Alkoxymercuration-reduction

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. 

We have seen that alkenes react with alcohols in the presence of an acid catalyst to form ethers (Section 4.5). Just as the addition of water works better in the presence of mercuric acetate than in the presence of a strong acid, the addition of an alcohol works better in the presence of mercuric acetate. [Mercuric trifluoroacetate, Hg(02CCp3)2, works even better.] This reaction is called alkoxymercuration-reduction. 

The mechanisms for oxymercuration and alkoxymercuration are essentially identical the only difference is that water is the nucleophile in oxymercuration and an alcohol is the nucleophile in alkoxymercuration. Therefore, the product of oxymercuration-reduction is an alcohol, whereas the product of alkoxymercuration-reduction is an ether. 

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. 

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. 

Addition of mercury and an alkoxy group to a double bond, usually by a solution of mercuric acetate in an alcohol. Alkoxymercuration is usually followed by sodium borohydride reduction (demercuration) to give an ether, (p. 636)... 

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. 

Oxymercuration, alkoxymercuration, and the addition of Br2 and CI2 form cyclic intermediates. Oxymercuration and alkoxymercuration are followed by a reduction reaction. Reduction increases the number of C — H bonds or decreases the number of C — O, C—N, or C—X bonds (where X denotes a halogen). Hydroboration is followed by an oxidation reaction. Oxidation decreases the number of C—H bonds or increases the number of C—O, C—N, or C—X bonds (where, again, X denotes a halogen). 

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. 

Alkoxymercuration of acylaminoacrylic acids followed by NaBILi-reduction affords a-alkoxy-a-acylaminopropionic acids 139). 

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