Aromatic thallation

TFA. Electrophilic aromatic thallation with TTFA therefore constitutes a simple and general procedure for the preparation of monoarylthallium(III) derivatives and has been the subject of detailed kinetic, mechanistic, and synthetic investigations. These aspects of the thallation reaction are discussed at length below. 

With the ArH ArTlX2 Arl reaction sequence available as a rapid and reliable probe for aromatic thallation, a detailed study was undertaken of the various factors affecting orientation in this electrophilic metallation process (153). The results, which are summarized below, demonstrate that aromatic thallation is subject to an almost unprecedented degree of orientation control coupled with the ease with which thallium can then be displaced by other substitutent groups (this aspect of the synthetic exploitation of aromatic thallation is discussed in detail below), the sequential processes of thallation followed by displacement represent a new and versatile method for aromatic substitution which both rivals and complements the classic Sandmeyer reaction. 

Aromatic thallation has been shown to be a reversible electrophilic substitution reaction with an energy of activation of approximately 27 kcal/mole and an extremely large steric requirement 153). The consequence of the latter feature of aromatic thallation is that there is a significant preference for para substitution in thallation of simple monosubstituted benzeno id compounds. It will be seen by examination of Table VI that the amount of para substitution increases as the size of the substituent increases (for... 

From the point of view of the synthetic organic chemist, the importance of aromatic thallation, and the remarkable degree of orientation control which can be exercised over this process, lies in the ease with which the resulting ArTlXj compounds can be converted into substituted aromatic derivatives in which the new substituent group has entered the ring at the position to which thallium was originally attached. Syntheses of phenols, nitroso compounds, biaryls, aromatic nitriles, thiophenols, and deuterated aromatic compounds have all been achieved these results are summarized briefly below. 

The aryl-thallium bond is thus apparently capable of displacement either by electrophilic or by suitable nucleophilic reagents. Coupled with its propensity for homolytic cleavage (spontaneous in the case of ArTlIj compounds, and otherwise photochemically induced), ArTlXj compounds should be capable of reacting with a wide variety of reagents under a wide variety of conditions. Since the position of initial aromatic thallation can be controlled to a remarkable degree, the above reactions may be only representative of a remarkably versatile route to aromatic substitution reactions in which organothallium compounds play a unique and indispensable role. 

The electrophilic thallation path involves [T1(TFA)2]+ as the active electrophile which forms a jt-complex with the substrate [16, 31]. Single electron transfer from electron-enriched polymethylarenes can be significant, leading to the formation of biaryls and side-chain thallated products [31]. The electron transfer path during electrophilic metalation is much more characteristic of T1(TFA)3 than Hg(TFA)2 [16], A review article [29] includes useful analysis of mechanistic features of aromatic thallation with T1(TFA)3 and some other Tl(III) reagents, including the even more electrophilic triflate. 

The reactions of aromatic substrates with thallium reagents is a fascinating subject which has been reviewed by McKillop and Taylor,two of the prime contributors to this field of chemistry. Two types of reaction are possible, both of which are important for the introduction of oxygen functionality. Tlie fu t is electrophilic aromatic thallation, whilst the second involves one-electron oxidation. 

Reaction of electron-rich aromatic compounds with TTFA leads to intermolecular oxidative coupling to form the corresponding biaryls without aromatic thallation. The reaction proceeds through one-electron transfer from aromatic compounds to Tl(III) to give an aromatic radical cation which leads to biaryls (Schemes 9.52 and 9.53 [52]). Intramolecular aryl coupling also occurs (Schemes 9.54 [53] and 9.55 [54]) and, further, when the carboxylic acid moiety is present, intramolecular as well as intermolecular lactonization occurs (Schemes 9.56 [55] and 9.57 [56]). 

Arylthallium(in) compounds (83) are generally prepared by electrophilic aromatic thallation with thallium tris(trifiuoroacetate) (84). 

Under conditions of kinetic control (low T and short times), the orientation of aromatic thallation relative to substituents on the ring may generally be predicted by normal meta- vs. ortho-para-directing character of the substituents . For ortho-para directors, para substitution predominates owing to the steric requirements of the Tl reagent. 

The acceptance of thallium(in) as a two-electron oxidant has received a setback from the report that cation radicals are readily formed in solution under thallation procedures by a one-electron oxidation. It is possible that such cation radicals are common intermediates in all aromatic thallations with thallium(iii) trifluoroacetate (see Scheme 25) other synthetic uses for the trifluoroacetate and its derivatives have been described. ... 

Thallium compounds, especially in the form of thallium(i) and thallium(iii) salts, are ahle to mediate a great numbers of reactions, including oxidative rearrangements of ketones and alkenes, cyclisation reactions, a-oxidation of ketones, aromatic thallations, oxidative couplings, oxidations of phenols and nitrogen compounds and disulfide bond formation, thus, constituting a useful tool in synthetic organic chemistry. However, their application as catalysts has been less explored and there are only a few successful examples reported in the literature. 

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