Oxymercuration — demercuration

In an oxymercuration-demercuration reaction, an alkene is treated with mercury(II) acetate, Hg(OAc)2, and the product is treated with sodium borohydride. The net result is a Markovnikov addition product in which the OH group bonds to the more substituted carbon atom of the alkene. 

In the first step, an electrophilic HgOAc ion adds to the double bond to give a mercurinium ion whose structure is similar to that of a bromonium ion (Section 6.5). Like the bromonium ion, the mercurinium ion is a hybrid of three contributing resonance structures. 

Why does Markovnikov addition occur as a result of the attack of water on the mercurinium ion If the alkene is not symmetric, then neither is the mercurinium ion. In the most important resonance contributor to the ion, the mercury atom has the positive charge. Of the other two contributors, the one with the charge on the more substituted carbon atom is more stable. That is, resonance structure II is more stable than structure III. 

The structure of the transition state for nucleophilic attack of water on the mercurinium ion is closely related to the structure of this intermediate. Thus, the energy barrier is lower for attack of water at the more positive carbon atom of the intermediate. For a mercurinium ion of a terminal monosubstituted alkene such as 1-hexene, attack occurs at C-2, the more substituted site. 

The organomercury compound is reduced with sodium borohydride, and the HgOAc group is replaced by a hydrogen atom. The mechanism is not well established, but is thought to involve free radicals. Thus, the reaction is not necessarily stereospecific. Only the location of the hydroxyl group can be predicted from knowledge of the formation of the mercurinium ion and the ditection of attack of water on that ion. 

Alkenes can be converted into alcohols by oxymercuration-demercura-tion. The addition of H and OH is in accordance with the Markovnikov s rule. There is no rearrangement of the intermediates in this process. 

In the oxymercuration process, the electrophilic addition of the mercuric species occurs resulting in a mercurinium ion which is a three-membered ring. This is followed by the nucleophilic attack of water and as the proton leaves, an organomercuric alcohol (addition product) is formed. The next step, demercuration, occurs when sodium borohydride (NaBH ) substitutes the mercuric acetate substituent with hydrogen. If an alkene is unsymmetric, Oxymercuration-demercuration results in Markovnikov addition. The addition of mercuric species and water follows an anti (opposite side) addition pattern. This reaction has good yield, since there is no possibility of rearrangement unlike acid-catalyzed hydration of alkenes. 

In cases where protonation of the alkene ultimately leads to carbocation rearrangements, acid-catalyzed hydration is an inefficient method for adding water across the alkene. Many other methods can achieve a Markovnikov addition of water across an alkene without carbocation rearrangements. One of the oldest and perhaps best known methods is called oxymercuration-demercuration  

As mentioned in Chapter 2, we generally avoid breaking single bonds when drawing resonance structures. However, this is one of the rare exceptions. We will see one other such exception in the next section of this chapter. 

To understand this process, we must explore the reagents employed. The process begins when mercuric acetate, Hg(OAc)2, dissociates to form a mercuric cation  

This mercuric cation is a powerful electrophile and is subject to attack by a nucleophile, such as the 7t bond of an alkene. When a tt bond attacks a mercuric cation, the namre of the resulting intermediate is quite different from the nature of the intermediate formed when a Tt bond is simply protonated. Let s compare  

When a tt bond is protonated, the intermediate formed is simply a carbocation, as we have seen many times in this chapter. In contrast, when a it bond attacks a mercuric cation, the resulting intermediate cannot be considered as a carbocation, because the mercury atom has electrons that can interact with the nearby positive charge to form a bridge. This intermediate, called a mercurinium ion, is more adequately described as a hybrid of two resonance structures. A mercurinium ion has some of the character of a carbocation, but it also has some of the character of a bridged, three-membered ring. This dual character can be illustrated with the following drawing  

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Ammonia can be added to double bonds (even ordinary double bonds) in an indirect manner by the use of hydroboration (15-16) followed by treatment with NH2CI or NH2OSO2OH (12-29). This produces a primary amine with anti-Markovnikov orientation. An indirect way of adding a primary or secondary amine to a double bond consists of aminomercuration followed by reduction (see 15-3 for the analogous oxymercuration-demercuration procedure), for example. 

On the basis of the mechanistic pattern for oxymercuration-demercuration, predict the structure and stereochemistry of the alcohol(s) to be expected by application of the reaction to each of the following substituted cyclohexenes. 

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 allows the Markovnikov addition of H-and -OH without rearrangements. 

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

Alcohols from Alkenes through Oxymercuration-Demercuration... 

Rearrangements of the carbon skeleton seldom occur in oxymercuration-demercuration. 

Two complementary orientations for the addition of water to a double bond 1) Acid-catalyzed hydration (or oxymercuration-demercuration) of 1-hexene ... 

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... 

Oxymercuration-demercuration is a useful laboratory method for the synthesis of small quantities of alcohol. Like the catalytic hydration reaction, this process is an example of Markovnikov addition. It s a useful procedure because it tends to result in high yields and rearrangements rarely occur. 

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. 

A synthetic neuraminic acid derivative having a methyl ether group at 0-4 (Neu5Ac4Me) was synthesized by Beau and coworkers101,102 by using an oxymercuration-demercuration reaction.103 The metabolic behavior of this compound will be described in Sections V and VI. 

Problem 13.43 Write the structural formulas for the alcohols formed by oxymercuration-demercuration from... 

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. 

Cyclopropane rings can undergo the oxymercuration/ demercuration reaction H... 

Silver(I) catalyzed cyclizations of allenic alcohols (202) lead to 2,5-dihydrofurans (203) (79S743), whilst another mild method for the synthesis of tetrahydrofurans is the intramolecular oxymercuration-demercuration process. Geraniol, when treated with mer-cury(II) acetate and subsequently with sodium borohydride, gave a tetrahydrofuran. 

Complicating side reactions may occasionally occur - as in the oxymercuration-demercuration of styrene to 1-phenylethanol for which experimental details are also given. In this case evidently some organomercurial compounds survive the reductive stage, and their subsequent decomposition during final distillation complicates the isolation of the pure product. 

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