Mercuration-demercuration, of alkene

Whereas mercuration-demercuration of alkenes in the presence of water gives alcohols, in alcohol solvents (free from H,0) ethers result. These reactions in the presence of nucleophilic solvents such as water and alcohols are examples of solvomercuration. The mercuric salts usually used are the acetate, Hg(OAc), (—OAc is an abbreviation for —OCCH,) or the trifluoracetate. Hg(OCOCF,),. ... 

Mercury(II) trifluoroacetate is a good electrophile that is highly reactive toward carbon-carbon double bonds [52, 53, 54 When reacting with olefins in nucleophilic solvents, it usually gives exclusively mercurated solvoadducts, but never products of skeletal rearrangement Solvomercuration-demercuration of alkenes with mercury(II) trifluoroacetate is a remarkably effective procedure for the preparation of esters and alcohols with Markovnikov s regiochemistry [52, 55] (equation 24)... 

In 1978, Corey reported a general synthetic route for the conversion of alkenes to conjugated nitroalkenes via nitro-mercuration and demercuration.74 Since then, many chemists have used this method for the preparation of cyclic nitroalkenes such as 1-nitrocyclohexene. However, the use of mercury salts is not recommended even for the small-scale preparation of nitroalkenes. This reaction is not as clean as expected, and formidable efforts are required to remove the mercury in the waste. 

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. 

Solvomercuration,3111 484 187 or the addition of mercury(II) salts, is a convenient route to organomercurials. On the other hand, replacement of mercury with hydrogen allows Markovnikov functionalization of alkenes.488 A method called mercuration-demercuration, for instance, has been developed for the Markovnikov hydration of alkenes under mild conditions489 [Eq. (6.82)490] ... 

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 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. 

Dienes can also be cyclized in a mercuration-demercuration process <7iocs7>. In extension of this work it has been found that 5,6-dihydroxy alkenes can also be converted to ds-2,5-disubstituted tetrahydrofurans by treatment with Cr(VI) (Equation (86)) it was established that the presence of both hydroxy groups is essential <74MI 207-02,82TL727, 88TL3171>. 

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 the oxymercuration step, water and mercuric acetate add to the double bond in the demercuration step, sodium borohydride reduces the acetoxymercury group and replaces it with hydrogen. The net addition of H — and —OH takes place with MaJ-kovnikov t oselectivity and generally takes place without the complication of rearrangements, as sometimes occurs with acid-catalyzed hydration of alkenes. The overall alkene hydration is not stereoselective because even though the oxymercuration step occurs with anti addition, the demercuration step is not stereoselective (radicals are thought to be involved), and hence a mixture of syn and anti products results. 

An improved method for the azidomercuration of alkenes with mercuric trifluoroacetate has been described.When applied to unsaturated carbohydrates it provides, after demercuration and reduction, a high-yielding synthesis of amino-sugars. 

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. 

There are several methods available for the electrophilic addition of hydrogen and nitrogen to alkenes, dienes and alkynes. While the direct electrophilic addition of amines to these substrates is not feasible, aminomercuration-demercuration affords a very useful indirect approach to such amines. The addition of amides to C—C multiple bonds can be effected directly through the Ritter reaction or by the less direct, but equally useful, amidomercuration-demercuration process using either nitriles or amides. Similarly, H—N3 addition to alkenes can be carried out directly or via mercuration to produce organic azides. 

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. 

The addition of mercuric acetate to an alkene in an alcohol solution, forming an alkoxymercu-rial intermediate. Demercuration gives an ether, (p. 342)... 

Coupling of ketones with electron-deficient alkenes via a methylene group (cf. 11, 315-316). This modified Giese reaction involves cyclopropanation of the silyl enol ether of a ketone, mercuration, and finally demercuration and coupling with an alkene via a radical chain reaction.7 Example ... 

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.)... 

We saw in Section 7.4 that aikenes 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 alkosymercuration reaction occurs when an alkene is treated with an alcohol in the presence of mercuric acetate. [Mercuric trifluoroacetate, (CF3C02)2Hg, 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. 

Oxymercuration-Demercuration Alkenes react with mercuric acetate in a mixture of water and tetrahydrofuran (THF) to produce (hydroxyalkyl)mercury compounds. These can be reduced to alcohols with sodium borohydride and water (Section 8.5). 

Aikoxymercuration reaction (Section 18.2) A method for synthesizing ethers by mercuric-ion catalyzed addition of an alcohol to an alkene followed by demercuration on treatment with NaBHi. 

The last example in Table 12-2 is an electrophilic addition of a mercuric salt to an alkene. The reaction is called mercuration, and the resulting compound is an alkyl-mercury derivative, from which the mercury can be removed in a subsequent step. One particularly useful reaction sequence is oxymercuration-demercuration, in which mercuric acetate acts as the reagent. In the first step (oxymercuration), treatment of an alkene with this species in the presence of water leads to the corresponding addition product. 

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