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. 

How would you prepare ethyl phenyl ether Use whichever method you think is more appropriate, the Williamson synthesis or the alkoxymercuration reaction. 

Alkene derived compatible with alkoxymercuration method... 

I Review the mechanism of oxymercuration shown in Figure 7.4 (p. 225), and then i write the mechanism of the alkoxymercuration reaction of 1-methylcvclopentene with ethanol. Use curved arrows to show the electron flow in each step. 

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

Furthermore, more recent work about the monoalkoxymercuration of a series of conjugated dienes with different mercury salts has shown157 that the alkoxymercuration of these compounds proceeds in two steps, the first being the formation of 1,2-adducts in which, with the exception of the mercuration of a-terpinene, the alkoxy group occupies the allylic position. The 1,2-alkoxymercurials are in equilibria with the corresponding... 

Glycals, for example D-glucal (23), being vinyl ethers are susceptible to acid catalysed additions of alcohols which result in the formation of 2-deoxyglycosides, but elimination reactions accompany additions of this type 86) go such products are better prepared by way of halogen adducts or by the alkoxymercuration reaction (see below). On the other hand, the addition procedure can be more suitable than the alcoholysis... 

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. ... 

Problem 14.12 Use any needed starting material to synthesize the following ethers, selecting from among intermolecular dehydration, Williamson synthesis, and alkoxymercuration-demercuration. Justify your choice of method. 

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. 

When five- or six-membered ring ethers can readily be formed by intramolecular alkoxymercuration of the initially formed alkenol, cyclic ethers are often the observed product (equation 219).341 This process has recently proven useful in the synthesis of spirocyclic acetals (equation 220).342... 

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. 

One major advantage of the alkoxymercuration-demercuration approach to ethers over the acid-catalyzed process is the fact that carbon skeleton rearrangements are seldom observed. Only unsaturated cyclopropanes,42S>426 or aryl-substituted alkenes427 428 in the presence of highly electrophilic mercury salts afford rearranged products. 

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. 

Considerable work on the alkoxymercuration of allenes has been reported.413 Mono- or di-mercuration products are observed depending on the substitution pattern of the allene. While allene and 1,2-butadiene afford dimercurated acetals, more highly substituted allenes produce vinylmercurials (equations 266 and 267).448 Cyclic allenes also afford vinylmercurials.449 450 Alkaline sodium borohydride reduction of these vinylmercurials produces the expected allylic ethers. 

The alkoxymercuration of conjugated dienols does not appear to have been examined, while allenic alcohols provide unsaturated ethers (equation 269)452 The alkoxymercuration of alkynes generally provides vinylic ethers453 or acetals454 depending on the reaction conditions (equations 270 and 271). Only catalytic amounts of mercuiy salts are generally... 

A study of the intramolecular alkoxymercuration of ( )-5-arylpent-4-en-l-ols (70) has indicated that the regioselectivity is closely related to the Hammett constants of the para-substituents on the benzene ring. Large solvent effects on the regioselectivity were also observed (Scheme 17 and Tables 2 and 3). By contrast, the related oxymercuration of -methylstyrene is 100% a-sclcctivc. This comparison shows that the regioselectivity of the intermolecular reaction is controlled by electronic factors, whereas the cyclization is governed by a delicate balance of steric and electronic effects.65... 

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