Arenes mercuration

Another instructive scenario may be found when considering the metalation of arenes. There are two distinct mechanisms for the metalation of aromatic C-H bonds - electrophilic substitution and concerted oxidative addition (Box2). The classical arene mercuration, known for more than a century, serves to illustrate the electrophilic pathway whereas the metal hydride-catalyzed deuterium labeling of arenes document the concerted oxidative addition mechanism [8, 17]. These two processes differ both in kinetic behavior and regioselectivity and thus we may appreciate the need to differentiate these two types of process. However, the choice of C-H bond activation to designate only one, the oxidative addition pathway, creates a similar linguistic paradox. Indeed, it is hard to argue that the C-H bond in the cationic cr-complex is not activated. 

To date the mercurated arene radical cation is known for biphenylene [87], ace-naphthene, pyracene, hexahydropyrene, triptycene, p-terphenyl, tetramethylnaph-thopyran, anthracene, dibenzodioxin [89], and 4-tert-butylanisole [88]. In certain cases multiple mercuration is observed, for example in case of diphenylene [87] and dibenzodioxin [89]. Mercuration causes a decrease in -value and always occurs at the site where the local coefficient of the Huckel HOMO of the hydrocarbon is greatest, and there is a constant ratio of about 20.6 between the hyperfine couplings by the Hg [l, abundance 16.84 %) which has been introduced, and by the proton which has been displaced [89]. EPR spectroscopic evidence is reported for 8, 9, 10, 11, 12, 13, 14, 15 and 16 as new examples of recently recognized alternative mechanism of arene mercuration in which collapse of ArH +Hg(TFA)2 radical ion pair leads to arylmercury trifluoroacetate ArHg(TFA) + [90]. 

Main-group examples of C-H activation, such as arene mercuration, are long known, but tend to involve stoichiometric reagents, not catalysts, and many use metals that are now avoided on toxicity grounds (Hg, Tl, and Pb). Catalytic reactions involving transition metal organometallic activation and functionalization of C-H bonds (Section 12.4) are beginning to move into the applications phase and are likely to become much more common in synthesis." " Innate selectivity can sometimes permit functionalization of one out of the many... 

Reaction schemes. Arenes react with mercuric trifluoroacetate according to the equation29... 

The hemidecarboxylation of sodium phthaiate on reaction with mercuric acetate in boiling water [Eq. (82), X = H] (90) was the first reported thermal decarboxylation. The reaction has been observed for a number of arenes with two adjacent carboxylate groups (1-4,91) and has been named the Pesci reaction (91). Studies of 3-substituted sodium phthalates or of preformed mercuric 3-substituted phthalates have shown that the sterically hindered carboxyl group (the 2-carboxyl) is preferentially eliminated whether X is electron-donating or electron-withdrawing [Eq. (82), X = Me (91), Cl, N02 (91,93), Br (93), or C02H (94)]. A similar conclusion was drawn from the decomposition of mercuric 1,2-naph-thalenedicarboxylate and 3,4-phenanthrenedicarboxylate (91). 

The arene groups in (r/ -arcnc)tricarbonylchromium complexes are typically electron poor and display poor reactivity toward electrophiles. In the case of mercuration reactions, this lack of reactivity can be overcome by attachment of Lewis-basic substituents to the arene ring. For example, in the case of 75a-c, the presence of a pyridyl, oxazolyl, or methyl-A,A-dimcthylami no group promotes ortho-mercuration, leading to the formation of the bimetallic complexes 76a-c (Equation (28)). 07... 

Organic compounds Organic fluorine compounds arc made by reaction of the corresponding alkane chloro-compounds with silver fluoride, mercurous fluoride, antimony trifluoride, titanium tetrafluoridc. and the arene fluoro-compounds by the diazo-reaction using hydrogen fluoride, and otherwise. The effect of the continued replacemenl of hydrogen atoms by fluorine atoms is an initial increase in reactivity, followed by a reversal of this effect, so lhal the highly substituted compounds arc relatively inert, See also Fluorocarbon. 

Because metals are electropositive elements they can be considered potential electrophiles. Their reactions with arenes have been investigated most thoroughly for mercury. Benzene can be substituted with HgX derived from a mercuric salt, HgX2, in the presence of an acid catalyst. The salt most com-... 

Aromatic ketones arylations, 10, 140 asymmetric hydrogenation, 10, 50 G—H bond alkylation, 10, 214 dialkylzinc additions, 9, 114-115 Aromatic ligands mercuration, 2, 430 in mercury 7t-complexes, 2, 449 /13-77-Aromatic nitriles, preparation, 6, 265 Aromatic nucleophilic substitution reactions, arene chromium tricarbonyls, 5, 234... 

Dichloroiodo)arenes may also be converted to (diacetoxyiodo)arenes upon treatment with mercuric acetate. This approach and also perborate oxidation of iodides were used for the preparation of some chiral l,l -binaphthyl derivatives [28]. 

Kinetic experiments have demonstrated that the mercuration of benzene with mercury acetate or nitrate is second order, first order in each of the mercury salt and the arene [7]. Electron-donating substituents on the ring increase mercuration rates, whereas electron-withdrawing groups slow down the reaction [7-11]. For example, mercuration of nitrobenzene requires 150 °C to occur and reaction of benzene with Hg(OAc)2 in AcOH takes hours at 90-120 °C whereas N,N-dimethy-laniline readily reacts with Hg(OAc)2 in aqueous EtOH at room temperature within a few minutes [7]. 

Lead(IV) trifluoroacetate in TFAH is a very reactive electrophile that is capable of plumbylating less electron-rich arenes. Nonetheless, the use of trifluoroacetate anions in the plumbylation reactions should be avoided, because aryllead(IV) tri-fluoroacetates are unstable compounds that readily decompose to the corresponding aryl trifluoroacetates and biaryls [34—37, 40, 41]. It has been reported [41] that 4-FC6H4ArPb(TFA)3 is reasonably stable and can be isolated from the reaction of Pb(TFA)4/TFAH with fluorobenzene. A mechanistic study [41] indicated an electrophilic substitution path for the plumbylation reaction, which seemed to be substantially more para-selective than mercuration and thallation. For example, the plumbylation of toluene with Pb(OAc)4 in dichloroacetic acid has been reported [41] to occur with >90 % para-selectivity. 

The most practical method for the preparation of (difluoroiodo)arenes is from (dichloroiodo)arenes on reaction with mercuric oxide and hydrofluoric acid. 

The (dichloroiodo)arene (40 mmol) and finely ground yellow mercuric oxide (10.8 g, 50 mmol) were shaken in a polyethylene bottle with dichloromethane (100 ml). Hydrofluoric acid (48%, 10 ml) was added and the bottle shaken vigorously for about 1 min. The colour of the solution turned from bright yellow to nearly colourless. Then the solvent phase was carefully decanted. The residue was shaken with dichloromethane (50 ml) which was combined with the original solution. The reagent formed was used in this solution for fluorination. In order to find its titre, a portion (1 ml) was analysed by titration of the iodine liberated by reaction with aqueous potassium iodide. The yield was calculated to be in the range 60-90%. 

Similarly, unactivated arenes readily react with thallium(III) trifluoroacetate in TFA to give the corresponding arylthallium trifluoroacetates, ArTl(02CCF3)2, which are stable and do not readily decompose to aryl trifluoroacetates and T1(I) 282-286 The rate of aromatic mercuration is increased by a factor of 7 X 10s in TFA relative to acetic acid as solvent.292... 

Perchloric acid increased the electrophilicity of Pd(II). A strong parallel between palladation and mercuration of aromatic hydrocarbons was drawn.568 (The effect of strong acids in increasing the electrophilicity of metal acetates has been discussed earlier.) Arylmercury complexes are relatively stable and do not afford biaryl readily. Analogous arylthallium(III) complexes only afford biaryls on photolysis in the presence of arenes via the following sequence ... 

The carboxylates of indium and thallium are obtained by dissolving the oxides in acid. Acetate and trifluoroacetate salts are used extensively as reagents in organic synthesis. Certain other thallium compounds have been used also. The trifluoroacetate, T1(02CCF3)3, will directly thallate aromatic compounds to give arylthal-lium species, for example, C6H5T1(02CCF3)2 (cf. aromatic mercuration, Section 15-15) and oxidize arenes to biaryls. 

Figure 6 Direct relationship of the relative reactivities (Jt i) of arenes in mercuration and thallation...

The linear free enogy relationship obsoved for arene donors relates the activation barrier AG for aromatic substitution directly to the CT transiticxi oiergy Aver of the EDA complex. Since Aver pertains to the energetics of the photoionizadons in equations (27) and (28), the correlation suggests that these arene contact ion pairs ate reasonable approximatims to the transition states for both mercuration and thallation, e.g. Scheme 6. 

Indeed the diversion to side products during thallation coincides with the direct obsovation of the arene radical cation as a transient intermediate both by UV-visible and ESR spectroscopy. A similar dichotomy between the products of mercuration and thallation exists with durene, albeit to a lesser degree. Finally no discrepancy is observed with mesitylene, nuclear substitution occuiring exclusively in both mercuration and thallation. Such a divergence between mercuration and thallation can be reconciled by the formulation in Scheme 6 if they difier by the extent to which di sive separation (ki) occurs in equation (31). All factors being the same, diffusive separation of the radical pair from thallium(III) should... 

The study of mercuration and thallation provides a shaip focus on the experimental delineation of stepwise and concerted mechanisms for arene activation. Thus the unequivoc demonstration of arene radical cations as key intermediates in thallation, particularly of durene and pentamethylbenzene, is consistent with a stepwise (electron-transfer) mechanism for arene activation (compare Scheme 6 and equation 39). 

By the same token, the singular absence of any experimental evidence for such intermediates during mercuration is directly accommodated by a concerted (electrophilic) mechanism for arene activation, i.e. equation (40). 

The direct mercuration of arenes is widely used for the synthesis of arylmercurials. The reaction is particularly efficient for activated arenes (such as phenols, anilines, and aryl ethers), while deactivated arenes require the use of stronger electrophiles and higher reaction temperatures. A recent example of the latter is the mercuration of terephthaldehyde reported by Vicente (equation 6) ... 

---