Hydrogen bonding terminal alkynes

Oxidation of organoboranes to alcohols is usually effected with alkaline hydrogen peroxide. The reaction is of wide applicability and many functional groups are unaffected by the reaction conditions, so that a variety of substituted alkenes can be converted into alcohols by this procedure. Several examples have been given above. A valuable feature of the reaction is that it results in the overall addition of water to the double (or triple) bond, with a regioselectivity opposite to that from acid-catalysed hydration. This follows from the fact that, in the hydroboration step, the boron atom adds to the less-substituted carbon atom of the multiple bond. Terminal alkynes, for example, give aldehydes in contrast to the methyl ketones obtained by mercury-assisted hydration. 

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). 

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. 

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. 

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. 

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... 

Some hydrometalation reactions have been shown to be catalyzed by zirconocene. For instance, CpiZrCf-catalyzed hydroaluminations of alkenes [238] and alkynes [239] with BU3AI have been observed (Scheme 8-34). With alkyl-substituted internal alkynes the process is complicated by double bond migration, and with terminal alkynes double hydrometalation is observed. The reaction with "PrjAl and Cp2ZrCl2 gives simultaneously hydrometalation and C-H activation. Cp2ZrCl2/ BuIi-cat-alyzed hydrosilation of acyclic alkenes [64, 240] was also reported to involve hydrogen transfer via hydrozirconation. 

In an effort to apply the cooperative principles of metalloenzyme reactivity, involving a combination of metal-ligand and hydrogen bonding, we have reported a ruthenium catalyst incorporating imidazolyl phosphine ligands that efficiently and selectively hydrates terminal alkynes (5). We subsequently found that application of pyridyl phosphines to the reaction resulted in a >10-fold rate enhancement and complete anti-Markovnikov selectivity, even in the... 

Terminal alkyne an alkyne with a hydrogen attached to a triply bonded carbon. 

It is worth mentioning that some precursors easily catalyze the reductive carbonylation of alkynes from the C0/H20 couple. Here, the main role of water is to furnish hydrogen through the water-gas-shift reaction, as evidenced by the co-production of CO2. In the presence of Pd /KI terminal alkynes have been selectively converted into furan-2-(5H)-ones or anhydrides when a high concentration in CO2 is maintained. Two CO building blocks are incorporated and the cascade reactions that occur on palladium result in a cyclization together with the formation of an oxygen-carbon bond [37,38]. Two examples are shown in Scheme 4. 

Alkynes react readily with a variety of transition metal complexes under thermal or photochemical conditions to form the corresponding 7t-complexes. With terminal alkynes the corresponding 7t-complexes can undergo thermal or chemically-induced isomerization to vinylidene complexes [128,130,132,133,547,556-569]. With mononuclear rj -alkyne complexes two possible mechanisms for the isomerization to carbene complexes have been considered, namely (a) oxidative insertion of the metal into the terminal C-Fl bond to yield a hydrido alkynyl eomplex, followed by 1,3-hydrogen shift from the metal to Cn [570,571], or (b) eoneerted formation of the M-C bond and 1,2-shift of H to Cp [572]. 

After the discovery of the first terminal vinylidene-metal complex in 1972, it was established that the stoichiometric activation of terminal alkynes by a variety of suitable metal complexes led to 1,2-hydrogen transfer and the formation of metal-vinylidene species, which is now a classical organometallic reaction. A metal-vinylidene intermediate was proposed for the first time in 1986 to explain a catalytic anti-Markovnikov addition to terminal alkynes. Since then, possible metal-vinylidene intermediate formation has been researched to achieve catalytic regiose-lective formation of carbon-heteroatom and carbon-carbon bonds involving the alkyne terminal carbon. 

Alkynes are hydrocarbons that contain a carbon-carbon triple bond. A triple bond consists of a cr bond and two tt bonds. The general formula for the alkynes is C li2n-2- The triple bond possesses two elements of unsaturation. Alkynes are commonly named as substituted acetylenes. Compounds with triple bonds at the end of a molecule are called terminal alkynes. Terminal —CH groups are called acetylenic hydrogens. If the triple bond has two alkyl groups on both sides, it is called an internal alkyne. 

The position of the triple bond can alter the reactivity of the alkynes. Acidic alkynes react with certain heavy metal ions, e.g. Ag+ and Cu+, to form precipitation. Addition of an alkyne to a solution of AgNOs in alcohol forms a precipitate, which is an indication of hydrogen attached to the triple bonded carbon. Thus, this reaction can be used to differentiate terminal alkynes from internal alkynes. 

Hydroboration-oxidation of alkynes preparation of aldehydes and ketones Hydroboration-oxidation of terminal alkynes gives syn addition of water across the triple bond. The reaction is regioselective and follows anti-Markovnikov addition. Terminal alkynes are converted to aldehydes, and all other alkynes are converted to ketones. A sterically hindered dialkylborane must be used to prevent the addition of two borane molecules. A vinyl borane is produced with anU-Markovnikov orientation, which is oxidized by basic hydrogen peroxide to an enol. This enol tautomerizes readily to the more stable keto form. 

An anti-Markovnikov hydration of terminal alkynes could be a convenient way of preparing aldehydes, but so far only a few ruthenium-complexes have been identified that catalyze this unusual hydration mode ]16]. The presence of bidentate phosphine ligands ]16b], the coordination of a water molecule stabilized by hydrogen bonding ]16e] and the use of phosphinopyridine ligands ]16f] seem to be of major importance in these processes. 

Each of the syntheses of seychellene summarized in Scheme 20 illustrates one of the two important methods for generating vinyl radicals. In the more common method, the cyclization of vinyl bromide (34) provides tricycle (35).93 Because of the strength of sjp- bonds to carbon, the only generally useful precursors of vinyl radicals in this standard tin hydride approach are bromides and iodides. Most vinyl radicals invert rapidly, and therefore the stereochemistry of the radical precursor is not important. The second method, illustrated by the conversion of (36) to (37),94 generates vinyl radicals by the addition of the tin radical to an alkyne.95-98 The overall transformation is a hydrostannylation, but a radical cyclization occurs between the addition of the stannyl radical and the hydrogen transfer. Concentration may be important in these reactions because direct hydrostannylation of die alkyne can compete with cyclization. Stork has demonstrated that the reversibility of the stannyl radical addition step confers great power on this method.93 For example, in the conversion of (38) to (39), the stannyl radical probably adds reversibly to all of the multiple bond sites. However, the radicals that are produced by additions to the alkene, or to the internal carbon of the alkyne, have no favorable cyclization pathways. Thus, all the product (39) derives from addition to the terminal alkyne carbon. Even when cyclic products might be derived from addition to the alkene, followed by cyclization to the alkyne, they often are not found because 0-stannyl alkyl radicals revert to alkenes so rapidly that they do not close. 

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