Acid-catalyzed hydration of alkynes

Other cations (Cu2+, Pd2+, Ru3+, Ni2+, Rh3+) incorporated into Nafion-H have been found to promote hydration.36 Other metals that catalyze hydration of alkynes include gold(III),37 ruthenium(in),38 and platinum(II) (Zeise s salt39 40 and halides40), p-Methoxybenzenetellurinic acid is very effective in the hydration of terminal alkynes 41 Similar to the hydration of alkenes, photochemical acid-catalyzed hydration of alkynes is possible ... 

This reaction was first reported by Fittig and Schrohe in 1875 and subsequently extended by Kutscheroff in 1881. It is an acid-catalyzed hydration of alkynes into ketones. In this reaction, dilute sulfuric acid and mercuric salt are used as catalysts, and mercuric chloride can form a complex with acetylene in aqueous solution. This reaction has been used to prepare ketones from higher alkynes, such as propyne, and vinylacetylene as well as in commercial production of acetaldehyde from acetylene. ... 

The acid-catalyzed hydration of alkynes (Table 6.7, example 2) is commonly carried out using mercury (11) salts, such as mercuric sulfate (HgS04), as catalysts. The addition (Scheme 6.67) appears to involve a bridged mercurinium ion, which, for unsymmetrical cases such as 1-alkynes other than ethyne (acetylene [HC CH]), is subsequently attacked by water (FI2O) at the carbon that best supports a positive charge. The regiochemistry of Markownikoff addition, seen with alkenes, is followed. 

Acid-catalyzed hydration of alkynes is catalyzed by mercuric sulfate (HgS04) to produce an enol that cannot be isolated because it is rapidly converted into a ketone. 

The initial product has a hydroxy group attached to a carbon-carbon double bond. Compounds such as this are called enols (ene + ol) and are very labile—they cannot usually be isolated. Enols such as this spontaneously rearrange to the more stable ketone isomer. The ketone and the enol are termed tautomers. This reaction, which simply involves the movement of a proton and a double bond, is called a keto—enol tautomerization and is usually very fast. In most cases the ketone is much more stable, and the amount of enol present at equilibrium is not detectable by most methods. The mechanism for this tautomerization in acid is shown in Figure 11.6. The mercury-catalyzed hydration of alkynes is a good method for the preparation of ketones, as shown in the following example ... 

Hydration of an internal alkyne with strong acid forms an enol by a mechanism similar to that of the acid-catalyzed hydration of an alkene (Section 10.12). Mechanism 11.4 illustrates the hydration of 2-butyne with H2O and H2SO4. Once formed, the enol then tautomerizes to the more stable keto form by protonation followed by deprotonation. 

The mercuric ion-catalyzed hydration of alkynes probably proceeds in a similar manner to the oxymercuration of alkenes (see Section 5.1). Electrophilic addition of Hg to the triple bond leads to a vinylic cation, which is trapped by water to give an vinylic organomercury intermediate. Unlike the alkene oxymercuration, which requires reductive removal of the mercury by NaBH4, the vinylic mercury intermediate is cleaved under the acidic reaction conditions to give the enol, which tautomerizes to the ketone. Hydration of terminal alkynes follows the Mai kovnikov rule to furnish methyl ketones. ° ... 

Steps 1 and 2 are the same and give 1-heptyne. Instead of acid-catalyzed hydration of 1-heptyne, treat the alkyne with (sia)2BH followed by alkaline hydrogen peroxide (Section 7.7). 

A final case deals, in some more detail, with the acid catalyzed hydration of ethylenes and acetylenes. The reactivity ratio between two pairs of similarly substituted alkenes and alkynes is very much near unity(18), contrary to what expected from the large difference in stability of carbonium ions and vinyl cations. One explanation maintains that the two intermediates ions 1 and 2 are... 

Acid-catalyzed hydration of unsymmetrical internal alkynes yields a mixture of ketones ... 

Acid-catalyzed hydration of a terminal alkyne produces a methyl ketone, while hydroboration-oxi-dation produces an aldehyde. In other words, the regiochemical outcome of alkyne hydration can be controlled by the choice of reagents. Let s get some practice determining which reagents to use. 

Ketones can be prepared via oxidation of secondary alcohols, ozonolysis of alkenes, acid-catalyzed hydration of terminal alkynes, or Friedel-Crafts acylation. 

PROBLEM 10.23 Draw a mechanism for the acid-catalyzed hydration of an alkyne. 

From what you have learned about enols and the hydration of alkynes, predict what product is formed by the acid-catalyzed hydration of CH3CH2CH2C = COCH3. Draw a stepwise mechanism that illustrates how it is formed. 

Also, avoid using steps for which yon have no control over the regiochemical outcome or the stereochemical outcome. For example, acid-catalyzed hydration of the following alkyne will produce two different ketones. 

Acid catalyzed hydration (Section 9 12) Water adds to the triple bond of alkynes to yield ketones by way of an unstable enol intermediate The enol arises by Markovnikov hydration of the alkyne Enol formation is followed by rapid isomerization of the enol to a ketone... 

Alkynes react when heated with trifluoroacetic acid to give addition products. Mixtures of syn and anti addition products are obtained. Similar addition reactions occur with trifluoromethanesulfonic acid. These reactions are analogous to acid-catalyzed hydration and proceed through a vinyl cation intermediate. 

The most synthetically valuable method for converting alkynes to ketones is by mercuric ion-catalyzed hydration. Terminal alkynes give methyl ketones, in accordance with the Markovnikov rule. Internal alkynes give mixtures of ketones unless some structural feature promotes regioselectivity. Reactions with Hg(OAc)2 in other nucleophilic solvents such as acetic acid or methanol proceed to (3-acetoxy- or (3-methoxyalkenylmercury intermediates,152 which can be reduced or solvolyzed to ketones. The regiochemistry is indicative of a mercurinium ion intermediate that is opened by nucleophilic attack at the more positive carbon, that is, the additions follow the Markovnikov rule. Scheme 4.8 gives some examples of alkyne hydration reactions. 

Pt-catalyzed hydration of various aliphatic and aromatic alkynes under phase transfer conditions in (CH2C1)2/H20 in the presence of Aliquat 336 led to either a Markovnikov product, mixtures of two ketones, or ketones with the carbonyl group positioned away from the bulky side.72 In the absence of the phase transfer reagent, Aliquat 336, hardly any reaction took place. Recently, a hydrophobic, low-loading and alkylated polystyrene-supported sulfonic acid (LL-ALPS-SO3H) has also been developed for the hydration of terminal alkynes in pure water, leading to ketones as the product.73 Under microwave irradiation, the hydration of terminal arylalkynes was reported to proceed in superheated water (200°C) without any catalysts.74... 

Hydration and Hydroalkoxylation of Alkynes Gold compounds were first applied to catalyze these types of reactions by Utimoto et al. in 1991, when they studied the use of Au(III) catalysts for the effective activation of alkynes. Previously, these reactions were only catalyzed by palladium or platinum(II) salts or mercury(II) salts under strongly acidic conditions. Utimoto et al. reported the use of Na[AuCI41 in aqueous methanol for the hydration of alkynes to ketones [13]. 

The impressive activity achieved by Teles catalyst was improved some years later by the use of CO as an additive [92]. In this study, Hayashi and Tanaka reported a TOF of 15600h 1, at least two orders of magnitude higher than [as-PtCl2(tppts)2], for the hydration of alkynes, providing an alternative synthetic route to the Wacker oxidation. Although several solvents were tested, the best results were obtained with aqueous methanol, and sulfuric acid or HTfO as acidic promoters. Unlike Utimoto s observation, in this case terminal propargylic alcohols partially (17-20%) delivered anti-Markovnikov product, in addition to the Markovnikov species. Some years before, Wakatsuki et al. had already reported the anti-Markovnikov hydration of terminal alkynes catalyzed by ruthenium(II) [93]. 

The use of silica-supported Zn(BH4)2 is a useful procedure for the hydration of unactivated alkenes and alkynes.559 The main products are usually formed as a result of anti-Markovnikov addition. In contrast to acid-catalyzed hydration (see Section 6.1.2), this procedure allows the transformation of alkynes to alcohols. 

A highly regioselective, efficient, and clean anti-Markovnikov hydration of terminal acetylenes has been realized through the use of catalytic amounts of Ru complexes.561 Typically, [CpRu(dppm)Cl] catalyzes the reaction at 100°C to give aldehydes in high yields (81-94%). Triflic acid or trifluoromethanesulfonimide effectively catalyzes the hydration of alkynes without a metal catalyst to afford Markovnikov products (ketones).562... 

Several preparative methods exist for the synthesis of 3(2//)-dihydrofuranones. 2,5-Disubstituted or 2,2,5,5-tetrasubstituted 3(2i/)-dihydrofuranones are usually prepared by reaction of sodium or lithium acetylide with a ketone to yield an alkynic alcohol which is then treated with a carbonyl compound in the presence of base to afford alkynic diols. Mercury catalyzed hydration of the resultant diols in the presence of acid affords the furanones in good yields (76JMC709). 

Mercuric sulfate catalyzed hydration of cyclopropylacetylenes in aqueous sulfuric acid, like other monosubstituted alkynes, gave mainly the corresponding methyl ketone accompanied by small amounts of ring-opened prouducts (equation 168)236. Similar results were obtained using HgO in trichloroacetic acid, with catalytic amounts of BF3-Et20 and methanol. 

Except for very reactive alkynes, acid-catalyzed hydrations are usually sluggish. This slow hydration can be overcome by the addition of catalytic amounts of mercury(II) salts. Such hydrations are generally mild and will tolerate the presence of other functional groups. Specific examples of mercury-catalyzed hydrations are discussed in the next section. 

Mercuric Ion-Catalyzed Hydration Alkynes undergo acid-catalyzed addition of water across the triple bond in the presence of mercuric ion as a catalyst. A mixture of mercuric sulfate in aqueous sulfuric acid is commonly used as the reagent. The hydration of alkynes is similar to the hydration of alkenes, and it also goes with Markovnikov orientation. The products are not the alcohols we might expect, however. 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

Like the double bond, the carbon-carbon triple bond is susceptible to many of the common addition reactions. In some cases, such as reduction, hydroboration and acid-catalyzed hydration, it is even more reactive. A very efficient method for the protection of the triple bond is found in the alkynedicobalt hexacarbonyl complexes (.e.g. 117 and 118), readily formed by the reaction of the respective alkyne with dicobalt octacarbonyl. In eneynes this complexation is specific for the triple bond. The remaining alkenes can be reduced with diimide or borane as is illustrated for the ethynylation product (116) of 5-dehydro androsterone in Scheme 107. Alkynic alkenes and alcohols complexed in this way show an increased structural stability. This has been used for the construction of a variety of substituted alkynic compounds uncontaminated by allenic isomers (Scheme 107) and in syntheses of insect pheromones. From the protecting cobalt clusters, the parent alkynes can easily be regenerated by treatment with iron(III) nitrate, ammonium cerium nitrate or trimethylamine A -oxide. ° ... 

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