Organic Chemistry: Concepts and Applications - Headley Allan D. 2020
Addition Reactions Involving Alkenes and Alkynes
8.6 Addition of Water to Alkenes (Hydration of Alkenes)
As demonstrated earlier, addition reactions involving H-Cl across the double bond involve the formation of a carbocation intermediate. The mechanism of those addition reactions can be used to explain the outcome of the addition reaction of H-OH across a double bond. Water is a polar molecule in which the hydrogen is partially positive and the OH group is partially negative. Thus, the partially positive hydrogen would act as an electrophile and the OH group as the nucleophile for an addition reaction to the carbon—carbon double bonds of alkenes, as illustrated in Reaction (8-52).
(8-52)
It turns out that water is a very stable molecule, and as a result, a catalyst is needed for this type of addition reaction to proceed. The catalyst in this case is an acid (H+), and the first step of the reaction mechanism is shown in Reaction (8-53) in which the electrophilic proton of the catalyst adds to the nucleophilic alkene to form a carbocation.
(8-53)
In the next step of the reaction mechanism, the nucleophilic water reacts with the electrophilic carbocation, as shown in Reaction (8-54).
(8-54)
Notice that since one pair of the electrons from water is used to bond with the electrophilic carbocation forming a new covalent bond, the oxygen acquires a formal charge of positive one (+1). The newly formed intermediate carries a positive charge and in the next step of the reaction mechanism deprotonation occurs to produce a neutral organic product and regenerates a proton, which is essentially the catalyst, as shown in Reaction (8-55).
(8-55)
Hence, the catalyst proton is used in the first step of the reaction, but is regenerated in the last step of the reaction mechanism. The overall reaction mechanism is shown in Reaction (8-56).
(8-56)
A challenge that is encountered for the addition to unsymmetrical alkenes is to predict the major addition product. A basic concept for these reactions is that the reaction will proceed via the more stable cation to give the major product; thus, the key is to determine the most stable carbocation. For the addition of water to methylcyclohexene, the reaction mechanism is shown in Reaction (8-57), in which the more stable tertiary carbocation is formed.
(8-57)
Problem 8.9
Give the major organic product that results from addition of water in the presence of an acid catalyst to the alkenes shown below.
Another challenge that exists in determining the products for the catalytic addition of water across the double bond of an alkene is that rearrangement of the intermediate carbocation is possible giving rise to unexpected products, as in the example in Reaction (8-58).
(8-58)
1-Methylcyclohexanol is an unexpected product and a closer look at the reaction mechanism will help explain its formation. In the first step of the reaction mechanism, the pi (π) electrons react with the catalyst (H+) to form a secondary carbocation as shown in Reaction (8-59).
(8-59)
Since the carbocation formed is a secondary carbocation and can rearrange, it will rearrange to give a more stable tertiary carbocation. Such a rearrangement is possible by the migration of a hydride ion (H−) from the adjacent carbon to form the more stable tertiary carbocation as shown in Reaction (8-60).
(8-60)
Note that the migrating hydride anion moves with its bonding electrons and that explains the charge left behind after the migration has occurred as a positive charge on the carbon, resulting in the formation of a stable tertiary carbocation. In the next step of the reaction mechanism, the nucleophilic water bonds to the carbocation to form a protonated alcohol intermediate, as shown in Reaction (8-61).
(8-61)
The last step of the reaction mechanism involves the loss of a proton to form the final product as shown in Reaction (8-62).
(8-62)
One of the products of the reaction of 3,3-dimethylcyclohexene with water in the presence of an acid catalyst is an unexpected hydration product as shown in Reaction (8-63).
(8-63)
A close examination of the reaction mechanism reveals that there is a migration of a methyl group with its electron (methide ion) to form a more stable carbocation as shown in Reaction (8-64).
(8-64)
In the final steps of the reaction mechanism, water reacts with the tertiary carbocation to form a protonated alcohol, which is deprotonated in a final step to form the unexpected alcohol as shown in Reaction (8-65).
(8-65)
Problem 8.10
Propose a reasonable mechanism to explain the formation of the rearranged products shown for the following hydration reactions.
For the hydration of alkenes, it is obvious that it is sometimes difficult to predict the Markovnikov addition product since rearrangement often times occurs. As a result, there is a challenge if the Markovnikov addition product is the desired product for a particular addition reaction. In the next section, specific strategies to achieve the goal of obtaining one product as the major organic product will be discussed.
8.6.1 Hydration by Oxymercuration—Demercuration
As shown in the previous section, a major problem encountered in trying to achieve the synthesis of a specific hydration product is that rearrangement sometimes occurs, which often gives unexpected products. One way to get around possible rearrangement is to examine the mechanism of another route to add water across a double bond. Mercury ions can add across a carbon—carbon double bond to form a bridged relatively stable intermediate, similar to the bromonium ion that was encountered in the bromination of alkenes. Recall that due to the size of the bromine atom, the charge of the carbocation is distributed across three atoms: the two carbons of the alkene and bromine, see Reaction (8-43). Owing to the stability of the bromonium ion, no rearrangement occurs. The addition of an electrophilic mercury (in the form of mercury acetate), which is fairly large and polarizable, to a double bond leads to a similar stable bridged mercury cationic intermediate as shown in Reaction (8-66).
(8-66)
This bridged mercury cationic intermediate is fairly stable due to the size of the large polarizable mercury and the positive charge that is distributed throughout the three atoms of the bridged intermediate. One carbon of this bridged mercury cationic intermediate, however, has a greater positive character than the other carbon, and the carbon that has the greater number of alkyl substitution bonded to that carbon is more carbocationic-like, compared to the other carbon with less alkyl groups. In other words, the carbon that is more tertiary-like carries a greater positive character, compared to another carbon that is secondary or primary. Thus, an attack by a nucleophile, such as water, will occur at the carbon that bears the most alkyl groups, and the intermediate that results will have the mercury acetate bonded to the adjacent carbon, as shown in Reaction (8-67).
(8-67)
In a second reaction, the mercury acetate can be removed by a reduction reaction with a strong reducing agent such as NaBH4, as shown in Reaction (8-68).
(8-68)
Thus, the overall reaction that results from the addition of water across a double bond, by introducing mercury acetate, and then removing the mercury salt is shown in Reaction (8-69).
(8-69)
Since the strategy used in this type of reaction is to introduce a mercury salt to stabilize the intermediate formed, then removing it, this reaction is often referred to as oxymercuration—demercuration. Note that the result of this addition reaction is a Markovnikov addition of water to a double bond and that there is no rearrangement for this type of reaction. A specific example oxymecuration—demercuration (hydration) is shown in Reaction (8-70).
(8-70)
Note that in the reaction mechanism, the attack of the water on the bridged mercury ion takes place to give the trans-product, but stereochemistry at the carbon that has the mercury acetate is lost during the reduction step of the reaction sequence. As a result, these reactions are not considered to be stereospecific, and racemic mixture of the enantiomers will result as the products as shown in Reaction (8-71).
(8-71)
Problem 8.11
Give the major organic products for the following hydration reactions.
Thus, oxymercuration—demercuration reactions give no rearrangement and the addition takes place in a regiospecific manner by the Markovnikov addition rule and these reactions are not considered to be stereospecific.
8.6.2 Hydration by Hydroboration-Oxidation
A question that comes to mind at this point is it possible to add water to alkenes in an anti-Markovnikov manner? In this case, a different strategy will have to be used, which of course cannot involve the formation of carbocation intermediates since carbocation intermediates result in Markovnikov addition. A different approach will have to be taken and this involves the use of borane (BH3), which exists as a dimer as shown in Reaction (8-72).
(8-72)
This molecule is actually a Lewis acid, with boron being sp2 hybridized and having a vacant p orbital, it can accept electrons into the vacant p orbital. If another molecule of borane is close, the bonding electrons from the B─H bonds attempt to share its bonding electrons with the empty p orbital on the boron and the result is the dimer and the bonds are shown as partial B─H bonds (as shown in Reaction 8-72). As a result, the above equilibrium involving the diborane and its monomer, as shown above, lies to the right, but in the presence of a Lewis base solvent, such as tetrahydrofuran (THF), it forms a stable complex as shown in Reaction (8-73).
(8-73)
Since the BH3 is electron deficient, it will add across the double bond of the alkene. As shown in the Reaction (8-74), BH3 adds across the double bond to form the product shown.
(8-74)
Note that the borane (BH2-H) adds to the same side of the double bond, resulting in an addition that is described as a cis addition. For an unsymmetrical alkene, there are two ways that the cis addition of borane to the double bond can take place to give two different cis products as shown in Reaction (8-75).
(8-75)
The stability of the products is a factor in determining which product is the major product. As shown in Reaction (8-75), the first product is more stable than the second product due to less steric interaction between the borane group and the two hydrogens on the adjacent carbon. For the second product, there is steric interaction between the borane and the alkyl groups on the adjacent carbon. Similar steric interactions played an important role in the stability of conformers. As demonstrated in Chapter 4, large bulky groups prefer not to be close to each other. Thus, due to steric interactions, the first product is more stable, and hence the major product, compared to the second product, which is less stable. Shown in Reaction (8-76) is a reaction involving the addition of borane to 2-methyl-2-pentene showing the major and minor products.
(8-76)
The initial intent in considering these types of reactions is the addition H-OH across the carbon—carbon double bond to give the anti-Markovnikov product. The products shown in the above reaction can be converted to alcohols by oxidation of the borane functionality of the molecules, as shown in Reaction (8-77), in which hydrogen peroxide (H2O2) is used as the oxidizing agent.
(8-77)
It is always important to know how reactions work (the mechanism) so that if similar reactions are encountered later in this course, they will not present a challenge to predict possible products. In the first step of the mechanism for the oxidation reaction, the peroxide anion is produced in the presence of hydrogen peroxide and a base, such as sodium hydroxide as shown in Reaction (8-78).
(8-78)
In a second step, the peroxide anion reacts with the vacant p orbital of the borane, followed by migration of the alkyl group to the electron-deficient oxygen as shown in Reaction (8-79) to eventually give the final product.
(8-79)
Reaction (8-80) shows the overall two-step reaction sequence in which an alkene is converted to an alcohol by the addition of essential H-OH across the double bond, but in an anti-Markovnikov manner using the hydroboration—oxidation reaction.
(8-80)
For the hydration (addition of H-OH) of alkenes in which the hydroboration—oxidation reaction is used, there is no rearrangement. The addition takes place in a regiospecific manner by the anti-Markovnikov addition, and the reaction is stereospecific to give the cis addition.
Problem 8.12
Give the major organic product of the reactions shown below.
