Ketones alkyne hydration

In general ketones are more stable than their enol precursors and are the products actually isolated when alkynes undergo acid catalyzed hydration The standard method for alkyne hydration employs aqueous sulfuric acid as the reaction medium and mer cury(II) sulfate or mercury(II) oxide as a catalyst... 

Interestingly, the product actually isolated from alkyne hydration is not the vinylic alcohol, or enol (ene + ol), but is instead a ketone. Although the enol is an intermediate in the reaction, it immediately rearranges to a ketone by a process called keto-enol tautomerisni. The individual keto and enol forms are said to be tautomers, a word used to describe constitutional isomers that interconvert rapidly. With few exceptions, the keto-enol tautomeric equilibrium lies on the side of the ketone enols are almost never isolated. We ll look more closely... 

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. 

Having pyrazinylacetylenes in hand, one could convert the alkynyne functionality into the corresponding ketone via hydration [33], Thus, the coupling of iodide 36 and acetylene 37 produced pyrazinylalkyne 38. Subsequent exposure of 38 to aqueous sodium sulfide and aqueous hydrochloric acid in methanol led to ketone 39. Such a maneuver provides additional opportunities for further manipulation of the alkynes derived from the Sonogashira coupling reactions. 

By the example of 34 different alkynes, it was convincingly demonstrated that the product of the treatment of [PtCLJ with CO at 40-110 °C is a very powerful alkyne hydration catalyst some of the reactions are shown on Scheme 9.7 [25], The best medium for this transformation is THF containing 5 % H2O. The reaction can also be performed in a water-organic solvent two-phase system (e.g. with 1,2-dichloroethane), however in this case addition of a tetralkylammonium salt, such as Aliquat 336, is required to facilitate mass transfer between the phases. After the reaction with CO, the major part of platinum is present as H2[ Pt3(CO)6 n], but the catalytic effect was assigned to a putative mononuclear Pt-hydride, [PtHCl(CO)2], presumably formed from the cluster and some HCl (supplied by the reduction of [PtCU]). The hydration of terminal acetylenes follows Markovnikov s mle leading exclusively to aldehyde-free ketones. 

B-ll. Which one of the following is the intermediate in the preparation of a ketone by hydration of an alkyne in the presence of sulfuric acid and mercury(II) sulfate ... 

The addition of water to an alkyne leads to the formation of an unstable vinyl alcohol. These unstable materials undergo keto-enol tautomerization to form ketones. The hydration of propyne forms 2-propanone, as the following figure illustrates. 

Anhydrous iron(III) halides catalyse coupling of alkynes and aldehydes.211 Simple terminal alkynes, R CH, react with aldehydes, R2CHO, to give ( ,Z)-1,5-dihalo-1,4-dienes (55). In contrast, non-terminal arylalkynes give ( ,)-o, /3-unsaturated ketones. The catalysts also promote standard Prins cyclization of homoallylic alcohols. Studies of intermediates and of alkyne hydration - together with calculations - all support FeX3 complex formation with alkyne as the activating step. 

The anthracyciinone class of anticancer compounds (which includes daunomycin and adriamycin) can be made using a mercury (I I )-promoted alkyne hydration. You saw the synthesis of alkynes in this class on Chapter 9 where we discussed additions of metallated alkynes to ketones. Here is the final step in a synthesis of the anticancer compound deoxydaunomycinone the alkyne is hydrated using Hg2+ in dilute sulfuric acid the sulfuric acid also catalyses the hydrolysis of the phenolic acetate to give the final product. 

On the other hand, lithium enolates derived from substituted endocyclic ketones have largely been exploited in the synthesis of steroids since the regioselectivity of their deprotonation can be controlled and high levels of 1,2- and 1,3-stereoselection occur9,418. The control is steric rather than electronic, with the attack directed to the less substituted ji-face of the enolate for conformationally rigid cyclopentanones, whereas stereoelectronic control becomes significant for the more flexible cyclohexanones. Finally, an asymmetric variant of the formation of a-branched ketones by hydration of camphor-derived alkynes followed by sequential alkylation with reactive alkyl halides of the resulting ketones was recently reported (Scheme 87)419. 

The mechanism of the mercurydD-catalyzed alkyne hydration reactioi is analogous to the oxymercuration reaction of alkenes (Section 7.4). Elec trophilic addition of mercury(II) ion to the alkyne gives a vinylic cation which reacts with water and loses a proton to yield a mercury-containii eiio) intermediate. In contrast to alkene oxymercuration, no treatment witll NaBH is necessary to remove the mercury the acidic reaction conditions alone are sufficient to effect replacement of mercury by hydrogen (Figure 8,3), A mixture of both possible ketones results when an unsymmetrically substituted internal alkyne (RCsCR ) is hydrated. The reaction is therefor ... 

Alkynes also imdergo acid-catalyzed hydration to yield ketones. Alkynes substituted with alkoxy or phenoxy groups undergo hydration readily, and butyl acetate was obtained by heating butoxyacetylene in distilled water... 

Aldehydes/Ketones via Alkyne Hydration (RCsCR [enoi] ket/ald)... 

With terminal alkynes, hydration gives the ketone instead of the aldehyde, consistent with Markovnikov addition (Eq. 10.10). When alkynes are treated with strong acids, vinyl cations are formed. Nucleophilic attack by water and deprotonation first give a vinyl alcohol (enol), which ultimately tautomerizes to a ketone. The tautomerization mechanism will be given in the next chapter. 

We have seen that even trace amounts of acid will catalyze a keto-enol tautomerization. Therefore, the enol initially produced by hydration of an alkyne will immediately tautomerize to form a ketone. When asked to predict the product of alkyne hydration, do not make the mistake of drawing an enol. Simply draw the ketone. 

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. 

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