Carbocations acid-catalyzed hydration

This elimination reaction is the reverse of acid-catalyzed hydration, which was discussed in Section 6.2. Because a carbocation or closely related species is the intermediate, the elimination step would be expected to favor the more substituted alkene as discussed on p. 384. The El mechanism also explains the general trends in relative reactivity. Tertiary alcohols are the most reactive, and reactivity decreases going to secondary and primary alcohols. Also in accord with the El mechanism is the fact that rearranged products are found in cases where a carbocation intermediate would be expected to rearrange ... 

Mechanism of the acid-catalyzed hydration of an alkene to yield an alcohol. Protonation of the alkene gives a carbocation intermediate that reacts with water. 

Fig. 2 Free energy reaction coordinate profiles for the stepwise acid-catalyzed hydration of an alkene through a carbocation intermediate (Scheme 5). (a) Reaction profile for the case where alkene protonation is rate determining (ks kp). This profile shows a change in rate-determining step as a result of Bronsted catalysis of protonation of the alkene. (b) Reaction profile for the case where addition of solvent to the carbocation is rate determining (ks fcp). This profile shows a change in rate-determining step as a result of trapping of the carbocation by an added nucleophilic reagent.

The results of studies of the acid-catalyzed hydration of oxygen-, sulfur-, seleno-and nitrogen-substituted alkenes and the relevance of this work to partitioning of the corresponding carbocation intermediates (Chart 1) between deprotonation and nucleophile addition was reviewed in 1986.70. We present here a brief summary of this earlier review, along with additional discussion of recent literature. 

Different rate-determining steps are observed for the acid-catalyzed hydration of vinyl ethers (alkene protonation, ks kp) and hydration of enamines (addition of solvent to an iminium ion intermediate, ks increasing stabilization of a-CH substituted carbocations by 71-electron donation from an adjacent electronegative atom results in a larger decrease in ks for nucleophile addition of solvent than in kp for deprotonation of the carbocation by solvent. 

The first step in the mechanism of acid-catalyzed hydration of alkenes is protonation of the double bond to give a carbocation intermediate. 

The acid-catalyzed hydration of propene proceeds through formation of the secondary carbocation and then attack by water to form propanol. 

Very different solvent deuterium isotope effects (SDIE) of (/ch)/( d) = 0.42 and 1.66, respectively, are observed for acid-catalyzed addition of solvent to o-l and 81.50,58 The inverse SDIE for hydration of o-1 is consistent with initial fast and reversible protonation of substrate followed by rate-determining addition of solvent to the protonated benzylic carbocation o-H-l +. The normal primary SDIE on acid-catalyzed hydration of 81 is consistent with a change in mechanism from stepwise, for acid-catalyzed addition of water o-l,50 to concerted for the acid-catalyzed reaction of 81, where the addition of water and hydron occurs at a single reaction stage (kcon, Scheme 47). 

The mechanism of the formation of the tetrahydropyranyl ether (see Figure 23.1) is an acid-catalyzed addition of the alcohol to the double bond of the dihydropyran and is quite similar to the acid-catalyzed hydration of an alkene described in Section 11.3. Dihydropyran is especially reactive toward such an addition because the oxygen helps stabilize the carbocation that is initially produced in the reaction. The tetrahydropyranyl ether is inert toward bases and nucleophiles and serves to protect the alcohol from reagents with these properties. Although normal ethers are difficult to cleave, a tetrahydropyranyl ether is actually an acetal, and as such, it is readily cleaved under acidic conditions. (The mechanism for this cleavage is the reverse of that for acetal formation, shown in Figure 18.5 on page 776.)... 

Like other reactions that involve carbocation intermediates, hydration may take place with rearrangement. For example, when 3,3-dimethylbut-l-ene undergoes acid-catalyzed hydration, the major product results from rearrangement of the carbocation intermediate. 

The properties of cyclopropyl make it an effective aid in the study of transition states to detect whether or not there is significant positive charge development that can interact with a 7r-donor. It was proposed that in cases where the transition states have the character of open carbocations that large (ca. 10 ) c-Pr/Ph rate ratios should accrue, as demonstrated for the comparison of acid-catalyzed hydration of c-PrCH=CH2 to PhCH=CH2 (equation 40). A number of other examples of this behavior have now been demonstrated as collated in Table... 

Acid catalyzed hydration of alkenes is not well suited for laboratory preparation of alcohols. Since the reaction proceeds via carbocation intermediates, mixtures of alcohols may be formed. However, oxymercuration-demercuration of alkenes provides a simple tool for regioselective hydration of alkenes whereby rearrangements are seldom observed. 

At the time when the Ase2 mechanism of the acid-catalyzed hydration of alkenes was finnly established , the reaction of conjugated dienes was also investigated. It was shown that the same mechanism also applietl to dienes (equation 2). The first step is generally reversible but, under well-chosen reaction conditions, the formation of an allylic carbocation by proton addition to one of the two double bonds is rate-limiting. The fast trapping of the carbocation by water in the second step affords the two allylic alcohols conesponding either to a 1,2-addition or to a 1,4-addition. Several pieces of evidence supported this mechanism. 

Three steps are involved in the acid-catalyzed hydration reaction, as shown in Figure 17.6. The first and last are rapid proton-transfer processes. The second is the nucleophilic addition step. The acid catalyst activates the carbonyl group toward attack by a weakly nucleophilic water molecule. Protonation of oxygen makes the carbonyl carbon of an aldehyde or a ketone much more electrophilic. Expressed in resonance terms, the protonated carbonyl has a greater degree of carbocation character than an unprotonated carbonyl. 

Acid-catalyzed hydration (Markovnikov, with carbocations that may rearrange), e.g.. 

Mechanism 6.3 extends the general principles of electrophilic addition to acid-catalyzed hydration. In the first step of the mechanism, proton transfer to 2-methylpropene forms the tert-h xiy cation. This is followed in step 2 by reaction of the carbocation with a molecule of water acting as a nucleophile. The alkyloxonium ion formed in this step is simply the conjugate acid of tert-h xiy alcohol. Deprotonation of the alkyloxonium ion in step 3 yields the alcohol and regenerates the acid catalyst. 

Acid-Catalyzed Hydration of an Alkene Step 1 Protonation of the double bond forms a carbocation. 

Acid-catalyzed hydration reactions occur with Markovnikov orientation. For example, hydration of 2-methyl-2-butene gives 2-methyl-2-butanol, consistent with the intermediacy of the 3° 2-methyl-2-butyl carbocation. Moreover, hydration of 2-methyl-l-butene was also found to produce 2-methyl-2-butanol, and there was no indication of isomerization to 2-methyl-2-butene during hydration. These results suggest, but do not confirm, that the cationic intermediate undergoes nucleophilic attack by water faster than it loses a proton to revert to starting material. ... 

Observation of a good Hammett correlation p = —3.58) for the hydration of p-substituted styrenes suggests that appreciable positive charge is developed on the incipient benzylic carbon atom in the transition structure. A value of -3.2 was found for acid-catalyzed hydration of 2-arylpropenes. ° Both values are somewhat smaller in magnitude than the value expected for a fully developed benzylic carbocation. ... 

This reaction produced none of the rearrangement product (41) that would be expected from acid-catalyzed hydration of the reactant via an intermediate carbocation. 

Acid-catalyzed hydration of alkenes takes place with Markovmkov regiochemistry but may lead to a mixture of constitutional isomers if the carbocation intermediate in the reaction undergoes rearrangement to a more stable carbocation. 

Oxymercutation-demercutation occurs with Markovnikov regiochemistry and results in hydration of alkenes without complication from carbocation rearrangement. It is often the preferred choice over acid-catalyzed hydration for Markovnikov addition. The overall stereochemistry of addition in acid-catalyzed hydration and oxymercuration-demercuration is not controlled—they both result in a mixture of cis and trans addition products. 

Acid-catalyzed hydration of alkenes has limited synthetic utility, however, because the carbocation intermediate may rearrange if a more stable or isoenergetic carbocation is possible by hydride or alkanide migration. Thus, a mixture of isomeric alcohol products may result. 

Rearrangements also occur in the acid-catalyzed hydration of alkenes, especially when a carbocation formed in the first step can rearrange to a more stable carbocation. For example, the acid-catalyzed hydration of 3-methyl-l-butene gives 2-methyl-2-butanol. In this example, the group that migrates is a hydrogen with its bonding pair of electrons, in effect, a hydride ion H . 

Propose a mechanism similar to that proposed for the acid-catalyzed hydration of an alkene involving proton transfer from the acid catalyst to form a carbocation intermediate, rearrangement of the carbocation intermediate to a more stable intermediate, reaction of the more stable carbocation with water to form an oxonium ion, and finally proton transfer from the oxonium ion to water to give the product and regenerate the acid catalyst. Lest you be tempted to use to initiate the reaction, remember that ionization of a strong acid in water generates a hydronium ion and an anion. Hydronium ion and not H is the true catalyst in this reaction. 

In the 1930s, Marvel and co-workers studied the acid-catalyzed hydration of dienynes, and it was this topic that Nazarov revisited in the 1940s and 1950s. He extensively studied this process and demonstrated the cyclization of the intermediate allyl vinyl ketones 7 to 2-cyclopentenones 8 in numerous cases. Mechanistic interpretation of the reaction remained unclear, however, until the studies of Braude and Coles in 1952. " They demonstrated that the formation of 2-cyclopentenones actually proceeds via divinyl ketones (the allyl vinyl ketones in Nazarov s process isomerize in situ), with the intermediacy of carbocations. Thus the modem interpretation of the Nazarov cyclization was bom The acid-catalyzed closure of divinyl ketones 1 to 2-cyclopentenones 3. 

The regiochemistry of acid-catalyzed hydration of alkenes to give alcohols is that predicted by Markovnikov s rule (Sec. 10.4) because the more stable intermediate carbocation is preferentially formed. Sometimes it is desirable to add the elements of water across a carbon-carbon Ti-bond in the opposite regiochemical sense to provide the anti-Markovnikov product (see the Historical Highlight at the end of this chapter). In order to accomplish this goal, a process termed hydroboration-oxidation was developed that involves the reaction of an alkene sequentially with diborane, B2H, and basic hydrogen peroxide (Eq. 10.26). 

You might compare the product of oxymercuration-reduction of 3,3-methyl-l-butene with the product formed by acid-catalyzed hydration of the same alkene (Section 6.3C). In the former, no rearrangement occurs. In the latter, the major product is 2,3-dimethyl-2-butanol, a compound formed by rearrangement. The fact that no rearrangement occurs during oxymercuration-reduction indicates that at no time is a free carbocation intermediate formed. 

Ethers can be prepared through the acid-catalyzed addition of methyl or primary Problems 11.3,11.4,11.15, alcohols to alkenes that can form a stable carbocation upon protonation, via a 11 -16,11.41,11.42,11.43 mechanism analogous to acid-catalyzed hydration of an alkene. 

The stereochemical outcome of acid-catalyzed hydration is similar to the stereochemical outcome of hydrohalogenation. Once again, the intermediate carbocation can be attacked from either side with equal likelihood (Figure 9.4). Therefore, when a new chirahty center is generated, a racemic mixture of enantiomers is expected ... 

In the second step of acid-catalyzed hydration, the carbocation intermediate is planar and can be attacked from either face, leading to a pair of mirror-image products (enantiomers). 

In this reaction, water is added across an alkene in a Markovnikov fashion under acid-catalyzed conditions. As a result, the OH is positioned at the more substituted carbon. To draw a mechanism for this process, recall that the proposed mechanism for acid-catalyzed hydration has three steps (1) protonation to give a carbocation, (2) nucleophilic attack of water to give an oxonium ion, and (3) deprotonation to generate a neutral product. When drawing the first step of the mechanism (protonation), make sure to use two curved arrows and make sure to form the more stable carbocation ... 

The previous section explored how acid-catalyzed hydration can be used to achieve a Markovnikov addition of water across an alkene. The utility of that process is somewhat diminished by the fact that carbocation rearrangements can produce a mixture of products ... 

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