Addition reactions oxymercuration-demercuration

When predicting the product of a reaction, you have to recall what you know about the kind of reaction being carried out and then apply that knowledge to the specific case you re dealing with. In the present instance, recall that the two methods of hydration— hydroboratlon-oxidation and oxymercuration-demercuration—give complementary products. Hydroboration-oxidation occurs with syn stereochemistry and gives the non-Markovnikov addition product oxymercuration-demercuration gives the Markovnikov product. 

Oxymercuration-demercuration is a useful laboratory method for the synthesis of small quantities of alcohol. Like the catalytic hydration reaction, this process is an example of Markovnikov addition. It s a useful procedure because it tends to result in high yields and rearrangements rarely occur. 

Mechanism. The reaction is analogous to the addition of bromine molecules to an alkene. The electrophilic mercury of mercuric acetate adds to the double bond, and forms a cyclic mercurinium ion intermediate rather than a planer carbocation. In the next step, water attacks the most substituted carbon of the mercurinium ion to yield the addition product. The hydroxymercurial compound is reduced in situ using NaBH4 to give alcohol. The removal of Hg(OAc) in the second step is called demer-curation. Therefore, the reaction is also known as oxymercuration-demercuration. 

In the oxymercuration process, the electrophilic addition of the mercuric species occurs resulting in a mercurinium ion which is a three-membered ring. This is followed by the nucleophilic attack of water and as the proton leaves, an organomercuric alcohol (addition product) is formed. The next step, demercuration, occurs when sodium borohydride (NaBH ) substitutes the mercuric acetate substituent with hydrogen. If an alkene is unsymmetric, Oxymercuration-demercuration results in Markovnikov addition. The addition of mercuric species and water follows an anti (opposite side) addition pattern. This reaction has good yield, since there is no possibility of rearrangement unlike acid-catalyzed hydration of alkenes. 

Formation of the secondary alcohol 71 clearly indicates that reaction of the alkene and the Lewis acid gives the more stable secondary carbocation. Indeed, this is the mechanism for this transformation, as discussed in further detail later. The overall transformation is a hydration process that adds water to the more substituted carbon of the alkene (sometimes called a Markovnikov addition), followed by removal of mercury, and is called oxymercuration-demercuration or simply oxymercuration. 

Addition reactions that will produce alcohols include acid-catalyzed hydration, oxymercuration-demercuration, and hydroboration-oxidation. 

In the laboratory, alkenes are often hydrated by the oxymercuration-demercuration procedure. Oxymercuration involves electrophilic addition of Hg2+ to the alkene on reaction with mercury(II) acetate [(CH3C02)2Hg, often abbreviated Hg(OAc)2] in aqueous tetrahydrofuran (THF) solvent. When the intermediate organomercury compound is then treated with sodium borohydride, NaBH4, demercuration occurs to produce an alcohol. For example ... 

In addition to the oxymercuration-demercuration method, which yields the Markovnikov product, a complementary method that yields the non-Markovnikov product is also useful. Discovered in 1959 by H.C. Brown and called hydroboration, the reaction involves addition of a B-H bond of borane, BH3, to an alkene to yield an organoborane intermediate, RBH2. Oxidation of the organoborane by reaction with basic hydrogen peroxide, H2O2, then gives an alcohol. For example ... 

One of the features that makes the hydroboration reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration-oxidation of 1-methylcyclopentene yields trans-2-methylcyclopentanol. Boron and hydrogen add to the alkene from the same face of the double bond—that is, with syn stereochemistry, the opposite of anti— with boron attaching to the less highly substituted carbon. During the oxidation step, the boron is replaced by an OH with the same stereochemistry, resulting in an overall syn non-Markovnikov addition of water. This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration-demercuration. 

The last example in Table 12-2 is an electrophilic addition of a mercuric salt to an alkene. The reaction is called mercuration, and the resulting compound is an alkyl-mercury derivative, from which the mercury can be removed in a subsequent step. One particularly useful reaction sequence is oxymercuration-demercuration, in which mercuric acetate acts as the reagent. In the first step (oxymercuration), treatment of an alkene with this species in the presence of water leads to the corresponding addition product. 

In an oxymercuration-demercuration reaction, an alkene is treated with mercury(II) acetate, Hg(OAc)2, and the product is treated with sodium borohydride. The net result is a Markovnikov addition product in which the OH group bonds to the more substituted carbon atom of the alkene. 

In Chapter 15, we saw that we can convert an alkene to an alcohol by oxymercuration-demercuration. If we perform oxymercuration-demercuration of an alkene in an alcohol as the solvent, the product is an ether. In this reaction, the alcohol, rather than water, acts as the nucleophile. This process, called alkoxymercuration, occurs by a mechanism analogous to oxymercuration. First, electrophihc addition of Hg(OAc)2 to the carbon-carbon double bond forms a mercurinium ion intermediate, which is subsequently attacked by the nucleophilic oxygen atom of the alcohoL... 

Students confuse oxymercuration-demercuration (Synthetic Transformation 1) with anti-Markovnikov addition of H and OH (S5mthetic Transformation 8.3), perhaps because they both result in delivery of an H and OH to an alkene (though to different carbons ) or because they both involve boron (but in different steps for different purposes). It is worth your time to put the note cards with these reactions side by side and figure out the differences. 

Addition of alcohol to alkenes hy alkoxymercuration-reduction produces ethers via Markovnikov addition. This addition is similar to the acid-catalysed addition of an alcohol. For example, propene reacts with mercuric acetate in aqueous THF, followed hy reduction with NaBFl4, to yield methyl propyl ether. The second step is known as demercuration, where Flg(OAc) is removed hy NaBH4. Therefore, this reaction is also called alkoxymercura-tion-demercuration. The reaction mechanism is exactly the same as the oxymercuration-reduction of alkenes. 

The first stage, oxymercuration, involves addition to the carbon-carbon double bond of —OH and —HgOAc. Then, in demercuration, the —HgOAc is replaced by —H. The reaction sequence amounts to hydration of the alkene, but is much more widely applicable than direct hydration. 

---