Oxymercuration mechanism

In the first step of the oxymercuration mechanism, the electrophilic mercury of mercuric acetate adds to the double bond. (Two of mercury s 5d electrons are shown.) Because carbocation rearrangements do not occur, we can conclude that the product of the addition reaction is a cyclic mercurinium ion rather than a carbocation. The reaction is analogous to the addition of Br2 to an alkene to form a cyclic bromonium ion. 

Figure 7.3 Mechanism of the oxymercuration of an alkene to yield an alcohol. The reaction involves a mercurinium ion intermediate and proceeds by a mechanism similar to that of halohydrin formation. The product of the reaction is the more highly substituted alcohol, corresponding to Markovnikov regiochemistry.

I Review the mechanism of oxymercuration shown in Figure 7.4 (p. 225), and then i write the mechanism of the alkoxymercuration reaction of 1-methylcvclopentene with ethanol. Use curved arrows to show the electron flow in each step. 

Although alkyl groups in general increase the rates of electrophilic addition, we have already mentioned (p. 974) that there is a different pattern depending on whether the intermediate is a bridged ion or an open carbocation. For brominations and other electrophilic additions in which the first step of the mechanism is rate determining, the rates for substituted alkenes correlate well with the ionization potentials of the alkenes, which means that steric effects are not important. Where the second step is rate determining [e.g., oxymercuration (15-3), hydroboration (15-17)], steric effects are important. ... 

Monoalkylthallium(III) compounds can be prepared easily and rapidly by treatment of olefins with thallium(III) salts, i.e., oxythallation (66). In marked contrast to the analogous oxymercuration reaction (66), however, where treatment of olefins with mercury(II) salts results in formation of stable organomercurials, the monoalkylthallium(III) derivatives obtained from oxythallation are in the vast majority of cases spontaneously unstable, and cannot be isolated under the reaction conditions employed. Oxythallation adducts have been isolated on a number of occasions (61, 71,104,128), but the predominant reaction pathway which has been observed in oxythallation reactions is initial formation of an alkylthallium(III) derivative and subsequent rapid decomposition of this intermediate to give products derived by oxidation of the organic substrate and simultaneous reduction of the thallium from thallium(III) to thallium(I). The ease and rapidity with which these reactions occur have stimulated interest not only in the preparation and properties of monoalkylthallium(III) derivatives, but in the mechanism and stereochemistry of oxythallation, and in the development of specific synthetic organic transformations based on oxidation of unsaturated systems by thallium(III) salts. 

From the evidence currently available it appears that the mechanism of oxythallation is similar to that of oxymercuration. That is, initial rapid formation of a 7r-complex—a thallinium ion—followed by rearrangement of this species to give a o-bonded organothallium derivative (54). Decomposition of this latter intermediate by one or more of the processes shown in Scheme 8 then leads to products. The results obtained from a number of kinetic studies are in broad general agreement with this interpretation (52,79). 

The relative reactivity profile of the simple alkenes toward Wacker oxidation is quite shallow and in the order ethene > propene > 1-butene > Zi-2-butene > Z-2-butene.102 This order indicates that steric factors outweigh electronic effects and is consistent with substantial nucleophilic character in the rate-determining step. (Compare with oxymercuration see Part A, Section 5.8.) The addition step is believed to occur by an internal ligand transfer through a four-center mechanism, leading to syn addition. 

The R—0—B bonds are hydrolysed in the alkaline aqueous solution, generating the alcohol. The oxidation mechanism involves a series of B-to-0 migrations of the alkyl groups. The stereochemical outcome is replacement of the C—B bond by a C—O bond with retention of configuration. In combination with the stereospecific syn hydroboration, this allows the structure and stereochemistry of the alcohols to be predicted with confidence. The preference for hydroboration at the least substituted carbon of a double bond results in the alcohol being formed with regiochemistry which is complementary to that observed in the case of direct hydration or oxymercuration, that is, anti-Markownikoff. 138... 

Oxymercuration of 4-/ -butyIcycIohcxcnc, followed by NaBH4 reduction, gives c/.v-4-/-butylcyclohexanol and Ira / , v - 3 - / - b u ty I eye I o h c x a n o I in approximately equal amounts. l-Methyl-4-t-butylcyclohexene irnder similar conditions gives only c/.v-4-/-butyl-1 -methylcyclohexanol. Formulate a mechanism for the oxymercuration-reduction process that is consistent with this stereochemical result. 

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. 

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. 

It is clear that the mechanism in Scheme 25 parallels (at least from the qualitative point of view) the mechanism of the addition of bromine to olefins shown in Scheme 11. Kinetic investigations indicate that the oxymercuration reaction involves a series of fast equilibria until the mercuronium ion (53) is formed. The subsequent nucleophilic attack of the solvent is probably the rate-limiting step, as indicated by steric requirements in bulky alkenes111. In the bromine addition, the formation of the bromonium ion is the rate-limiting step (or the rate-limiting equilibrium). However, the olefin reactivities in both reactions (bromination and oxymercuration) are identical when steric effects in the TS of the two addition reactions are taken into account110. 

The PM3 and ab initio calculations have been employed to compare mercuronium and bromonium ions 55 and 52111. Experimental comparison of the mechanism of the oxymercuration and bromination has also been made (see the section on bromination)142. 

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... 

This halonium ion mechanism can be used to explain and predict a wide variety of reactions in both nucleophilic and non-nucleophilic solvents. The halonium ion mechanism is similar to the mercurinium ion mechanism for oxymercuration of an alkene, and both give Markovnikov orientation (Section 8-5). 

Problem 18.4 Review the mechanism of oxymercuration shown in Figure 7.4 (p. 225), and then... 

The use of cyclopropyl substituent effects was applied as a diagnostic tool for the elucidation of the mechanism of two much more ambiguous reactions, namely meth-oxymercuration and bromination . In the former reaction c-PrCH=CH2 is 410 times as reactive as 1-hexene, and (c-Pr)2 C=CH2 and c-PrCMe=CH2 are even more reactive. In contrast the isomeric c-PrCH=CHMe were even less reactive than 1-hexene. These rate... 

Cis additions occur exclusively to trans-cyclooctene and trans-cyclononane . For these two alkenes, trans addition is hindered. The tendency of an alkene to oxymercurate via a trans mechanism can be related directly to its ability to form the normal anti transition state . If for either steric or twist-strain reasons this transition state is made energetically unfavorable, cis-addition prevails. 

The mechanism of the mercurydD-catalyzed alkyne hydration reactioi is analogous to the oxymercuration reaction of alkenes (Section 7.4). Elec trophilic addition of mercury(II) ion to the alkyne gives a vinylic cation which reacts with water and loses a proton to yield a mercury-containii enol intermediate. In contrast to alkene oxymercuration, no treatment widi NaBH4 is necessary to remove the mercury the acidic reaction conditions alone are sufficient to effect replacement of mercury by hydrogen (Figure 8.3). 

For example, a mixture of 10.0 mmoles of mercuric acetate, 10 ml. of water, and 10 ml. of tetrahydrofurane is stirred mechanically in a small flask, 10 mmoles of 1-hexene is added and the mixture is stirred for 10 min. at 25° to complete the oxymercuration stage. Then 10 ml. of 3 M sodium hydroxide is added, followed by 10 ml. of a solution of 0.5 M sodium borohydride in 3 M sodium hydroxide. Reduction of the oxymercurial is almost instantaneous. The mercury is allowed to settle, and sodium chloride is added to saturate the water layer. The upper layer of THF is separated and contains 2-hcxanol in essentially quantitative yield. 

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