Thallation of aromatics

Thallation of aromatic compounds with thallium tris(trifluoroacetate) proceeds more easily than mercuration. Transmetallation of organothallium compounds with Pd(II) is used for synthetic purposes. The reaction of alkenes with arylthallium compounds in the presence of Pd(Il) salt gives styrene derivatives (433). The reaction can be made catalytic by use of CuCl7[393,394], The aryla-tion of methyl vinyl ketone was carried out with the arylthallium compound 434[395]. The /9-alkoxythallium compound 435, obtained by oxythallation of styrene, is converted into acetophenone by the treatment with PdCh[396]. 

A simple, high-yield procedure for the conversion of ArTlXj into ArjTlX compounds has recently been described 90). This symmetrization reaction, the mechanism of which is not known, can be effected by treatment of the ArTlX2 compound either with triethyl phosphite or with hot aqueous acetone. As a wide variety of ArTlXj compounds can now be easily prepared by electrophilic thallation of aromatic substrates with thallium(III) trifluoroacetate (q. v.), symmetrization represents the method of choice for the preparation of the majority of ArjTlX compounds. Only about twenty mixed compounds, RR TIX, have been prepared so far, and the only general synthetic procedure available consists of a disproportionation reaction between an RTIX2 species and another organometallic reagent [e.g., Eqs. (5)-(7)]. 

Isomer Distributions in the Thallation of Aromatic Compounds at Room Temperature... 

Table 2. Yields from the Direct Thallation of Aromatic Compounds with Thallium(III) Tri-fluoroacetate...

Thallation of aromatic compounds with thallium tris(trifluoroacetate) proceeds more readily than mer-curation and in many instances more selectively. Ortho derivatives are obtained frequendy when functional groups with unshared electron pairs are present to direct the metallation.39... 

A very large number of other arylthallium bistrifluoroacetates have been obtained by the direct thallation of aromatic compounds 40, 168,169,170, 203) (see Section VIII, B). 

The colorless, photosensitive, hygroscopic solid, T1(02CCF3)3 is conveniently prepared by heating under reflux a suspension of TI2O3 in trifluoroacetic acid. A solution of this salt in the acid constitutes a powerful reagent for the direct thallation of aromatic compounds [Eq. (11)] (J6S). Such products are usually soluble in most organic solvents... 

Oxidation of aromatics by thallium trifluoroacetate in TFA at 20° also gives the cation radicals of alkylaromatics, and it is thought, because of this, that thallation of aromatics may involve cation radical formation first (Elson and Kochi, 1973). 

Thallium fill). - The electrophilic thallation of aromatic groups has led to new organothallium(III) species. 

Electrophilic mercuration and thallation of aromatic compounds, alkenes and alkynes are considered in Chapter 3. 

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. 

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 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. 

Thallationr-carbonylaiion of aromatics. ort/io-Thallation of benzoic acids, ben-zylic and (3-phenethyl alcohols, and benzamides followed by Pd(ID-catalyzed carbonyl-ation provides a route to aromatic carbonyl compounds such as phthalides, anhydrides, and imides. 

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. 

Although thallium(III) acetate fails to react with aromatic compounds under mild conditions, thallium (III) trifluoroacetate will effect rapid electrophilic thallation of a wide range of aromatic substances (40, 168, 169, 170, 203) according to the general reaction [Eq. (11)]. These reactions are very rapid and are usually completed in a few minutes at room temperature for activated aromatic nuclei, to give stable colorless solids that generally crystallize from solution. The orientation of thallation in such reactions may be influenced by temperature [Eq. (13)], or by the substituents on the aromatic nucleus. 

Aromatic iodides (3,287). The definitive paper on the synthesis of aromatic iodides by the reaction of arylthallium ditrifluoroacetates with potassium iodide has been published.1 Four procedures have been developed. 1) Thallation is carried out as usual and then an aqueous solution of potassium iodide is added directly. 2) The intermediate arylthallium ditrifluoroacetate is isolated and then treated with potassium iodide. 3) For acid-sensitive substrates solid TTFA in acetonitrile is used for thallation. 4) These methods are unsuccessful with highly reactive compounds such as naphthalene and diphenyl. In such cases molecular iodine is used as the electrophilic reagent and TTFA is used as oxidant for the hydrogen iodide formed in the reaction. 

Thallium(III) isobutyrate, a weak electrophile, limits the range of aromatic substrates that can be thallated. Even for activated substrates, 100-110 C is required. 

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. 

One important mechanism for homogeneous catalytic activation of aromatic C—H bonds is electrophilic attack by transition-metal complexes on the aromatic substrates. It is presumed t -aryl complexes are important intermediates in these reactions, but they are rarely isolated. Direct electrophilic metallation of aromatic substrates is closely related to reactions observed with nontransition metals ( 5.6., auration 5.7.2., mercuration and 5.3., thallation - ). References to metal-aryl complexes synthesized by electrophilic attack on arenes by transition metals are sununarized in Table 1. Reviews are available " . 

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