Alkoxymercuration of Alkenes

The mechanism of the alkoxymercuration reaction is similar to that described in Section 7.4 for hydroxymercuration. The reaction is initiated by electrophilic addition of to the alkene, followed by reaction of the 

A wide variety of alcohols and alkenes can be used in the alkoxymercu-ration reaction. Primary, secondaiy, and even tertiary alcohols react smoothly, but ditertiaiy ethers can t be prepared because of steric hindrance to reaction. 

How would you prepare ethyl phenyl ether Use whichever method you think is more appropriate, the Williamson symthesis or the alkoxymercu-ration reaction. 

Draw the target ether, identify the two groups attached to oxygen, and recall the limitations of the two methods for preparing ethers. The Williamson synthesis uses an Sn2 reaction and requires that one of the two groups attached to oxygen be either secondary or (preferably) primary. The alkoxymercura-tion reaction requires that one of the two groups come from an alkene pis-cursor. Ethyl phenyl ether could be made by either method. 

I riinary carbon compatible-with William.son methofl 

We saw in Section 7.4 that alkenes react with water in the presence of mercuric acetate to yield a hydroxymercuration product. Subsequent treatment with NaBH4 breaks the C-Hg bond and yields the alcohol. A similar alkoxymercuration reaction occurs when an alkene is treated with an alcohol in the presence of mercuric acetate. (Mercuric trifluoroacetate, (CF3C02 4Hg, works even better.) Demercuration by reaction with NaBH4 then yields an ether. As indicated by the following examples, the net result is Markovnikov addition of the alcohol to the alkene. 

Primary carbon compatible with Williamson method 

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Electrophilic Addition to Alkenes, Hydroxy- and alkoxymercurations of alkenes have been performed in micellar SDS. Hydroxymercuration of (1) with mercury(II) acetate, followed by reduction with sodium borohydride, gave a greatly enhanced yield of (2) in micellar SDS (90%) relative to that obtained in THF-H2O (20-25%) (eq 2). Also, the reactions of (1) and the related limonene gave greater cyclic ether diol product ratios in the SDS environment than in aq THF. Both the enhanced 3delds and ratios were attributed to anisotropic solubilization of the alkylmercurial intermediate in a relatively H2O poor mIceUar microenvironment. The hydroxymercuration of an aromatic diene, /Mliallylbenzene, did not display enhanced chemoselectivlty (mono vs. diol formation) in micellar SDS relative to that obtained in THF-H2O. This result suggests that the mIceUar solubilization sites of aromatic substrates and reaction intermediates are more HzO-rich than those of aliphatic systems. 

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... 

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... 

Alkoxymercurations are performed using Hg(OAc)2 in the alcohol as solvent Methanol is used most frequently, and its reactions with an array of alkenes are known ... 

Alkoxymercuration of 1-octene In micellar SDS by added primary alcohols gave 2-oclyl alkyl ethers. Thus when a given alcohol cannot be employed as both the reactant and solvent In the alkoxymercuration of an alkene, the use of micellar SDS-alcohol could be an attractive option. 

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. 

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

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). 

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. 

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. 

Ethers are prepared either by a Williamson synthesis or by alkoxymercuration/demercuration sequence. The Williamson ether sy thesis involves S -2 attack of an alkoxide ion on a primary alkyl halide. The alkoxymercuration reaction involves the formation of an intermediate organomercury compound, followed by NaBH4 reduction of the C-Hg bond. The net result is Markovnikov addition of an alcohol to an alkene. 

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