Addition of Water to Alkenes Oxymercuration

Acid-catalyzed alkene hydration is particularly suited to large-scale industrial procedures, and approximately 300,000 tons of ethanol are manufactured each year in the United States by hydration of ethylene. The reaction is of little value in the typical laboratory, however, because it requires high temperatures— 250 °C in the case of ethylene—and strongly acidic conditions. 

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. 

Q A hydrogen atom on the electrophile HgO is attacked by r. electrons from the nucieophiiic double bond, forming a new C-H bond. This leaves fhe other carbon atom with a + charge and a vacant p orbital. Simultaneously, two electrons from the H-O bond move onto oxygen, giving neutral water. 

Acid-catalyzed hydration of isolated double bonds is also uncommon in biological pathways. More frequently, biological hydrations require that the double bond be adjacent to a carbonyl group for reaction to proceed. Fumarate, for instance, is hydrated to give malate as one step in the citric acid cycle of food metabolism. Note that the requirement for an adjacent carbonyl group in the addition of water is the same as that we saw in Section 7.1 for the elimination of water. We ll see the reason for the requirement in Section 19.13, but might note for now that the reaction is not an electrophilic addition but instead occurs 

Thomsonl Click Organic Interactive to use a web-based palette to predict products of the oxymercuration of alkenes. 

0 Water acts as a base to remove H , regenerating H30 and yielding the neutral alcohol addition product. 

In the laboratory, alkenes are often hydrated by the oxymercura-tion procedure. When an alkene is treated with mercurydl) acetate [Hg(02CCH3)2, usually abbreviated HgOAclal in aqueous tetrahydrofuran (THF) solvent, electrophilic addition to the double bond rapidly occurs. The intermediate organomercury compound is then treated with sodium boro-hydride, NaBH4, and an alcohol is produced. For example  

Reaction of an alkene with acid (HA) yields a carbocation intermediate. 

Water acts as a nucleophile, using a lone pair of electrons on oxygen to form a bond to carbon. The oxygen atom, having donated electrons, is now trivalent and has the positive charge. 

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Addition of Water to Alkenes Oxymercuration 239 Addition of Water to Alkenes Hydroboration 242 Addition of Carbenes to Alkenes Cyclopropane Synthesis Reduction of Alkenes Hydrogenation 249... 

Oxymercuration-reduction of alkenes preparation of alcohols Addition of water to alkenes by oxymercuration-reduction produces alcohols via Markovnikov addition. This addition is similar to the acid-catalysed addition of water. Oxymercuration is regiospecific and auft -stereospecific. In the addition reaction, Hg(OAc) bonds to the less substituted carbon, and the OH to the more substituted carbon of the double bond. For example, propene reacts with mercuric acetate in the presence of an aqueous THF to give a hydroxy-mercurial compound, followed by reduction with sodium borohydride (NaBH4) to yield 2-propanol. 

The addition of water to alkenes, to produce alcohols, requires the presence of either (i) a strong acid or (ii) mercury(II) acetate (in an oxymercuration reaction). In both cases, the reactions involve the Markovnikov addition of water (i.e. the OH becomes attached to the more substituted carbon). 

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. 

STRATEGY AND ANSWER We recognize that synthesis by path (a) would require a Markovnikov addition of water to the alkene. So, we could use either acid-catalyzed hydration or oxymercuration—demercuration. 

The addition of an acid such as HX to an alkene leads to formation of an alkyl halide. If the acid catalyzed addition of water or an alcohol is examined, the product is an alcohol or an ether. Oxymercuration also leads to addition of water to an alkene. The functional group exchange can be generalized as shown, where X = Cl, Br, I, OH, OR. When an alkene reacts with a halogen, the product is a vicinal dihalide. The functional group exchange is shown where X = Cl, Br, I. When bromine in water or chlorine in water is reacted with an... 

One of the features that makes the hydrobora ( ion reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration/oxidation of 1-methylcyclopentene yields trans-2-methylcydopentanol. Boron and hydrogen both 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. 

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. 

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 mechanism of the mercurydD-catalyzed alkyne hydration reactioi is analogous to the oxymercuration reaction of alkenes (Section 7.4). Elec trophilic addition of mercury(II) ion to the alkyne gives a vinylic cation which reacts with water and loses a proton to yield a mercury-containii enol intermediate. In contrast to alkene oxymercuration, no treatment widi NaBH4 is necessary to remove the mercury the acidic reaction conditions alone are sufficient to effect replacement of mercury by hydrogen (Figure 8.3). 

The mercuric ion-catalyzed hydration of alkynes probably proceeds in a similar manner to the oxymercuration of alkenes (see Section 5.1). Electrophilic addition of Hg to the triple bond leads to a vinylic cation, which is trapped by water to give an vinylic organomercury intermediate. Unlike the alkene oxymercuration, which requires reductive removal of the mercury by NaBH4, the vinylic mercury intermediate is cleaved under the acidic reaction conditions to give the enol, which tautomerizes to the ketone. Hydration of terminal alkynes follows the Mai kovnikov rule to furnish methyl ketones. ° ... 

In Section 4.5, you learned that water adds to an alkene if an acid catalyst is present. This is the way aUcenes are converted into alcohols industrially. However, under normal laboratory conditions, water is added to an alkene by a procedure known as oxymercuration-reduction. The addition of water by oxymercuration-reduction has two advantages over acid-catalyzed addition It does not require acidic conditions that are harmful to many organic molecules, and because carbocation intermediates are not formed, carbocation rearrangements do not occur. 

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