Mechanism alkyne hydration

Reaction of acetone with D30+ yields hexadeuterioacetone. That is. all the hydrogens in acetone are exchanged for deuterium. Review the mechanism of mercuric ion-catalyzed alkyne hydration, and then propose a mechanism for this deuterium incorporation. 

Experiments with terminal acetylenes, isolation of an intermediate acetal, alkyne hydratation studies, and ab initio calculations provide substantiation of a unified mechanism that rationalizes the reactions in which the complex formation between the alkyne and the iron(III) halides is the activating step (Scheme 12) [27]. 

We are applying the principles of enzyme mechanism to organometallic catalysis of the reactions of nonpolar and polar molecules for our early work using heterocyclic phosphines, please see ref. 1.(1) Here we report that whereas uncatalyzed alkyne hydration by water has a half-life measured in thousands of years, we have created improved catalysts which reduce the half-life to minutes, even at neutral pH. These data correspond to enzyme-like rate accelerations of >3.4 x 109, which is 12.8 times faster than our previously reported catalyst and 1170 times faster than the best catalyst known in the literature without a heterocyclic phosphine. In some cases, practical hydration can now be conducted at room temperature. Moreover, our improved catalysts favor anti-Markovnikov hydration over traditional Markovnikov hydration in ratios of over 1000 to 1, with aldehyde yields above 99% in many cases. In addition, we find that very active hydration catalysts can be created in situ by adding heterocyclic phosphines to otherwise inactive catalysts. The scope, limitations, and development of these reactions will be described in detail. 

Moreover, contrary to alkyne hydration where no adsorption of the carbonyl compound was detected, the problem is complicated here by the saturation of the strong acidic sites by the formed amide, the concentration of which shows a rapid stabilization against time (Fig.3). Consequently the reaction selectivity greatly depends on the ester percentage. The behaviour of the amide itself over the studied zeolites confirms this observation the conversion of the amide into ester goes faster on the HY2 g zeolite than on the Hg and on the HMg zeolites. This later point, together with the comprehension of the different mechanisms in relation with the zeolite properties, will be discussed in a further paper. 

Isotope effect studies of the mechanism of hydration of alkynes with formic acid as water donor485b,485c leading to ketones (equation 234a) have been undertaken recently4854 by observing the kinetic isotope fractionation of 13C in the course of carbon monoxide... 

This alkyne hydration reaction can occur without added Hg2+. Show all the steps in the mechanism. 

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 enol intermediate. In contrast to alkene oxymercuration, no treatment widi NaBH4 is necessary to remove the mercury the acidic reaction conditions alone are sufficient to effect replacement of mercury by hydrogen (Figure 8.3). 

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. 

In 2003, the Uemura group reported a diversity-oriented approach to highly substituted furans based on ruthenium- and platinum-catalyzed intramolecular annulation of propargylic alcohols 59 and ketones 60 (Scheme 19.28) [22]. This reaction is related to the aforementioned pyrrole synthesis (Scheme 19.13). Based on the time profile of the reaction, in which rapid formation/consumption of the alk-4-yn-l-one 63 was seen but only gradual formation/consumption of the diketone 122 was observed, they proposed a mechanism including alkyne hydration and subsequent cyclization of the resulting diketones. However, this reaction can be considered as a furan synthesis by formal reaction between the C=0 and alkyne groups. 

Fig. 4.20 Mechanism of alkynes hydration. (From O.N. Temidn, Kinetic models of multi-route reactions in homogeneous catalysis with metal complexes (a review), Kinet. Catal. 53 (2012) 313—343. Copyright 2012...

Further elucidations on the mechanism of alkynes hydration arise from the isolation of both enol and keto tautomers of organometallic intermediates, starting from an alkyne-carboxylic acid ester as tetrolic acid ethyl ester [43]. 

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 rates of bromination of dialkylacetylenes are roughly 100 times greater than for the corresponding monosubstituted alkynes. For hydration, however, the rates of reaction are less than 10 times greater for disubstituted derivatives. Account for this observation by comparison of the mechanisms for bromination and hydration. 

Figure 8.3 MECHANISM Mechanism of the mercury(II)-catalyzed hydration of an alkyne to yield a ketone. The reaction occurs through initial formation of an intermediate enol, which rapidly tautomerizes to the ketone.

Excess acidity correlations have been used to show that some aromatic sulfonic acid desulfonations have an A-SE2 mechanism.188,189 This mechanism (alternative terminologies are Ad-E2 and A(E) +A(N))190 has also been found to apply to the hydration of acetylene itself,191 to ynamines192 and to many other alkynes,193-195 as well as to many different alkenes196-199 and vinyl ethers.200-203 The excess acidity method has been used to evaluate aA values for several alkene hydrations.204 205... 

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 of olefins, alkynes and nitriles calls explicitely for the use of aqueous solvents. Indeed, one of the earliest investigations originates from 1969, when hydration of fluoroalkenes were studied with Ru(II)-chloride catalysts (Scheme 9.6). The reaction has no synthetic value but the studies helped to clarify the mechanism of the interaction of olefins with Ru(II)... 

This reaction achieves an umpolung cyclization in vhich a terminal alkyne is hydrated and undergoes an intramolecular Michael addition according to the mechanism depicted in Scheme 6.34. 

Scheme 10.7 A mechanism proposed for the anti-Markovnikov hydration of alkynes.

Mercury(II) oxide and acetic acid effect the cyclization of l,4-diaryloxybut-2-ynes to 4-aryloxymethylchromenes. The transformation was attributed to cyclization of the butanone which resulted from hydration of the alkyne (72JHC489). However, it has since been shown that similar butanones do not cyclize to chromenes under the cyclization conditions (78JOC3856). Instead, a mechanism is proposed which involves a charge-induced Claisen rearrangement which is triggered by 7r-complex formation between the metal ion... 

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 ... 

The reaction was rationalized by a ruthenium enolate mechanism (Fig. 4). Water served as a nucleophile and added to alkynes then the intermediate isomerized to give a ruthenium enolate, which then underwent addition to a-vinyl ketone followed by protonation to afford the 1,5-diketone. During the reaction, no ketone resulting from the hydration of the alkynes was found, which showed that the conjugate addition is faster than protonation of the ruthenium enolate in this aqueous reaction. 

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