Hydration oxymercuration

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

Three of the six reactions are well suited for the synthesis of alcohols acid-catalyzed hydration, oxymercuration (after reduction of the C-Hg bond by NaBHi), and hydroboration (by oxidation of the C-B bond by H2O2). Compare the alcohol from hydration (shown earlier) with that from demer-curation of the oxymercuration product ... 

Methyl ketones are important intermediates for the synthesis of methyl alkyl carbinols, annulation reagents, and cyclic compounds. A common synthetic method for the preparation of methyl ketones is the alkylation of acetone derivatives, but the method suffers limitations such as low yields and lack of regioselectivity. Preparation of methyl ketones from olefins and acetylenes using mercury compounds is a better method. For example, hydration of terminal acetylenes using HgSO gives methyl ketones cleanly. Oxymercuration of 1-olefins and subsequent oxidation with chromic oxide is... 

Vn. Oxymercuration A Convenient Route to Markovnikov Hydration of Olefins... 

In the laboratory, alkenes are often hydrated by the oxymercuration procedure. When an alkene is treated with mercury(II) acetate Hg(02CCH3)2, usually abbreviated Hg(OAc)2l in aqueous tetrahydrofuran (THF) solvent, electrophilic addition of Hg2+ to the double bond rapidly occurs. The intermediate orgnnomercury compound is then treated with sodium borohydride, NaBH4, and an alcohol is produced. For example ... 

Hydration of an alkene—the addition of water—is carried out by either of two procedures, depending on the product desired. Oxymercuration involves electrophilic addition of Hg2+ to an alkene, followed by trapping of the cation intermediate with water and subsequent treatment with NaBH4. Hydroboration involves addition of borane (BH3) followed by oxidation of the intermediate organoborane with alkaline H202- The two hydration methods are complementary oxymercuration gives the product of Markovnikov addition, whereas hydroboration/oxidation gives the product with non-Markovnikov syn stereochemistry. 

Draw the structures of alkenes that would yield the following alcohols on hydration (red - O). Tell in each case whether you would use hydroboration/ oxidation or oxymercuration. 

Oxymercuration (Section 7.4) A method for double-bond hydration using aqueous mercuric acetate as the reagent. 

Alkenes can be hydrated quickly under mild conditions in high yields without rearrangement products by the use of oxymercuration (addition of oxygen and... 

Moreover, because of the involvement of cationic intermediates, rearrangements can occur in systems in which a more stable cation can result by aryl, alkyl, or hydrogen migration. Oxymercuration-reduction, a much milder and more general procedure for alkene hydration, is discussed in the next section. 

The stereochemical outcome is replacement of the C—B bond by a C—O bond with retention of configuration. In combination with stereospecific syn hydroboration, this allows the structure and stereochemistry of the alcohols to be predicted with confidence. The preference for hydroboration at the least-substituted carbon of a double bond results in the alcohol being formed with regiochemistry that is complementary to that observed by direct hydration or oxymercuration, that is, anti-Markovnikov. 

Oxymercuration/demercuration provides a milder alternative for the conventional acid-catalyzed hydration of alkenes. The reaction also provides the Markovnikov regiochemistry for unsymmetrical alkenes.33 Interestingly, an enantioselective/inverse phase-transfer catalysis (IPTC) reaction for the Markovnikov hydration of double bonds by an oxymercuration-demercuration reaction with cyclodextrins as catalysts was recently reported.34 Relative to the more common phase-transfer... 

Two complementary orientations for the addition of water to a double bond 1) Acid-catalyzed hydration (or oxymercuration-demercuration) of 1-hexene ... 

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. 

Various allylic amines and protected allylic alcohols were tested using different cyclodextrins. Although only low to moderate enantioselectivity was obtained, the method demonstrated for the first time an enantioselective inverse phase-transfer catalysis hydration reaction via an oxymercuration-demercuration process. 

Both, hydration and hydroalkoxylation of olefins are usually carried out under acid catalysis or by oxymercuration reactions, although reactions mediated by palladium or by other metals have recently begun to emerge. In the latter case, nucleophilic addition of the O—H group is favored by a cationic palladium species that activates... 

In addition to the hydration reaction described in Section 11.3, the oxymercuration-reduction reaction can be used to add the elements of water to a carbon-carbon double bond in a two-step process. First the alkene is reacted with mercuric acetate, Hg(02CCH3)2, in water, followed by treatment with sodium borohydride in sodium hydroxide solution ... 

The hydroxy group must be located on one of the doubly bonded carbons of the original alkene, so first draw all of the alkenes that meet this criterion. Examine the alkenes to determine whether it is possible to selectively add the OH group to the desired carbon. Remember that we can add the OH with either Markovnikov orientation (acid-catalyzed hydration or oxymercuration-reduction) or anti-Markovnikov orientation (hydroboration-oxidation), but we will have difficulty selecting between two carbons that are similarly substituted. 

It is possible to regiospecifically add the hydroxy group to carbon 2 of 1-hexene by using either the oxymercuration reaction or acid-catalyzed hydration. However, it is not possible to selectively add a hydroxy group only to carbon 2 of 2-hexene because both carbons are monosubstituted. Therefore, the path starting from 1-hexene should be used. 

Mechanism 8-4 Acid-Catalyzed Hydration of an Alkene 338 8-5 Hydration by Oxymercuration-Demercuration 340 Mechanism 8-5 Oxymercuration of an Alkene 340 8-6 Alkoxymercuration-Demercuration 342 8-7 Hydroboration of Alkenes 343... 

Oxymercuration-demercuration is another method for converting alkenes to alcohols with Markovnikov orientation. Oxymercuration-demercuration works with many alkenes that do not easily undergo direct hydration, and it takes place under milder conditions. No free carbocation is formed, so there is no opportunity for rearrangements or polymerization. 

Similarly, oxymercuration-demercuration of 3,3-dimethylbut-l-ene gives the Markovnikov product, 3,3-dimethylbutan-2-ol, in excellent yield. Contrast this unrearranged product with the rearranged product formed in the acid-catalyzed hydration of the same alkene in Section 8-4B. Oxymercuration-demercuration reliably adds water across the double bond of an alkene with Markovnikov orientation and without rearrangement. 

Of the methods we have seen for Markovnikov hydration of alkenes, oxymercuration-demercuration is most commonly used in the laboratory. It gives better yields than direct acid-catalyzed hydration, it avoids the possibility of rearrangements, and it does not involve harsh conditions. There are also disadvantages, however. Organomercurial compounds are highly toxic. They must be used with great care and then must be disposed of properly. 

Hydration of alkynes (via oxymercuration) gives good yields of single compounds only with symmetrical or terminal alkynes. Show what the products would be from hydration of each compound. 

CHAPTER 8 Ionic Addition of HX to an Alkene 332 Free-Radical Addition of HBr to Alkenes 334 Acid-Catalyzed Hydration of an Alkene 338 Oxymercuration of an Alkene 340 Hydroboration of an Alkene 345 Addition of Halogens to Alkenes 350 Formation of Halohydrins 352 Epoxidation of Alkenes 360 Acid-Catalyzed Opening of Epoxides 362 Olefin Metathesis 376... 

Oxymercuration works particularly well with alkynes. Here are the conditions, and the product, following the analogy of alkene hydration, should be the compound shown at the right-hand end of the scheme below. 

The overall result of the hydroboration-oxidation sequence is addition of water to an alkene with the opposite regiochemistry to that expected for a conventional acid-catalysed hydration. The usual way to do such a hydration is by oxymercuration-reduction. 

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