Alkene alkoxymercuration

We saw in Section 7.4 that alkenes react with water in the presence of mercuric acetate to yield a hvdroxymercuration product. Subsequent treatment with NaBH4 breaks the C-Hg bond and yields the alcohol. A similar alkoxymercuration reaction occurs when an alkenc is treated with an alcohol in the presence of mercuric acetate or, even better, mercuric trifluoroacetate, (Cl CCtitiHg. Demercura-tion by reaction with NaBH4 then yields an ether. The net result is Markovnikov addition of the alcohol to the alkene. 

The mechanism of the alkoxymercuration reaction is similar to that described in Section 7.4 for hvdroxymercuration. The reaction is initiated by electrophilic addition of Iig2+ to the alkene, followed by reaction of the intermediate cation with alcohol and reduction of the C-Hg bond by NaBH4. A variety of alcohols and alkenes can be used in the alkoxymercuration reaction. Primary, secondary, and even tertiary alcohols react well, but ditertiary ethers can t be prepared because of steric hindrance to reaction. 

Alkene derived compatible with alkoxymercuration method... 

Alkoxymercuration reaction (Section 18.2) A method for synthesizing ethers by mercuric-ion catalyzed addition of an alcohol to an alkene. 

Problem 14.6 Give the alkene and alcohol needed to prepare the following ethers by alkoxymercuration-demercuration (a) diisopropyl ether, (b) 1-methyl-l-methoxycyclopentane, (c) 1-phenyl-1-ethoxypropane, (d) di-f-butyl ether. ... 

Ethers are prepared from alkyl halides by the treatment of metal alkoxide. This is known as Williamson ether synthesis (see Sections 4.3.6 and 5.5.2). Williamson ether synthesis is an important laboratory method for the preparation of both symmetrical and unsymmetrical ethers. Symmetrical ethers are prepared by dehydration of two molecules of primary alcohols and H2SO4 (see Sections 4.3.7 and 5.5.3). Ethers are also obtained from alkenes either by acid-catalysed addition of alcohols or alkoxymercuration-reduction (see Section 5.3.1). 

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 alkoxymercuration-demercuration of alkenes, dienes and alkynes in the presence of alcohols provides an even more versatile approach to the corresponding ethers than the acid-catalyzed process. This reaction has been extensively studied and thoroughly reviewed recently.415 The reaction of alkenes is best carried out using meicury(II) acetate or, for more highly substituted alcohols or alkenes, mercury(II) trifluoroacetate (equation 257).416,417... 

A wide variety of alcohols and alkenes can be utilized in this process. Numerous functional groups in either the alcohol or the alkene can be accommodated during alkoxymercuration. For example, alkenes differing in their nucleophilicity as much as vinylic ethers419 and a,(3-unsaturated aldehydes or ketones420,421 react smoothly (equations 259 and 260). 

The stereochemistry of addition to acyclic, cyclic and polycyclic alkenes is essentially identical to that of hydroxymercuration wherever the two processes have been compared. Fewer data have been accumulated for alkoxymercuration however. 

The kinetics of alkoxymercuration have received considerable attention 415 The relative reactivity of various alkenes parallels that reported for hydroxymercuration. 

The alkoxymercuration of dienes and polyenes has been extensively studied. Mono-, di- or poly-mer-curated adducts are formed as expected based on results from the alkoxymercuration of analogous alkenes, but the product distribution varies depending on the nature of the diene or polyene. 

The alkoxymercuration of conjugated dienes is more complex since these compounds are less reactive than simple alkenes and the products often react further to afford dimercurated products whose regio- or stereo-chemistry is strongly affected by the initial product. For example, 1,3-butadiene, 1,3-pentadiene, 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene react with meicuiy(II) acetate in methanol to produce 1,2-adducts (equation 265).443-446 These adducts sometimes rearrange with time.446 1,3-Butadiene reacts further to afford primarily the meso adduct of double 1,2-additions.447 Surprisingly, little additional work has been reported on reactions of conjugated dienes. 

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... 

When mercuration takes place in an alcohol solvent, the alcohol serves as a nucleophile to attack the mercurinium ion. The resulting product contains an alkoxy (—O—R) group. In effect, alkoxymercuration-demercuration converts alkenes to ethers by adding an alcohol across the double bond of the alkene. 

The alkoxymercuration-demercuration process adds a molecule of an alcohol across the double bond of an alkene (Section 8-6). The product is an ether, as shown here. 

The reaction mechanism of alkoxymercuration/demercuration of an alkene is similar to other electrophilic additions we have studied. First, the cyclopentene n electrons attack Hg2+ with formation of a mercurinium ion. Next, the nucleophilic alcohol displaces mercury. Markovnikov addition occurs because the carbon bearing the methyl group is better able to stabilize the partial positive charge arising from cleavage of the carbon-mercury bond. The ethoxyl and mercuric groups are trans to each other. Finally, removal of mercury by NaBH4 by a mechanism that is not fully understood results in the formation of 1-ethoxy-1-methylcyclopentane. 

Thus good yields of p-alkoxy alcdiols can be obtained, albeit as diastereomeric mixtures, but unfortunately hydtoxymercurated alkenes unda similar conditions do not lead to useful products. Despite this iqrparent limitation, alkoxymercuration-oxidative demercuration has been very effective in a number of systems described below, and there is no doubt it is a procedure worth consi ration for hydroxy group introduction. 

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