The Addition of Water to an Alkyne

Drawing on what you know about the stereochemistry of alkene addition reactions  

In Section 6.5, we saw that aUcenes undergo the acid-catalyzed addition of water. The product of the electrophilic addition reaction is an alcohol. 

Alkynes also undergo the acid-catalyzed addition of water. 

The initial product of the reaction is an enol. An enol has a carbon-carbon double bond with an OH group bonded to one of the sp carbons. (The suffix ene signifies the double bond, and ol signifies the OH group. When the two suffixes are joined, the second e of ene is dropped to avoid two consecutive vowels, but the word is pronounced as if the second e were still there ene-ol. ) The enol immediately rearranges to a ketone. 

A ketone and an enol differ only in the location of a double bond and a hydrogen. A ketone and its corresponding enol are called keto-enol tautomers. Tautomers ( taw-toe-mers ) are constitutional isomers that are in rapid equilibrium. The keto tautomer predominates in solution, because it is usually much more stable than the enol tautomer. Interconversion of the tautomers is called keto-enol interconversion or tautomerization. 

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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. 

If a simple enol is generated by some reaction, such as the addition of water to an alkyne described in Section 11.6, the enol cannot be isolated because it rapidly converts to the more stable carbonyl tautomer. The lifetime of CH2=CHOH, the simplest enol, is about 1 minute in aqueous solution at pH 7, about 1 second in acidic solution, and about 10-6 second in basic solution. 

At this point, you know only one way to synthesize a ketone—the addition of water to an alkyne (Section 6.6). The alkyne can be prepared from two successive E2 reactions of a vicinal dihalide, which in turn can be synthesized from an alkene. The desired alkene can be prepared from the given starting material by an elimination reaction. 

At this point in your study of organic chemistry, you know only three ways to synthesize a ketone (1) the addition of water to an alkyne (Section 7.7), (2) hydroboration-oxi tion of an alkyne (Section 7.8), and (3) ozonolysis of an alkene (Section 6.12). Because the target molecule has the same number of carbons as the starting material, we can rule out ozonolysis. Now we know that the precursor molecule must be an alkyne. The alkyne needed to prepare the ketone can be prepared from two successive E2 reactions of a vicinal dihahde, which in turn can be synthesized from an alkene. The desired alkene can be prepared from the given starting material by an elimination reaction, using a bulky base to maximize the elimination product... 

Our catalyst for the isomerization of alkenes is going to be HC1 absorbed on to solid alumina (aluminium oxide, AI2O3) and the isomerization is to occur during a reaction, the addition of HC1 to an alkyne, in which the alkenes are formed as products. In this reaction the oxalyl chloride is first mixed with dried alumina. The acid chloride reacts with residual water on the surface (it is impossible to remove all water from alumina) to generate HC1, which remains on the surface. 

When you know what functional group you want to create, you can try to remember the various ways it can be synthesized. For example, a ketone can be synthesized by the acid-catalyzed addition of water to an alkyne, hydroboration-oxidation of an alkyne, oxidation of a secondary alcohol, and ozonolysis of an alkene. Notice that ozonolysis decreases the number of carbons in a molecule. 

Hydration of unactivated alkynes is an important method for functionalizing this plentiful hydrocarbon source. Therefore, a variety of metal ions have been proposed as catalysts for this reaction, and almost all of the reported additions of water to terminal alkynes follow the Markonikov rule. The hydration of l-aUcynes with Hg(II) salts in sulfuric acid [85], RuCh/aq.HCl [86, 87], K[Ru (edta-H)Cl] 2H20 [88], RhCl,.3H20/aq. HCl [89], RhCl3/NR4 [90], Zeise-type Pt(II) complexes [91-93], and NaAuCl4 [94] produced exclusively methyl ketones (Eq. 6.46). 

With an electrophilic transition metal complex, it is believed that the hydration of an alkyne occurs through a trans-addition of water to an 72-alkyne metal complex (Scheme 15, path A),380 although the m-pathway via hydroxymetallation has also been proposed (path B).381,382 However, distinguishing between the two pathways is difficult due to the rapid keto-enol tautomerization that renders isolation of the initial water adduct challenging. 

A most significant advance in the alkyne hydration area during the past decade has been the development of Ru(n) catalyst systems that have enabled the anti-Markovnikov hydration of terminal alkynes (entries 6 and 7). These reactions involve the addition of water to the a-carbon of a ruthenium vinylidene complex, followed by reductive elimination of the resulting hydridoruthenium acyl intermediate (path C).392-395 While the use of GpRuGl(dppm) in aqueous dioxane (entry 6)393-396 and an indenylruthenium catalyst in an aqueous medium including surfactants has proved to be effective (entry 7),397 an Ru(n)/P,N-ligand system (entry 8) has recently been reported that displays enzyme-like rate acceleration (>2.4 x 1011) (dppm = bis(diphenylphosphino)methane).398... 

In fact, a mechanism for this reaction can be drawn that does not involve Pd at all, but let s assume that Pd is required for it to proceed. Cl- must be nucleophilic. It can add to Cl of the alkyne if the alkyne is activated by coordination to Pd(II). (Compare Hg-catalyzed addition of water to alkynes.) Addition of Cl- to an alkyne-Pd(II) complex gives a o-bound Pd(II) complex. Coordination and insertion of acrolein into the C2-Pd bond gives a new a-bound Pd(II) complex. In the Heck reaction, this complex would undergo P-hydride elimination, but in this case the Pd enolate simply is protonated to give the enol of the saturated aldehyde. 

Addition of water to an internal alkyne is not regioselective. When the internal alkyne has identical groups attached to the sp carbons, only one ketone is obtained. For example, 2-butyne reacts with water in the presence of acid catalyst to yield 2-butanone. 

The addition of water to alkynes is also aided by the presence of mercury (II) salts. The reaction is usually conducted in water, with the presence of a strong acid, such as sulfuric acid, and a mercury salt, such as HgS04 oi HgO. In this case the mercury is spontaneously replaced by hydrogen under the reaction conditions, so a second step is not necessary. The addition occurs with a Markovnikov orientation stereochemistry is not an issue. 

Dichloro-5-(l-o-carboranylmethyl)-6-methylpyrimidine (674) is said to be a potential synthon for the preparation of 5-(l-o-carboranylmethyl)-6-methylpyrimidines chemoselective nucleophilic substitution of the chlorine atoms can be effected, and the cage can be selectively degraded for the preparation of more water-soluble Wo-undecarborate derivatives. Preparation of the target molecule (674) is effected by the addition of decaborane to an appropriate alkyne (673) as shown in Equation (19) <9lJOC2391>. 

Addition of water to an internal alkyne that has the same group attached to each of the sp carbons forms a single ketone as a product. But if the two groups are not... 

The mechanism of nitrile hydrolysis involves acid or base promoted addition of water across the triple bond. This gives an intermediate imidate that tautomerizes to an amide. The amide is then hydrolyzed to the carboxylic acid. The addition of water to the nitrile resembles the hydration of an alkyne (eq. 3.52). The oxygen of water behaves as a nucleophile and bonds to the electrophilic carbon of the nitrile. Amide hydrolysis will be discussed in Section 10.20. 

Hydration of alkynes (Section 9.12) Reaction occurs by way of an enol intermediate formed by Markovnikov addition of water to the triple bond. 

In 1998, Wakatsuki et al. reported the first anti-Markonikov hydration of 1-alkynes to aldehydes by an Ru(II)/phosphine catalyst. Heating 1-alkynes in the presence of a catalytic amount of [RuCljlCgHs) (phosphine)] phosphine = PPh2(QF5) or P(3-C6H4S03Na)3 in 2-propanol at 60-100°C leads to predominantly anti-Markovnikov addition of water and yields aldehydes with only a small amount of methyl ketones (Eq. 6.47) [95]. They proposed the attack of water on an intermediate ruthenium vinylidene complex. The C-C bond cleavage or decarbonylation is expected to occur as a side reaction together with the main reaction leading to aldehyde formation. Indeed, olefins with one carbon atom less were always detected in the reaction mixtures (Scheme 6-21). 

Hexyne has the triple bond in the middle of a carbon chain and is termed an internal alkyne. If, instead, an alkyne with the triple bond at the end of the carbon chain, a 1-alkyne or a terminal alkyne, were used in this reaction, then the reaction might be useful for the synthesis of aldehydes. The boron is expected to add to the terminal carbon of a 1-alkyne. Reaction with basic hydrogen peroxide would produce the enol resulting from anti-Markovnikov addition of water to the alkyne. Tautomerization of this enol would produce an aldehyde. Unfortunately, the vinylborane produced from a 1-alkyne reacts with a second equivalent of boron as shown in the following reaction. The product, with two borons bonded to the end carbon, does not produce an aldehyde when treated with basic hydrogen peroxide. 

Section 11.6 discussed the acid-catalyzed addition of water to alkynes. The initial product of this reaction, called an enol, has a hydroxy group attached to one of the carbons of a CC double bond. The enol is unstable and rapidly converts to its tautomer, a carbonyl compound. The carbonyl and enol tautomers of acetone are shown in the following equation ... 

As described in the section Reactions Involving Addition of Water to Alkynes, the reaction of terminal alkynes, water, and a-vinyl ketones afforded 1,5-diketones in DMF-H20 (Eq. 12). Under similar conditions, in the presence of halide, ruthenium-catalyzed three-component coupling of alkyne, an enone, and halide ion formed vinyl halide (Eq. 17) [35]. 

In contrast to the addition of water, the addition of alcohols to alkynes leads to stable enol ethers. Those of economic importance are almost exclusively the vinyl ethers prepared from acetylene. This preparation is carried out under base catalysis [41] (KOH, alcoholates, and the like). The noble metal-catalyzed alcohol addition does in fact likewise lead, in an intermediate stage, to vinyl ethers, but these react under the prevailing conditions, generally in a quantitative reaction, to give to corresponding acetaldehyde dialkyl acetals [42]. This is illustrated in (eq. (18)), which takes as its example the addition of n-butanol to acetylene in the presence of Na2PtCl6. 

Many chemists find that the easiest way to design a synthesis is to work backward. Instead of looking at the starting material and deciding how to do the first step of the synthesis, look at the product and decide how to do the last step. The product is a ketone. At this point the only reaction you know that forms a ketone is the addition of water (in the presence of a catalyst) to an alkyne. If the alkyne used in the reaction has identical substituents on each of the sp carbons, only one ketone will be obtained. Thus, 3-hexyne is the best alkyne to use for the synthesis of the desired ketone. 

When an alkyne undergoes the acid-catalyzed addition of water, the product of the reaction is an enol. The enol immediately rearranges to a ketone. A ketone is a compound that has two alkyl groups bonded to a carbonyl (C=0) group. An aldehyde is a compound that has at least one hydrogen bonded to a carbonyl group. The ketone and enol are called keto-enol tautomers they differ in the location of a double bond and a hydrogen. Interconversion of the tautomers is called tautomerization. The keto tautomer predominates at equilibrium. Terminal alkynes add water if mercuric ion is added to the acidic mixture. In hydroboration-oxidation, H is not the electrophile, H is the nucleophile. Consequently, mercuric-ion-catalyzed addition of water to a terminal alkyne produces a ketone, whereas hydroboration-oxidation of a terminal alkyne produces an aldehyde. 

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