Oxymercuration-demercuration of alkenes

The net addition of H—OH to alkenes is cis, anti-Markovnikov, and free from rearrangement. 4. Oxymercuration-Demercuration of Alkenes... 

Acid catalyzed hydration of alkenes is not well suited for laboratory preparation of alcohols. Since the reaction proceeds via carbocation intermediates, mixtures of alcohols may be formed. However, oxymercuration-demercuration of alkenes provides a simple tool for regioselective hydration of alkenes whereby rearrangements are seldom observed. 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

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. 

Step 1 Hydroboration-oxidation of sterically less hindered terminal alkene. Step 2 Oxymercuration-demercuration of the internal alkene yields the diol G. 

Oxymercuration-demercuration of an unsymmetrical alkene generally gives Markovnikov orientation of addition, as shown by the oxymercuration of propene in the preceding example. The mercurinium ion has a considerable amount of positive charge on both of its carbon atoms, but there is more of a positive charge on the more substituted carbon atom, where it is more stable. Attack by water occurs on this more electrophilic carbon, giving Markovnikov orientation. The electrophile, +Hg(OAc), remains... 

Similarly, oxymercuration-demercuration of 3,3-dimethylbut-l-ene gives the Markovnikov product, 3,3-dimethylbutan-2-ol, in excellent yield. Contrast this unrearranged product with the rearranged product formed in the acid-catalyzed hydration of the same alkene in Section 8-4B. Oxymercuration-demercuration reliably adds water across the double bond of an alkene with Markovnikov orientation and without rearrangement. 

The products obtained from the oxymercuration-demercuration of alkenylacetates under standard conditions (NaBH4/NaOH 3 M) are diols. However, the yields are significantly lower than with methoxy-and hydroxy-alkenes because of competitive deoxymercuration.Increasing the amount of base results in major increases in the yield of hydrated products. A less basic procedure has been developed, which allows for the survival of the acetate group. 

In both SnI and Sn2 reactions, the leaving group is the halogen of an alkyl halide or the sulfonate group of a sulfonate ester. Both alkyl halides and sulfonate esters are prepared from alcohols. In Chapter 10, alcohols were prepared by the hydration reaction of alkenes, by oxymercuration-demercuration of alk-enes, or by hydroboration of alkenes. Other methods can be used to prepare alcohols, and they will be discussed at a later time. This section will describe several of the reactions used to convert alcohols to halides or sulfonate esters. 

What products would you expect from oxymercuration-demercuration of the following alkenes ... 

Write the structure of the product of oxymercuration-demercuration of 3,3-dimethyU-butene. Is this product the same as would be obtained by the acid-catalyzed hydration of the alkene ... 

In Chapter 15, we saw that we can convert an alkene to an alcohol by oxymercuration-demercuration. If we perform oxymercuration-demercuration of an alkene in an alcohol as the solvent, the product is an ether. In this reaction, the alcohol, rather than water, acts as the nucleophile. This process, called alkoxymercuration, occurs by a mechanism analogous to oxymercuration. First, electrophihc addition of Hg(OAc)2 to the carbon-carbon double bond forms a mercurinium ion intermediate, which is subsequently attacked by the nucleophilic oxygen atom of the alcohoL... 

Oxymercuration/demercuration provides a milder alternative for the conventional acid-catalyzed hydration of alkenes. The reaction also provides the Markovnikov regiochemistry for unsymmetrical alkenes.33 Interestingly, an enantioselective/inverse phase-transfer catalysis (IPTC) reaction for the Markovnikov hydration of double bonds by an oxymercuration-demercuration reaction with cyclodextrins as catalysts was recently reported.34 Relative to the more common phase-transfer... 

Oxymercuration-demercuration gives Markovnikov addition of H- and -OH to an alkene, yet it is not complicated by rearrangement. 

Application of the oxymercuration-demercuration reaction176 to alkyl 3,4-dideoxy-a-DL-hex-3-enopyranosides provides177 easy access to alkyl 3-deoxyhexopyranosides (for example, 288). Interestingly, both stereoisomeric forms of the alkene are apparently attacked by mercuric acetate from the same side. It has been assumed177 that the transient, mercurinium ion 287 is stabilized by bonding to the 1-meth-oxyl group. 

Mechanism. The reaction is analogous to the addition of bromine molecules to an alkene. The electrophilic mercury of mercuric acetate adds to the double bond, and forms a cyclic mercurinium ion intermediate rather than a planer carbocation. In the next step, water attacks the most substituted carbon of the mercurinium ion to yield the addition product. The hydroxymercurial compound is reduced in situ using NaBH4 to give alcohol. The removal of Hg(OAc) in the second step is called demer-curation. Therefore, the reaction is also known as oxymercuration-demercuration. 

Neutral cyclodextrins have been used as chiral phase-transfer catalysts for an interesting inverse phase-transfer catalysis reaction [50]. The Markovnikovhydration of the double bond by an oxymercuration-demercuration reaction has been demonstrated in the presence of cyclodextrins as chiral phase-transfer catalysts to obtain products in low to moderate enantioselectivity (Scheme 7.16). The mercuric salts are water-soluble, and remain in the aqueous phase, whereas the neutral alkenes prefer an organic phase. A neutral cyclodextrin helps to bring the alkenes into the aqueous phase in a biphasic reaction, and also provides the necessary asymmetric environment. 

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... 

Of the methods we have seen for Markovnikov hydration of alkenes, oxymercuration-demercuration is most commonly used in the laboratory. It gives better yields than direct acid-catalyzed hydration, it avoids the possibility of rearrangements, and it does not involve harsh conditions. There are also disadvantages, however. Organomercurial compounds are highly toxic. They must be used with great care and then must be disposed of properly. 

The two-stage process of oxymercuration-demercuration is fast and convenient, takes place under mild conditions, and gives excellent yields—often over 90%. The alkene is added at room temperature to an aqueous solution of mercuric acetate diluted with the solvent tetrahydrofuran. Reaction is generally complete within minutes. The organomercurial compound is not isolated but is simply reduced in situ by sodium borohydride, NaBH4. (The mercury is recovered as a ball of elemental mercury.)... 

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