10.4:
Preparation of Alcohols via Addition Reactions
Alcohols can be prepared through the reaction of alkenes with water using three synthetic routes: acid-catalyzed hydration, oxymercuration–demercuration, and hydroboration–oxidation.
In the acid-catalyzed hydration of alkenes, a proton is added to the less-substituted carbon in the double bond, forming a more stable carbocation. Subsequently, hydroxyl is added to the more substituted end of the double bond, which follows Markovnikov's rule.
Since a trigonal planar carbocation intermediate is involved in the reaction pathway, the addition of the water molecule on either face is equally probable, and a racemic mixture of alcohols is formed.
Alcohol synthesis via oxymercuration–demercuration of alkenes does not have a conventional carbocation intermediate. Instead, the nucleophilic attack of the double bond on the positively-charged mercury acetate creates a three-membered mercurinium ion intermediate, which can be considered a resonance hybrid with minor carbocation character.
The subsequent hydration of the mercurinium ion is consistent with Markovnikov's rule. Following proton transfer, sodium borohydride replaces the mercury species with a proton to give the final product — alcohol.
Alcohols can also be synthesized via the hydroboration–oxidation reaction. Here, borane adds to the double bond of an alkene to form an alkyl borane transition state.
Boron acquires a partial negative charge, and the carbon on the opposite end acquires a partial positive charge. Due to the steric effects, borane addition occurs at the less substituted carbon, which also stabilizes the partial positive charge on the more substituted carbon, forming an alkylborane.
Further, two more alkene molecules sequentially add to give a trialkyl borane, which upon further oxidation with hydrogen peroxide and sodium hydroxide results in an anti-Markovnikov product.
10.4:
Preparation of Alcohols via Addition Reactions
Overview
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation intermediate. Subsequently, water attacks the carbocation to yield a protonated alcohol.
Here, the reaction is regioselective and prefers Markovnikov's addition of water to the alkene. The proton is added to the less substituted end of the double bond, and the -OH group is added to the more substituted carbon on the other end. The reaction is not stereoselective since the water can approach the planar carbocation from both sides, which leads to a racemic mixture of alcohols. Water addition can happen from the same side (syn addition) or the opposite side (anti addition) with respect to the direction from which the proton is added to the double bond. In alkenes with a more substituted carbon adjacent to the double bond, the positive charge in the carbocation intermediate may rearrange (1,2 hydride shift or 1,2 methyl shift) to gain stability. In this situation, a mixture of constitutional isomers of alcohols is formed as products.
An alternative synthetic route for preparing alcohols from alkenes is via oxymercuration-demercuration reaction. In the oxymercuration reaction, the electrophilic mercury in mercury acetate is added to the double bond and forms a three-membered ring structure called mercurinium ion. Water then attacks the mercurinium ion to form organomercurial alcohol. The subsequent step is demercuration, where sodium borohydride replaces the mercury species with hydrogen.
The hydroxyl group bound to the more substituted carbon in the mercurinium ion guides the hydrogen towards the less substituted carbon, eventually resulting in a Markovnikov's product. Also, attack by water is anti with respect to mercury acetate addition. However, the reaction that replaces mercury species with hydrogen is not stereoselective, which results in the formation of both enantiomers of the alcohol as the final product. Due to the absence of a conventional carbocation and its rearrangement, oxymercuration-demercuration has better yields than direct acid-catalyzed hydration.
Anti-Markovnikov's addition of water to an alkene can be performed by the hydroboration-oxidation method. Hydroboration is the single-step addition of a B-H bond from a borane to the two carbons in the double bond via a four-membered transition state. Electrophilic boron attracts the π orbital electrons from the least hindered carbon in the double bond. The resulting partial positive charge is stabilized on the other more substituted carbon atom. Steric factors also favor the addition of boron to the least hindered carbon and hydrogen to the other. The alkyl borane intermediate further reacts with two more alkene molecules to yield a trialkyl borane intermediate. Oxidation of trialkyl borane with hydrogen peroxide in sodium hydroxide replaces the boron with a hydroxyl group. The simultaneous addition of boron and hydrogen from borane ensures a syn addition over the double bond. However, the syn addition can happen from either face of the alkene.
Due to the difference in regiochemistry and reaction mechanisms, these three different synthetic pathways result in different alcohols from the same alkene substrate, as shown in
Figure 1. Addition of water over 3,3-dimethyl-1butene under acid-catalysis (top), oxymercuration-demercuration (middle) and hydroboration-oxidation conditions (bottom).