The hydration of alkynes

The direct hydration of a terminal alkyne, with dilute sulphuric acid in the presence of a mercury salt, yields initially an enol which rearranges to the more stable ketone. The regioselectivity of the reaction is consistent with that predicted on the basis of mechanistic theory. 

The conversion of undec-10-ynoic aid to 10-oxoundecanoic acid (Expt 5.91) is the illustrative example. 

With non-terminal alkynes the preparative applications are more limited since a mixture of ketones is usually obtained, the proportions being dependent upon the nature of R1 and R2. 

Heat under reflux for 4 hours a solution of 3 g (0.0165 mol) of undec-10-ynoic acid (Expt 5.23) in 240 ml of glacial acetic add containing 13 ml of concentrated sulphuric acid and 1.4 g of mercury(n) acetate. Dilute the dark coloured solution with 300 ml of water, filter and extract the solution with dichloromethane using a continuous extraction apparatus (Fig. 2.95) (1). Wash the dichloromethane extract carefully with distilled water until the washings are neutral, dry the extract and evaporate on a rotary evaporator. Recrystallise the solid residue from light petroleum (b.p. 60-80 °C) using a little decolourising charcoal. The yield of keto-acid, m.p. 56-57 °C, is 1.65 g (50%). 

(1) Batchwise extraction leads to the formation of stable emulsions which frequently take several days to break. When filling the continuous extraction apparatus, care should be taken to avoid forming an emulsion. 

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Addition of a hydroxy group to alkynes to form enol ethers is possible with Pd(II). Enol ether formation and its hydrolysis mean the hydration of alkynes to ketones. The 5-hydroxyalkyne 249 was converted into the cyclic enol ether 250[124], Stereoselective enol ether formation was applied to the synthesis of prostacyclin[131]. Treatment of the 4-alkynol 251 with a stoichiometric amount of PdCl2, followed by hydrogenolysis with formic acid, gives the cyclic enol ether 253. Alkoxypalladation to give 252 is trans addition, because the Z E ratio of the alkene 253 was 33 1. 

You have had earlier experience with enols m their role as intermediates m the hydration of alkynes (Section 9 12) The mechanism of enolization of aldehydes and ketones is precisely the reverse of the mechanism by which an enol is converted to a carbonyl compound... 

The hydration of alkynes represents a prime example in which simple coordinative activation by transition metal complexation greatly facilitates an otherwise very slow chemical process (Equation (107)). This reaction has been a long-studied problem, but only recently have alternatives to the classical use of catalysts such as Hg(n) salts been sought. These new catalyst systems typically display much enhanced reactivity, and some can mediate an anti-Markovnikov hydration through a novel mechanism (Table 1). 

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 generally accepted pathway for the hydration of alkynes are the generation and subsequent tautomerization of an intermediate enol. The use of fairly concentrated acids, usually H2S04, is necessary to achieve suitable reaction rates. Addition of catalytic amounts of metal salts, however, greatly accelerates product formation. In most cases mercury(II) salts are used. Mercury-impregnated Nafion-H [with 25% of the protons exchanged for Hg(II)] is a very convenient reagent for hydration 35... 

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... 

Because mercuric salts catalyze the hydration of alkynes, they probably are acting as electrophiles. Mercuric salts are known to add to both alkenes... 

The hydration of alkynes is also accomplished by use of catalytic amounts of palladium and gold salts.305 The mildness of this reaction is demonstrated by the preparation of 5-oxo-prostaglandin derivatives (equation 202). In this connection, it should be noted that attempted use of other metal salts to catalyze C—-C triple bond hydrations has met with little success.306... 

Like aldehydes, ketones can be prepared in a number of ways. The following sections detail some of the more common preparation methods the oxidation of secondary alcohols, the hydration of alkynes, the ozonolysis of alkenes, Friedel-Crafts acylation, the use of lithium dialkylcuprates, and the use of a Grignard reagent. 

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 mentioned earlier (Section 45.9.6.2) aqueous solutions of RuC13 xH20 catalyse the hydration of alkynes. Detailed mechanistic studies indicate that the catalytic activity is dependent upon the combined concentrations of [RuCl4(OH2)2] and [RuC13(OH2)]2., 613... 

Mercury(II) salts also catalyze the hydration of alkynes through similar mercurinium intermediates, with the overall process being... 

The latter is thermodynamically favorable because of the very strong carbon-oxygen double bond that is formed. It is kinetically rapid because the enol O—H bond is acidic and readily deprotonated, allowing the proton eventually to find its way to the nearby carbon. More details concerning the process will be upcoming when carbonyl compounds are discussed. Note that the hydration of alkynes is a new synthesis of aldehydes and ketones. 

We encountered enols earlier as intermediates in the hydration of alkynes (see Mechanism 9.2). Enolates, represented as a hybrid of the resonance structures shown, are the conjugate bases of enols. The major enolate contributor is the structure with the negative charge on oxygen. It is, however, the carbanionic character of the a carbon that is responsible for the importance of enolates in organic synthesis, and we will sometimes write the enolate in the form that has the negative charge on carbon to emphasize this. 

Although some synthetic applications of enols are known, their main role is as reactive intermediates. Enols are intermediates in the hydration of alkynes (Section 9.12) and the decarboxylation of (3-keto acids and malonic acid derivatives (Section 18.16), for example. They are intermediates in a number of biochemical processes including glucose metabolism and malonyl coenzyme A biosynthesis. 

The hydration of alkynes can be carried out in less acidic solutions if catalysts such as Hg are used. The kinetics of the reaction in aqueous sulfuric acid are complex, but there is evidence for the formation... 

Synthesis of Methyl Ketones Using Polymeric Supported Sulfonic Add. Newman has shown that Dowex SOW (Impregnated with 1% HgS04) was an efficient catalyst for the hydration of alkynes to the corresponding methyl ketones, snch as in the transformation of 42 to 43 in 98% yield (eq 28). This optimized process required 20% w/w of Dowex 50W to allow the reaction to proceed to completion. This work was later extended through... 

Enols were introduced in Section 9.12 as reactive intermediates in the hydration of alkynes. 

Aldehydes and ketones may also be produced by the hydration of alkynes. If the triple bond is on the last carbon in a carbon atom chain, an aldehyde is produced if the bond is between internal carbons, the result is a ketone. A typical reaction is the commercial preparation of acetaldehyde ... 

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. 

In 2003, Herrmann reported the hydration of alkynes with a NHC-Au compound. This was the first catalytic application involving NHCs in gold... 

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