Reduction oxymercuration

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  

Although this reaction involves two steps, they can be run sequentially in the same flask. This procedure is usually the preferred method for the hydration of an alkene because the yields are higher than the acid-catalyzed addition described in Section 11.3, and rearrangements do not occur. 

Some additional examples are provided by the following equations. Note the excellent yields in all of the examples. Also note that the last example proceeds without rearrangement because the intermediate is a mercurinium ion rather than a carbocation. Attempts to prepare this alcohol by acid-catalyzed addition of water result in completely rearranged product. 

CHAPTER I I ADDITIONS TO CARBON-CARBON DOUBLE AND TRIPLE BONDS 

For simplicity, mercuric acetate is shown with covalent bonds. Mercury has a filled 5d subshell. Two of these 5d unshared electrons are shown. 

The addition reactions discussed in Sections 4.1.1 and 4.1.2 are initiated by the interaction of a proton with the alkene. Electron density is drawn toward the proton and this causes nucleophilic attack on the double bond. The role of the electrophile can also be played by metal cations, and the mercuric ion is the electrophile in several synthetically valuable procedures.13 The most commonly used reagent is mercuric acetate, but the trifluoroacetate, trifluoromethanesulfonate, or nitrate salts are more reactive and preferable in some applications. A general mechanism depicts a mercurinium ion as an intermediate.14 Such species can be detected by physical measurements when alkenes react with mercuric ions in nonnucleophilic solvents.15 The cation may be predominantly bridged or open, depending on the structure of the particular alkene. The addition is completed by attack of a nucleophile at the more-substituted carbon. The nucleophilic capture is usually the rate- and product-controlling step.13,16 

The nucleophiles that are used for synthetic purposes include water, alcohols, carboxylate ions, hydroperoxides, amines, and nitriles. After the addition step is complete, the mercury is usually reductively removed by sodium borohydride, the net result being the addition of hydrogen and the nucleophile to the alkene. The regio-selectivity is excellent and is in the same sense as is observed for proton-initiated additions.17 

Tri-n-butyltin hydride can also be used for reductive demercuration.20 An alternative reagent for demercuration is sodium amalgam in a protic solvent. Here the evidence is that free radicals are not involved and the mercury is replaced with retention of configuration.21 

The stereochemistry of oxymercuration has been examined in a number of systems. Conformationally biased cyclic alkenes such as 4-r-butylcyclohexene and 4-f-butyl-l-methycyclohexene give exclusively the product of anti addition, which is consistent with a mercurinium ion intermediate.17,22 

Electrophilic Additions to Carbon-Carbon Multiple Bonds 

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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. 

OXYMERCURATION-REDUCTION ALCOHOLS FROM OLEFINS 1-METHYLCYCLOHEXANOL, 53, 94... 

Figure 16. Effect of model reactions. the halide in the oxymercuration-reduct ion...

Oxymercuration of 4-/ -butyIcycIohcxcnc, followed by NaBH4 reduction, gives c/.v-4-/-butylcyclohexanol and Ira / , v - 3 - / - b u ty I eye I o h c x a n o I in approximately equal amounts. l-Methyl-4-t-butylcyclohexene irnder similar conditions gives only c/.v-4-/-butyl-1 -methylcyclohexanol. Formulate a mechanism for the oxymercuration-reduction process that is consistent with this stereochemical result. 

Our solution to this synthetic problem was the development of an iterative technique for preparing hydroxypropyl ethers from allyl ethers via oxymercuration-reduction. Figure 3 illustrates the process for the preparation of a series of three chain-extended hydroxypropyl derivatives of 2,6-dimethoxyphenol. Conversion of phenol 1 to the allyl ether 2 under phase-transfer conditions (6) was followed by oxymercuration (7) to give the intermediate organomercurial 3, which was reduced without isolation to give hydroxypropyl ether 4 in 64% overall yield. Ether 4. was then allylated to provide 5, which upon oxymercuration-reduction afforded hydroxypropyl derivative 6. One further iteration of the allylation-oxymercuration-reduction sequence yielded the hydroxypropyl compound 7. 

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. 

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 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. 

Oxidation of an Alcohol- Section 10.14 Figure 10.8 Oxymercuration-Reduction Section 11.6 Figure 11.5 Ozonolysis of an Alkene Section 11.11... 

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. 

Only oxymercuration/reduction can be used to produce an alcohol that has -OH bonded to the more substituted carbon. A third alkene, 2,3-dimethyl-2-pentene, gives a mixture of tertiary alcohols when treated with either BH3 or Hg(OAc)2. 

The Markovnikov product results from oxymercuration/reduction. 

Alcohols can be prepared by hydration of alkenes. Because the dii hydration of alkenes with aqueous acid is generally a poor ruacuoo in the laboratury. tvw> indirect methods are commonly uaed Hydro-borationfmtidation yields the product of sy , r on-Morkovnikov hydr, tion iSection 7.5). whereas oxymercuration/reduction yields the p od-1 urt of Markovnikow hydration (Section 7,4). Both reactions are generally applicable to most alkenes. 

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