Alkenes alkoxymercuration-demercuration

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. ... 

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... 

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. 

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. 

The Williamson Ether Synthesis is not the only ether preparation available, and it is not suitable for sterically crowded ethers. Ethers can also be synthesized by the addition of an alcohol to an alkene. Just as hydration of an alkene gives an alcohol product (water as a nucleophile installs an OH group), addition reactions in the presence of an alcohol gives an ether product (alcohol as a nucleophile installs an OR group). Two examples are shown below the alkene can react initially with either a strong acid or a mercury cation (alkoxymercuration-demercuration). 

If an alcohol (ROH) is used in place of water, then the result is a Markovnikov addition of the alcohol (RO and H) across the alkene. This process is called alkoxymercuration-demercuration, and it can be used as another way of preparing ethers. 

Ethers can be prepared from alkenes via alkoxymercuration-demercuration, which results in a Markovnikov addition of RO and H across an alkene. 

Alkoxymercuration-demercuration converts the alkene into an ether, which is then cleaved into two alkyl halides upon treatment with excess HI ... 

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. 

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. 

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. 

---