Electrophilic mercury

Electrophilic mercuration has been well established in aromatic substitu-tion . The corresponding mode of addition to olefins has been a source of continual controversy. While there is no doubt that a homolytic mechanism is involved in, for instance, the addition of mercuric acetate to cyclohexene in methanol, a reaction which is catalysed by peracetic acid, there seems no reason to discount heterolytic processes under more suitable conditions. The earlier literature has been critically reviewed and assessed on this point. The first reaction product has been thought to involve a mercurinium ion (IV).  

Such a structure is analogous to those suggested for halogen addition, acid-catalysed hydration, and sulphenyl halide addition, but has. suffered severe criticism. To follow the analogy, such an intermediate would be expected to 

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O The alkyne uses a pair of electrons to attack the electrophilic mercury(II) ion, yielding a mercury-containing vinylic carbocation intermediate. 

Hawthorne and co-workers have also produced a series of macrocyclic Lewis acid hosts called mercuracarborands (156, 157, and 158) (Fig. 84) with structures incorporating electron-withdrawing icosahedral carboranes and electrophilic mercury centers. They were synthesized by a kinetic halide ion template effect that afforded tetrameric cycles or cyclic trimers in the presence or absence of halide ion templates, respectively.163 These complexes, which can bind a variety of electron-rich guests, are ideal for catalytic and ion-sensing applications, as well as for the assembly of supramolecular architectures. 

Figure 84 Macrocyclic mercuracarborands (156, 157, and 158) with structures incorporating electron-withdrawing icosahedral carboranes and electrophilic mercury centers. (Adapted from ref. 163.)... 

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... 

Oxymercuration in dichloromethane at room temperature afforded the adducts 190 and 191 from 188 (equation 162), and 192 and 193 from 189 (equation 163), the electrophilic mercury attack preferentially occurring at the C(3) carbon atom. A similar selectivity was previously observed also in OM-DM of 188165. 

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. 

One major advantage of the alkoxymercuration-demercuration approach to ethers over the acid-catalyzed process is the fact that carbon skeleton rearrangements are seldom observed. Only unsaturated cyclopropanes,42S>426 or aryl-substituted alkenes427 428 in the presence of highly electrophilic mercury salts afford rearranged products. 

Yang, X. G., Knobler, C. B., Zheng, Z. P., Hawthorne, M. F., Host-guest chemistry of a new class of macrocyclic multidentate lewis-acids comprised of carborane-supported electrophilic mercury centers. J. Am. Chem. Soc. 1994,116, 7142-7159. 

Figure 11.5 shows a mechanism that has been postulated for this reaction. First, an electrophilic mercury species adds to the double bond to form a cyclic mercurinium ion. Note how similar this mechanism is, including its stereochemistry and regiochemistry, to that shown in Figure 11.4 for the formation of a halohydrin. The initial product results from anti addition of Fig and OH to the double bond. In the second step, sodium borohydride replaces the mercury with a hydrogen with random stereochemistry. (The mechanism for this step is complex and not important to us at this time.) The overall result is the addition of H and OH with Markovnikov orientation. 

There are some examples of nucleophilic displacement of a suitably activated bromine by fluoride, but there have been instances where such reactions are unsuccessful <93AHC(57)291>. Electrophilic methods do not include direct fluorination, but metallic derivatives provide carbanions which react with fluorine sources. Thus, 2- and 4-fluoroimidazoles have been made from the lithioimidazoles, for example, perchloryl fluoride converts 2-lithio-l-methylimidazole into the 2-fluoro derivative in more than 50% yield. Access to 4- and 5-fluoroimidazoles is even more convenient from the trimethylstannyl derivatives using fluorine or caesium fluoroxysulfate as the electrophile . Mercury groups react in much the same way, but they are more difficult to prepare and purify <86BSF930>. 

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. 

A more recent application of a similar cyclization is during a synthesis of (+)-preussin 230 in which a key step is mercury(II)-induced cyclization of the ynone 228 to give the keto-dihydropyrrole 229 <94JOC4721>. There are a number of notable features of this reaction. Firstly, despite conjugation to the keto group, the alkyne remains sufficiently nucleophilic to interact with the electrophilic mercury, the intermediate ketone is stable to racemization and the Af-Boc group does not interfere, presumably because the 5-endo-dig mode is favoured. 

Mercuration with mercuric acetate reveals a regioselectivity pattern similar to that observed for the hydrogen halides. The electrophilic mercury is found on the terminal carbon for allene, but on the 2-carbon for 1,1-dimethylallene. Products... 

A more recent synthesis of 3-methylenecephams from cephalosporins utilizes mercury salts in a metal-assisted reaction with 3-methyl-3-hal-ocepham ester sulfoxides. Although ordinarily dehydrohalogenations of 3-halo-3-methylcephams lead to the thermodynamically more stable 3-methyl-2-cephems and -3-cephems, chemists at Dista Products Limited (England) discovered that electrophilic mercury salts specifically led to 3-methylenecephams (Corfield and Taylor, 1978). When p-nitrobenzyl 7-phenoxyacetamido-3-methyl-3-bromo(or 3-iodo)cepham-4-carboxylate 1-oxide (47) was treated with mercury(I or II) perchlorate in dimethox-yethane for 18 hr at room temperature, p-nitrobenzyl 7-phenoxyacetam-ido-3-methylenecepham-4-carboxylate 1-oxide (48) was obtained in 75% yield. No other metal salt (in a variety of solvents) effected this transformation. Their view of the mechanism of this reaction is detailed later in this chapter. 

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