Electrophilic aromatic mercuration

This st example of C-H activation with a metal compound is the electrophilic aromatic mercuration of benzene using Hg(OAc)2 which was reported by Dimroth in 1898. This reaction is the analog of Friedel-Crafts reactions that use organic... 

Nitration in sulphuric acid is a reaction for which the nature and concentrations of the electrophile, the nitronium ion, are well established. In these solutions compounds reacting one or two orders of magnitude faster than benzene do so at the rate of encounter of the aromatic molecules and the nitronium ion ( 2.5). If there were a connection between selectivity and reactivity in electrophilic aromatic substitutions, then electrophiles such as those operating in mercuration and Friedel-Crafts alkylation should be subject to control by encounter at a lower threshold of substrate reactivity than in nitration this does not appear to occur. 

Whereas most reactions in the isoxazole series are undoubtedly those of electrophilic substitution, mercuration of isoxazoles, as well as some cases of mercuration of aromatic compounds, could be considered as homolytic reactions. However, the ready mercuration of... 

Mercuration of aromatic compounds can be accomplished with mercuric salts, most often Hg(OAc)2 ° to give ArHgOAc. This is ordinary electrophilic aromatic substitution and takes place by the arenium ion mechanism (p. 675). ° Aromatic compounds can also be converted to arylthallium bis(trifluoroacetates), ArTl(OOCCF3)2, by treatment with thallium(III) trifluoroacetate in trifluoroace-tic acid. ° These arylthallium compounds can be converted to phenols, aryl iodides or fluorides (12-28), aryl cyanides (12-31), aryl nitro compounds, or aryl esters (12-30). The mechanism of thallation appears to be complex, with electrophilic and electron-transfer mechanisms both taking place. 

Aromatic compounds react with mercuric salts to give arylmercury compounds.69 Mercuric acetate or mercuric trifluoroacetate are the usual reagents.70 The reaction shows substituent effects that are characteristic of electrophilic aromatic substitution.71 Mercuration is one of the few electrophilic aromatic substitutions in which proton loss from the a complex is rate determining. Mercuration of benzene shows an isotope effect kB/kD = 6,72 which indicates that the [Pg.1026]

A specific case of the carbonium ion mechanism [Eq. (5)] with reasonable plausibility is decarboxylation of metal arenoates by classic electrophilic aromatic substitution [Eq. (12)]. This mechanism would be favored by electron-donating substituents and has been invoked to explain the relative ease of decarboxylation of p-methoxybenzoic acid in molten mercuric trifluoroacetate (77) as well as the very facile decarboxylation on reaction of polymethoxybenzoic acids with mercuric acetate (18) (see below). 

Successful thermal decarboxylation of metal arenoates other than poly-halogenoarenoates are restricted to mercury compounds and fall into three categories, namely (i) those where electron-withdrawing substituents other than halogens are present in the organic groups, (ii) those where substituents and/or conditions are used which favor a different mechanism, e.g., classic electrophilic aromatic substitution, or (iii) those where the conditions are sufficiently forcing for both mercuration and decarboxylation to occur. 

Successful decarboxylations where the substituents favor classic electrophilic aromatic substitution are known. Reaction of 2-hydroxy-l-naphthalenecarboxylic acid with mercuric acetate in cold acetic acid has been reported to give 2-hydroxynaphthalen-l-ylmercuric acetate [Eq. (71)] (84). Although the result probably requires reinvestigation,... 

The selective electrophilic aromatic substitution carried out by displacement of a metallic substituent (Hg, Sn) ( F-fluorodemetallation) using [ F]p2 or [ F]AcOF remains a method of choice to introduce a fluorine atom on a specific position. In the early preparations of [6- F]fluoro-L-DOPA, the reaction of a 6-substituted mercuric derivative with [ F]acetyl hypofluorite yielded the expected compound in 11 % yield [73,74]. Reaction of a mercuric precursor, free or on a modified polystyrene support P-CH2-COOHg(DOPA precursor) allows the preparation of [ F]fluoro-L-DOPA in an overall yield up to 23 %. The polymer supports are easily prepared, require no special treatment for storage and are convenient to use in automated production [75]. 

Aromatic compounds react with mercuric salts to give arylmercury compounds.63 The reaction shows substituent effects that are characteristic of electrophilic aromatic... 

The partial rate factors af and /3f for the a- and /3-positions of thiophene have been calculated for a wide range of electrophilic reactions these have been tabulated (71 AHC(13)235, 72IJS(C)(7)6l). Some side-chain reactions in which resonance-stabilized car-benium ions are formed in the transition states have also been included in this study. A correspondence between solvolytic reactivity and reactivity in electrophilic aromatic substitution is expected because of the similar electron-deficiency developed in the aromatic system in the two types of reactions. The plot of log a or log /3f against the p-values of the respective reaction determined for benzene derivatives, under the same reaction conditions, has shown a linear relationship. Only two major deviations are observed mercuration and protodemercuration. This is understandable since the mechanism of these two reactions might differ in the thiophene series from the benzene case. 

Discovered over a century ago, electrophilic mercuration is probably the oldest known C-H bond-activation reaction with a metal compound. The earliest examples of aromatic mercuration were reported by Volhard (mercuration of thiophene) [1], Pesci (mercuration of aromatic amines) [2], and Dimroth [3], who was the first to mercurate benzene and toluene, generalize the reaction, and assign the correct structures to the products originally observed by Pesci. Since the work of Dimroth electrophilic aromatic metalation reactions with compounds of other metals, for example Tl(III), Pb(IV), Sn(IV), Pt(IV), Au(III), Rh(III), and Pd(II), have been discovered [4], In this chapter, we will focus on intermolecular SEAr reactions involving main-group metal electrophiles and resulting in the formation of isolable metal aryls which find numerous important applications in synthesis [5], Well-known electrophilic cyclometalation reactions, for example cyclopalla-dation can be found in other chapters of this book and will not be reviewed here. 

Numerous studies have revealed an electrophilic mechanism of aromatic mercuration. For example, the reactivity of a mercurating agent HgX2 strongly... 

R. Taylor Kinetics of electrophilic aromatic substitution. Sections 7 (Mercuration) and 9 (Protodemetallation) are noteworthy for their comprehensive coverage. 

Iv) Aromatic Mercuration . Aromatic compounds are metallated by electrophilic Hg salts ... 

Perchloric acid strongly accelerates aromatic mercuration in acetic acid solution it converts mercuric acetate into a positively charged electrophile.24b,c,d... 

In reactions like aromatic mercuration, palladium(II) compounds will metaUate aromatic rings via an electrophilic substitution, hence electron-rich systems are the most reactive. ortfto-Palladation assisted by electron-releasing chelating groups has been used frequently."°... 

Complex 13 undergoes electrophilic substitution with aromatic substrates. Thus, treatment with benzene in dichloromethane at ambient temperature results in the formation of the diphenyl complex 15 (Scheme V. Reaction of 13 with pyridine (5-6 equivs) in dichloromethane affords a new complex that is the result of pyridine a-CH activation. The NMR data clearly show two chemically equivalent coordinated pyridines and pyridine that has lost one of the a-hydrogens. Structure 16 is proposed from the preliminary data. The formation of 15 and 16 was quantitative by NMR monitoring, but these compounds are reactive and have not been isolated as pure solids. While main group Lewis acids are well known to undergo aromatic substitutions (e.g., mercurations, thallations, etc.) (33), relatively little is known about the ability of transition metal complexes to undergo electrophilic aromatic substitution (34). 

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