ethynyl(hydroxymethyl)benzene and 6-halopurines

Cyclization reactions on 6-[(2-hydroxyphenyl)ethynyl]purines, 6-[(2-hydroxymethylphenyl)ethynyl]purines and 6-[(2-hydroxyphenyl)propyn-1-yl]purines have been studied. 6-(2-Benzofuryl)purines are readily available via a one-pot Sonogashira coupling-cyclization between 6-iodopurine and 2-ethynylphenol. When the same reaction was performed with o-(hydroxymethyl)ethynylbenzene, 6-[isobenzofuran-1(3H)-ylidenemethyl]purine was formed, mainly as the (E)-isomer. Acid catalyzed isomerization of the (E)-compound afforded the (Z)-isomer. The latter compound was also formed from a two-step reaction; Sonogashira coupling with O-silylated alkyne followed by deprotection and subsequent 5-exo cyclization. Sonogashira coupling between 6-halopurines and 2-propynylphenol gave only the alkyne coupling product and no cyclization took place. However, the Sonogashira product was unexpectedly rearranged to 6-(3-phenoxypropa-1,2-dienyl)purines under basic conditions. Theoretical calculations demonstrated that the allenes are more stable than their alkyne isomers.     

(−)-Sparteine-Mediated Asymmetric Intramolecular Carbolithiation of Alkenes: Synthesis of Enantiopure Cyclopentanes with Three Consecutive Stereogenic Centers

An asymmetric intramolecular carbolithiation reaction was developed by combining the (−)-sparteine-mediated enantiotopos-differentiating deprotonation and the anionic 5-exo-trig cyclization. Achiral 6-phenylhex-5-enyl carbamates were efficiently cyclized furnishing regio-, diastereo- (dr >99 : 1), and enantioselectively (er >98 : 2) 1,2-trans-substituted cyclopentanes. The intermediate primary benzylic lithium-carbanion pairs were – in spite of their configurative lability – diastereoselectively substituted by versatile electrophiles creating a third consecutive stereogenic center. Additionally, some 4-functionalized 6-phenylhex-5-enyl carbamates were also cyclized in high yield to provide enantiomerically pure cyclopentanes incorporating three adjacent stereogenic centers.     

Regioselective synthesis of polyfluoroalkyl-substituted 7-(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-1-yl)-6,7-dihydro-1<Emphasis Type="Italic">H</Emphasis>-indazol-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

3-Polyfluoroalkyl-6,6-dimethyl-7-(1H-1,2,3-triazol-1-yl)-6,7-dihydro-1H-indazol-4(5H)-ones were synthesized with high regioselectivity by 1,3-dipolar cycloaddition of terminal alkynes (phenylacetylene, hex- 1-yne, hept-1-yne, and but-3-yn-1-ol) to 7-azido-6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol-4(5H)-ones which were prepared by bromination of 6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol- 4(5H)-ones with N-bromosuccinimide in anhydrous carbon tetrachloride, followed by treatment of the corresponding 7-bromo derivatives with sodium azide.     

Total Synthesis of 3 (R)-Panaxynol

Panaxynol1,asacommonconstituentofmanyplantparts',wasfirstdescribedbyTakahashietal.2in1964asaconstituentofPanaxyginseng.C.A.MeyershowedinhisBioassayshowedthatpanaxynolhadselectiveinvitrocytotoxicityagainstL-1210',MKI,B-16,andL-929cancercelllinescomparedtonormalcellcultures4.TheabsoluteconfigurationhadbeenestablishedbyLarsenetal.5tobe3R.Hereinwereportthefirsttotalstereoselectivesynthesisofpanaxynol(l).C'-CIafragmentofpanaxynol1wasobtainedaccordingtothefollowingsequencefReagentsandconditio…     

Synthesis of substituted quinolines by iron-catalyzed coupling reactions between chloroenynes and Grignard reagents

This letter reports the preparation of quinolines, substituted at the 2- or 3-position by a 4-substituted but-3-en-1-yne group, by the environmentally friendly iron(III)-catalyzed coupling reaction of Grignard reagents with 1-chloro-4-(2-quinolyl)but-1-en-3-yne. The extension and the scope of this non-toxic and chemoselective procedure to various functionalized unsaturated vinyl chlorides are described.