Terminal alkynes bonds

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

Terminal alkynes are only reduced in the presence of proton donors, e.g. ammonium sulfate, because the acetylide anion does not take up further electrons. If, however, an internal C—C triple bond is to be hydrogenated without any reduction of terminal, it is advisable to add sodium amide to the alkyne solution Hrst. On catalytic hydrogenation the less hindered triple bonds are reduced first (N.A. Dobson, 1955, 1961). 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

Many examples of insertions of internal alkynes are known. Internal alkynes react with aryl halides in the presence of formate to afford the trisubstituted alkenes[271,272]. In the reaction of the terminal alkyne 388 with two molecules of iodobenzene. the first step is the formation of the phenylacetylene 389. Then the internal alkyne bond, thus produced, inserts into the phenyl-Pd bond to give 390. Finally, hydrogenolysis with formic acid yields the trisubstituted alkene 391(273,274], This sequence of reactions is a good preparative method for trisubstituted alkenes from terminal alkynes. 

The benzene derivative 409 is synthesized by the Pd-catalyzed reaction of the haloenyne 407 with alkynes. The intramolecular insertion of the internal alkyne, followed by the intermolecular coupling of the terminal alkyne using Pd(OAc)2, Ph3P, and Cul, affords the dienyne system 408, which cyclizes to the aromatic ring 409[281]. A similar cyclization of 410 with the terminal alkyne 411 to form benzene derivatives 412 and 413 without using Cul is explained by the successive intermolecular and intramolecuar insertions of the two triple bonds and the double bond[282]. The angularly bisannulated benzene derivative 415 is formed in one step by a totally intramolecular version of polycycli-zation of bromoenediyne 414[283,284],... 

Among several propargylic derivatives, the propargylic carbonates 3 were found to be the most reactive and they have been used most extensively because of their high reactivity[2,2a]. The allenylpalladium methoxide 4, formed as an intermediate in catalytic reactions of the methyl propargylic carbonate 3, undergoes two types of transformations. One is substitution of cr-bonded Pd. which proceeds by either insertion or transmetallation. The insertion of an alkene, for example, into the Pd—C cr-bond and elimination of/i-hydrogen affords the allenyl compound 5 (1.2,4-triene). Alkene and CO insertions are typical. The substitution of Pd methoxide with hard carbon nucleophiles or terminal alkynes in the presence of Cul takes place via transmetallation to yield the allenyl compound 6. By these reactions, various allenyl derivatives can be prepared. 

The reaction of allyl halides with terminal alkynes by use of PdClifFhCNji as a catalyst affords the l-halo-l,4-pentadienes 297. 7r-AlIylpalladium is not an intermediate in this reaction. The reaction proceeds by chloropalladation of the triple bond by PdCh, followed by the insertion of the double bond of the allyl halide to generate 296. The last step is the regeneration by elimination of PdCh, which recycles[148]. The cis addition of allyl chloride to alkynes is supported by formation of the cyclopentenone 299 from the addition product 298 by Ni(CO)4-catalyzed carbonylation[149]. 

Hydrocarbons that contain a carbon-carbon triple bond are called alkynes Non cyclic alkynes have the molecular formula C H2 -2 Acetylene (HC=CH) is the simplest alkyne We call compounds that have their triple bond at the end of a carbon chain (RC=CH) monosubstituted or terminal alkynes Disubstituted alkynes (RC=CR ) have internal triple bonds You will see m this chapter that a carbon-carbon triple bond is a functional group reacting with many of the same reagents that react with the double bonds of alkenes... 

Anions of acetylene and terminal alkynes are nucleophilic and react with methyl and primary alkyl halides to form carbon-carbon bonds by nucleophilic substitution Some useful applications of this reaction will be discussed m the following section... 

Terminal alkyne (Section 9 1) AlkyneofthetypeRC=CH in which the tnple bond appears at the end of the chain... 

Terminal alkynes with no electron-withdrawing group next to the acetylenic linkage when treated with enamines merely add across the double bonds of the enamines (9i). But electrophilic alkynes (those with an electron-withdrawing group next to the acetylenic linkage) undergo cycloaddition reactions with enamines. 

Acetylene and terminal alkynes are CH-acidic compounds the proton at the carbon-carbon triple bond can be abstracted by a suitable base. Such a deprotonation is the initial step of the Glaser reaction as well as the Eglinton... 

The Pauson-Khand reaction was originally developed using strained cyclic alkenes, and gives good yields with such substrates. Alkenes with sterically demanding substituents and acyclic as well as unstrained cyclic alkenes often are less suitable substrates. An exception to this is ethylene, which reacts well. Acetylene as well as simple terminal alkynes and aryl acetylenes can be used as triple-bond component. 

Alkynes, like alkenes, can be cleaved by reaction with powerful oxidizing agents such as ozone or KMnC, although the reaction is of little value and we mention it only for completeness. A triple bond is generally less reactive than a double bond and yields of cleavage products are sometimes low. The products obtained from cleavage of an internal alkyne are carboxylic acids from a terminal alkyne, CO2 is formed as one product. 

Strategy Compare the product with the starting material, and catalog the differences. In this case, we need to add three carbons to the chain and reduce the triple bond. Since the starling material is a terminal alkyne that can be alkylated, we might first prepare the acetylide anion ol 1-pentyne, let it react with 1-bromopropane, and then reduce the product using catalytic hydrogenation. 

Alkynes show a C=C stretching absorption at 2100 to 2260 cm i, an absorption that is much more intense for terminal alkynes than for internal alkynes. In fact symmetrically substituted triple bonds like that in 3-hexyne show no absorption at all, lor reasons we won t go into. Terminal alkynes such as 1-hexyne also have a characteristic =C-H stretch at 3300 cm-1 (Figure 12.14c). This band is diagnostic for terminal alkynes because it is fairly intense and quite sharp. 

Problem 13.12 We saw in Section 8.3 that addition of HBr to a terminal alkyne leads to the Markovnikov addition product, with the Br bonding to the more highly substituted carbon. How could you use 13C NMR to identify the product of the addition of 1 equivalent of HBr to 1-hexyne ... 

A synthetically useful virtue of enol triflates is that they are amenable to palladium-catalyzed carbon-carbon bond-forming reactions under mild conditions. When a solution of enol triflate 21 and tetrakis(triphenylphosphine)palladium(o) in benzene is treated with a mixture of terminal alkyne 17, n-propylamine, and cuprous iodide,17 intermediate 22 is formed in 76-84% yield. Although a partial hydrogenation of the alkyne in 22 could conceivably secure the formation of the cis C1-C2 olefin, a chemoselective hydrobora-tion/protonation sequence was found to be a much more reliable and suitable alternative. Thus, sequential hydroboration of the alkyne 22 with dicyclohexylborane, protonolysis, oxidative workup, and hydrolysis of the oxabicyclo[2.2.2]octyl ester protecting group gives dienic carboxylic acid 15 in a yield of 86% from 22. 

Although beyond the scope of the present discussion, another key realization that has shaped the definition of click chemistry in recent years was that while olefins, through their selective oxidative functionalization, provide convenient access to reactive modules, the assembly of these energetic blocks into the final structures is best achieved through cydoaddition reactions involving carbon-het-eroatom bond formation, such as [l,3]-dipolar cydoadditions and hetero-Diels-Al-der reactions. The copper(i)-catalyzed cydoaddition of azides and terminal alkynes [5] is arguably the most powerful and reliable way to date to stitch a broad variety... 

The hydration of triple bonds is generally carried out with mercuric ion salts (often the sulfate or acetate) as catalysts. Mercuric oxide in the presence of an acid is also a common reagent. Since the addition follows Markovnikov s rule, only acetylene gives an aldehyde. All other triple-bond compounds give ketones (for a method of reversing the orientation for terminal alkynes, see 15-16). With allqmes of the form RC=CH methyl ketones are formed almost exclusively, but with RC=CR both possible products are usually obtained. The reaction can be conveniently carried out with a catalyst prepared by impregnating mercuric oxide onto Nafion-H (a superacidic perfluorinated resinsulfonic acid). ... 

Triple bonds can also be selectively reduced to double bonds with DIBAL-H, " with activated zinc (see 12-36), with hydrogen and Bi2B-borohydride exchange resin, ° or (internal triple bonds only) with alkali metals (Na, Li) in liquid ammonia or a low-molecular-weight amine.Terminal alkynes are not reduced by the Na—NH3 procedure because they are converted to acetylide ions under these conditions. However, terminal triple bonds can be reduced to double bonds by the... 

Triple bonds can be monohydroborated to give vinylic boranes, which can be reduced with carboxylic acids to cis alkenes or oxidized and hydrolyzed to aldehydes or ketones. Terminal alkynes give aldehydes by this method, in contrast to the mercuric or acid-catalyzed addition of water discussed at 15-4. However, terminal alkynes give vinylic boranes (and hence aldehydes) only when treated with a hindered borane such as 47, 48, or catecholborane (p. 798)," or with BHBr2—SMe2. The reaction between terminal alkynes and BH3 produces 1,1-... 

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