Electrophilic reactions mercury compounds

Organomercury reagents do not react with ketones or aldehydes but Lewis acids cause reaction with acyl chlorides.187 With alkenyl mercury compounds, the reaction probably proceeds by electrophilic attack on the double bond with the regiochemistry being directed by the stabilization of the (3-carbocation by the mercury.188... 

The chemistry of cyclopropanol [7] has long been studied in the context of electrophilic reactions, and these investigations have resulted in the preparation of some 3-mercurio ketones. As such mercury compounds are quite unreactive, they have failed to attract great interest in homoenolate chemistry. Only recent studies to exploit siloxycyclopropanes as precursors to homoenolates have led to the use of 3-mercurio ketones for the transition metal-catalyzed formation of new carbon-carbon bonds [8] (vide infra). 

Treatment of tetrazolium salts (154) with mercuric acetate gives the bistetrazolium mercury salts (155) which represent essentially a metal-carbene trapping of the tetrazolium ylide species. Replacement of the mercury atom of (155) is readily achieved with halogens to give the 5-halotetrazolium compounds (156) (93CB1149). These electrophilic reactions at the tetrazole C-5 arise from the lability of the 5-CH proton and they show the necessity of generating carbanionic character at C-5 before electrophilic attack can occur on this strongly ir-deficient azole. 

Mercury compounds are often used as electrophiles in displacements on organomercurials. There are five possible combinations of reactants in such mercury exchange reactions. A dialkylmercurial substrate may be attacked either by a mercury salt (Reaction 4.43) or by a monoalkylmercurial (Reaction 4.44) and likewise a monoalkylmercurial may react either with a mercury salt or with another monoalkylmercurial (Reactions 4.45 and 4.46). Finally, a dialkylmercurial may react with another dialkylmercurial (Reaction 4.47). (In Reactions 4.43-4.47 and in other reactions in this section, one of the reactants, and the fragments derived from that reactant in the products, are written in italics. This is done to make it easier to follow the course of the reaction.)... 

A systematic study of substitution reactions of oxazole itself has not been reported. Bromination of 2-methyl-4-phenyloxazole or 4-methyl-2-phenyloxazole with either bromine or NBS gave in each case the 5-bromo derivative, while 2-methyl-5-phenyloxazole was brominated at C(4). Mercuration of oxazoles with mercury(II) acetate in acetic acid likewise occurs at C(4) or C(5), depending on which position is unsubstituted 4,5-di-phenyloxazole yields the 2-acetoxymercurio derivative. These mercury compounds react with bromine or iodine to afford the corresponding halogenooxazoles in an electrophilic replacement reaction (81JHC885). Vilsmeier-Haack formylation of 5-methyl-2-phenyloxazole with the DMF-phosphoryl chloride complex yields the 4-aldehyde. 

Schemes 9-3 and 9-4 are sequences of two substitutions, first a metallo-de-hydrogenation, followed by a halogeno-de-metallation. Scheme 9-3 is analogous to the well known electrophilic aromatic sulfonation of anthraquinone in position 1. This isomer is obtained only if the reaction is run in the presence of catalytic amounts of mercury (ii) salts. Nowadays, however, larger effort is devoted to either replace mercury by other catalysts, or in the search for processes leading to (practically) complete recovery of the mercury. This case raises two questions with respect to the reaction sequence (9-3) first, whether it is possible to apply a one-pot process with catalytic amounts of a mercury compound (not necessarily HgO) to the synthesis of compounds 9.5, and second, whether mercury can be completely recycled in processes using either stoichiometric or catalytic amounts of the element.

The spectrum of mechanisms of the electrophilic substitution at a saturated carbon atom is very broad [1,72-74]. The bimolecular Se2 exchange reactions in the series of organo-mercury compounds have been studied in the most detailed manner. For these reactions as well as for the Se2 reactions of other organometallic compounds, the derivatives of Li, Mg, B, Sn, Ge, a four-center transition state of XXIV type is assumed ... 

DI- and Tri-anions.—Frequently, the formation of a multi-ion is necessary in order that a specific site in a molecule can be rendered active. This is especially so where that site is less easily lithiated than others within the molecule. Such a case presents itself with the dianions (36), where reaction occurs at the more reactive carbanionic centre to give access to various useful p-hydroxy-sub-stituted compounds from conventional electrophiles. " The requisite dianions can be formed from a-chloro-alcohols and a-chloro-ketones " or alternatively by lithiation of the corresponding mercurial compounds (S ). Since the mercurial compounds can in turn be obtained from an alkene by addition of Hg(OAc)a-H2X, in excellent yield, the method provides a very versatile synthesis of p-hydroxy-compounds from alkenes. The same authors have used the new trianions (38), again generated from a mercury compound by lithium-mercury... 

The synthetic utility of the mercuration reaction derives from subsequent transformations of the arylmercury compounds. As indicated in Section 7.3.3, these compounds are only weakly nucleophilic, but the carbon-mercury bond is reactive to various electrophiles. They are particularly useful for synthesis of nitroso compounds. The nitroso group can be introduced by reaction with nitrosyl chloride73 or nitrosonium tetrafluoroborate74 as the electrophile. Arylmercury compounds are also useful in certain palladium-catalyzed reactions, as discussed in Section 8.2. 

Electrophilic substitution at the anthraquinone ring system is difficult due to deactivation (electron withdrawal) by the carbonyl groups. Although the 1-position in anthraquinone is rather more susceptible to electrophilic attack than is the 2-position, as indicated by jt-electron localisation energies [4], direct sulphonation with oleum produces the 2-sulphonic acid (6.3). The severity of the reaction conditions ensures that the thermodynamically favoured 2-isomer, which is not subject to steric hindrance from an adjacent carbonyl group, is formed. However, the more synthetically useful 1-isomer (6.7) can be obtained by sulphonation of anthraquinone in the presence of a mercury(II) salt (Scheme 6.4). It appears that mercuration first takes place at the 1-position followed by displacement. Some disulphonation occurs, leading to the formation of the 2,6- and 2,7- or the 1,5- and 1,8-disulphonic acids, respectively. Separation of the various compounds can be achieved without too much difficulty. Sulphonation of anthraquinone derivatives is also of some importance. 

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. 

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. 

Much of the fundamental kinetic and mechanistic work on electrophilic substitution at saturated carbon has involved the study of reactions in which an organomercury substrate undergoes substitution by an electrophilic mercuric compound. Ingold and co-workers1 have concluded that these mercury-for-mercury exchanges occur only through the one-alkyl (1), the two-alkyl (2), and the three-alkyl (3) mercury exchange, viz. 

Compound 32 may be removed, after the Ugi reaction, under particularly mild conditions, thanks to sulfur activation by soft electrophiles, such as mercury salts. The yields obtained in zinc-mediated Ugi reactions are excellent and the diastereo-meric ratios are in line with those obtained with 27. Cleavage of the chiral auxiliary can be performed, after methylamine-promoted deacylation of the sugar hydroxy groups, by a diluted solution of CF3CO2H in the presence of Hg(OAc)2. Under these conditions the acyl group on nitrogen is retained. However, the enantiomer of 32 is not easily accessible. 

Acetyl hypofluorite also cleaves the carbon-mercury bond which provides an easy entry to many fluoroethers. Since the electrophilic fluorine attacks the electrons of the C—Hg bond, the reaction proceeds with a full retention of configuration. Several l-fluoro-2-methoxy derivatives were prepared from the corresponding olefins271, formally accomplishing the addition of the elements of MeOF across a double bond (equation 153)272. Such reactions were also used for the fluorination of very activated aromatic compounds (equation 154)273. 

In contrast to direct electrophilic substitution in which the astatine attacks one of the C—H bonds, astatination through demetalation can be used to label a substrate at a preferred site in a regiospecific manner not affecting other sensitive sites of the molecule. Since the C—M bond is more sensitive to electrophilic attack than C—H, higher yields can be obtained in short reaction times under milder experimental conditions56. Organometallic compounds of mercury, thallium and tin have been used so far for astatination via demetalation. 

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