Solvomercuration

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]  

Hg(OAc)2 and Hg(OOCCFj)2 are the most frequently used reagents. Water and alcohols are the most common nucleophiles, and these processes are termed oxy-mercuration. Other additions are aminomercuration and peroxymercuration. 

Alkenes participate readily in oxymercuration with increasing alkyl-substitution resulting in decreasing reactivity.489,491,492 The oxymercuration of alkenes is usually an anti process.493 195 Exceptions are strained bicyclic olefins, such as norbomene495,496 [Eq. (6.83)],497 and frans-cyclooctene and frans-cyclononene.494 

The anti addition and the lack of rearrangements are compatible with a mechanism with the involvement of the cyclic mercurinium ion.493,495 Mercurinium ions are known to exist, for example, in superacidic media.498 

Only scattered information is available on oxymercuration of alkynes. Alkylphe-nylacetylenes were found to undergo stereoselective anti addition.500 Diphenylace-tylene, in contrast, gives only syn adducts.501 

The best characterized of these reactions involve the mercuric ion, Hg, as the cation. The usual nucleophile is the solvent. The term oxymercuration is used to refer to reactions in which water or an alcohol acts as the nucleophile. The adducts can be isolated as halide salts, but in synthetic applications the mercury is often replaced by hydrogen (oxymercuration reduction see below). 

The reactivity of mercury salts is a function of both the solvent and the counterion. Mercuric chloride, for example, is unreactive and mercuric acetate is the most commonly used reagent, but the trifluoroacetate, trifluoromethanesulfonate, nitrate, or perchlorate salts are preferable in some applications. 

Kitching, Organomet. Chem. Rev., 3, 61 (1968) R. C. Larock, Solvomercuration/Demercuration Reactions in Organic SyrUhesis, Springer-Verlag, New York, 1986. 

As expected for an electrophilic reaction, the p values for oxymercuration of styrene (-3.16) and a-methylstyrene (-3.12) derivatives are negative. The positive deviation of the methoxy substituent, when treated by the Yukawa-Tsuno equation, is indicative of a modestly enhanced resonance component. The additional methyl substituent in a-methylstyrene is slightly activating and indicates that its electron-donating effect outweighs any adverse steric effect. 

The addition of the nucleophile follows Markovnikov s rule and the regioselec-tivity of oxymercuration is ordinarily very high. Terminal alkenes are usually more than 99% regioselective and even disubstituted alkenes show significant regioselectivity, which is enhanced by steric effects. 

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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-demercuratton of alkenes with mercury(II) trifluoroacetate is a remarkably effective procedure for the preparation of esters and alcohols with Markovnikov s regiochemistry [52, 5J] (equation 24)... 

The solvomercuration reaction (Section 4.1.3) provides a convenient source of organomercury compounds such as 7-1 and 7-2. How can these be converted to functionalized lithium compounds such as 7-3 and 7-4 ... 

The solvomercuration of alkenes has been exhaustively studied and is now well understood. The mechanism of this reaction proceeds through two steps coordination of the mercuric ion to the alkene to form a fluxional cationic intermediate and subsequent nucleophilic anti-attack. Charge stabilization of the cationic intermediate constitutes one of the factors dictating the regioselectivity of the reaction (Scheme 11). 

Ring-closing reactions promoted by mercuric salts are valuable transformations which find an increasing use in the total synthesis of various natural products.130-140 Several examples of solvomercurations demonstrating the applicability of these transformations to the synthesis of natural product precursors are presented in Table 2. Piperidines (entry a), 141 pyrans (entries b-d), 142-144 and furans (entries e, f)14S>146 have been obtained in good yields and diastereoselectivity. These derivatives serve as starting materials for various natural products and can be demercu-rated under reducing conditions.147... 

Table 2 Selected examples of intramolecular solvomercuration of alkenes... 

When the alkynyl substrate possesses a nucleophilic functionality, intramolecular solvomercuration reactions can sometimes be observed. These reactions, which result in the formation of a heterocycle, have been used in the total synthesis of natural products. For example, reaction of 114 with Hg(OAc)2 affords the benzofuran derivative 115, which is an important intermediate for the synthesis of various neolignans (Equation (42)).154 155... 

Addition of electrophilic mercury(II) salts to carbon-carbon double bonds in nucleophilic solvents (i.e. oxymercuration, solvomercuration etc.) is a well documented methodology in organic synthesis146. In these reactions a mercuric salt, usually the chloride or... 

The solvomercuration reaction is thought to be a two-step process. In the first step (equation 147), electrophilic attachment of mercury ion to the alkene produces a positively charged intermediate. In the second step (equation 148), a nucleophile (generally a solvent molecule) reacts with the intermediate leading to the organomercury compound. 

Substituent effects on the solvomercuration reaction differ markedly from those on many other electrophilic additions and these have been explained by assuming that the formation of the intermediate is often rate limiting in electrophilic additions whereas the reaction of the ionic intermediate with nucleophiles is rate limiting in solvomercuration147. In other words, the solvomercuration involves a fast pre-equilibrium formation of an intermediate, followed by rate-limiting attack of the nucleophile on this species. 

Subsequent isolation of solvomercuration products has supplied information about the stereoselectivity of the mercury addition and at the same time has shown that these reactions can give 1,2- and/or 1,4-addition products. In particular, the identification by XH NMR spectroscopy of a 1,4-adduct from 1,3-pentadiene and mercury(II)nitrate in methanol has provided155 the first direct evidence that oxymercuration of conjugated dienes can proceed by 1,4-addition. Furthermore, the observed Z,E-isomerization of the diene has shown that the 1,4-oxymercuration is a reversible process. 

Organomercury compounds are also sources of alkyl radicals. Organomercurials can be prepared either by solvomercuration (Section 4.3) or from organometallic reagents (Section 7.3.3). 

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,),. ... 

Problem 14.5 Suggest a mechanism consistent with the following observations for the solvomercuration of RCH=CH, with R OH in the presence of HgfOAc) , leading to the formation of RCH(OR )CH,Hg(OAc) (i) no rearrangement, (ii) Markovnikov addition, (iii) anti addition, and (iv) reaction with nucleophilic solvents. 

Chiral solvomercuration was accomplished by carrying out the reaction of alkenes with Hg(OAc)2 in the presence of chiral quaternary ammonium salts synthesized from natural ephedrine.642 Chiral secondary alcohols may be isolated with ee values up to 96%. Chiral nitrogen-containing diselenides are transformed by perox-odisulfate to selenium electrophiles, which may add to alkenes to form oxyseleny-lation products. These are, however, not isolated but oxidized to induce oxidative p-hydride elimination to afford chiral allyl methyl ethers with ee values up to 75%.643... 

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