Oxythallation reactions

Monoalkylthallium(III) compounds can be prepared easily and rapidly by treatment of olefins with thallium(III) salts, i.e., oxythallation (66). In marked contrast to the analogous oxymercuration reaction (66), however, where treatment of olefins with mercury(II) salts results in formation of stable organomercurials, the monoalkylthallium(III) derivatives obtained from oxythallation are in the vast majority of cases spontaneously unstable, and cannot be isolated under the reaction conditions employed. Oxythallation adducts have been isolated on a number of occasions (61, 71,104,128), but the predominant reaction pathway which has been observed in oxythallation reactions is initial formation of an alkylthallium(III) derivative and subsequent rapid decomposition of this intermediate to give products derived by oxidation of the organic substrate and simultaneous reduction of the thallium from thallium(III) to thallium(I). The ease and rapidity with which these reactions occur have stimulated interest not only in the preparation and properties of monoalkylthallium(III) derivatives, but in the mechanism and stereochemistry of oxythallation, and in the development of specific synthetic organic transformations based on oxidation of unsaturated systems by thallium(III) salts. 

The effect of structure of the alkyl group on the stability of monoalkyl-thallium(III) compounds can best be understood by reference to the different mechanisms by which these compounds undergo decomposition. A number of authors have attributed the instability of monoalkylthallium(III) compounds to facile C—T1 bond heterolysis and formation of carbonium ions [Eq. (25)] (52, 66, 79). This explanation is, however, somewhat suspect in cases where primary carbonium ions would be involved and either the two-step sequence shown in Eqs. (26), (27), or the fully synchronous 8 2 displacement shown in Eq. (28), is more compatible with the known facts. Examination of the oxythallation reactions that have been described reveals that Eq. (27) [or, for concerted reactions, Eq. (28)] can be elaborated, and that five major types of decomposition can be recognized for RTlXj compounds. These are outlined in Scheme 8, where Y, the nucleophile... 

Oxythallation reactions of olefins provide useful synthetic routes to products, eg, glycols, aldehydes, and ketones (31) ... 

Anchimeric assistance in oxymercurationand oxythallation reactions has been substantiated by the kinetic measurements of Halpern et al (see Table 18). When log k values for the alkenols in each reaction were plotted versus Taft s a constants (see Chapter 3) only l-penten-5-ol and l-hexen-6-ol fell off the lines (p in each case 3.2) defined by CH2=CHR, where R = alkyl or H. The positive deviation by l-penten-5-ol and 1-hexen-6-ol is good evidence for anchimeric assistance. Isolation of the furan and pyran derivatives expected from HO-5 and HO-6 involvement substantiate the claim of anchimeric assistance in oxymercuration. 

Interestingly, cyclic products are not found in the 0-5 and 0-6 assisted oxythallation reactions perhaps because of rearrangements during the dethallation step. The finding of the tetrahydrofuran products (235) and (237) after dethallation of the oxidation products of l-buten-4-ol (234)... 

Measurements of 2o /205 j ijj spin-spin couplings for the organothallium compounds formed in oxythallation reactions provides the first direct evidence for trans addition in the oxythallation of acyclic olefins. Products from the reactions of styrene, u-alkylphenols, propylene, and oct-l-ene were studied. The rate constants for the oxythallation of alkenes shows a reasonable correlation with the first ionization energy of the alkenes. Inductive effects were found to be most important in the oxythallation of RCH=CH2 and R R C=CHa alkenes. ... 

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]. 

Monoalkylthallium(III) compounds are unstable (73, 79), and very few examples of this class have been isolated. A number of alkylthallium diacetates have been obtained either from oxythallation of olefins with thallium-(III) acetate (see below) or from exchange reactions such as that shown in Eq. (11) (74, 75). Only four alkylthallium dihalides have been isolated so far, namely a neopentylthallium dihalide (60) [Eq. (12)] and the isomeric 2-, 3-, and 4-pyridiomethylthallium dichlorides (20) [Eq. (13)]. Monoaryl-and monovinylthallium(III) derivatives are considerably more stable than... 

Tl(III) < Pb(IV), and this conclusion has been confirmed recently with reference to the oxythallation of olefins 124) and the cleavage of cyclopropanes 127). It is also predictable that oxidations of unsaturated systems by Tl(III) will exhibit characteristics commonly associated with analogous oxidations by Hg(II) and Pb(IV). There is, however, one important difference between Pb(IV) and Tl(III) redox reactions, namely that in the latter case reduction of the metal ion is believed to proceed only by a direct two-electron transfer mechanism (70). Thallium(II) has been detected by y-irradiation 10), pulse radiolysis 17, 107), and flash photolysis 144a) studies, butis completely unstable with respect to Tl(III) and T1(I) the rate constant for the process 2T1(II) Tl(III) + T1(I), 2.3 x 10 liter mole sec , is in fact close to diffusion control of the reaction 17). 

Formation of mixtures of products in these reactions can be attributed largely to the properties of the acetate group. The reactions of a number of cycloalkenes with thallium(III) salts have been investigated in some detail and the results obtained have served both to elucidate the stereochemistry of oxythallation and to underline the important role assumed by the anion of the metal salt in these oxidations. The most unambiguous evidence as to the stereochemistry of oxythallation comes from studies by Winstein on the oxythallation of norbornene (VII) and norbornadiene (VIII) with thal-lium(III) acetate in chloroform, in which the adducts (IX) and (X) could be precipitated from the reaction mixture by addition of pentane 128) (Scheme 11). Both by chemical means and by analogy with the oxymercuration... 

Oxidation of the steroidal olefin (XXVII) with thallium(III) acetate gives mainly the allylic acetates (XXXI)-(XXXIII) (Scheme 15), again indicating that trans oxythallation is the preferred reaction course (19). Addition of the electrophile takes place from the less-hindered a-side of the molecule to give the thallinium ion (XXVIII), which by loss of a proton from C-4 would give the alkylthallium diacetate (XXIX). Decomposition of this intermediate by a Type 5 process is probably favorable, as it leads to the resonance-stabilized allylic carbonium ion (XXX), from which the observed products can be derived. Evidence in support of the decomposition process shown in Scheme 15 has been obtained from a study of the exchange reaction between frawr-crotylmercuric acetate and thallium(III) acetate in acetic acid (Scheme 16) (142). 

While the above examples demonstrate that product control to a significant extent is possible in oxythallation by careful choice of substrate or reaction conditions, the synthetic utility of oxythallation has been illustrated most convincingly by the results obtained with highly ionic thallium(III) salts, especially the nitrate (hereafter abbreviated TTN). Unlike the sulfate, perchlorate, or fluoroborate salts (165), TTN can easily be obtained as the stable, crystalline trihydrate which is soluble in alcohols, carboxylic acids, ethers such as dimethoxyethane (glyme), and dilute mineral acids. Oxidations by TTN can therefore be carried out under a wide variety of experimental conditions. 

These conclusions were supported by the results obtained in a study of the reactions of various types of acetylenes with TTN (94). Hydration of the C=C bond was found to occur to a very minor extent, if at all, with almost all of the compounds studied, and the nature of the products formed was dependent on the structure of the acetylene and the solvent employed. Oxidation of diarylacetylenes with two equivalents of TTN in either aqueous acidic glyme or methanol as solvent resulted in smooth high yield conversion into the corresponding benzils (Scheme 23). The mechanism of this oxidation in aqueous medium most probably involves oxythallation of the acetylene, ketonization of the initially formed adduct (XXXV) to give the monoalkylthallium(III) derivative (XXXVI), and conversion of this intermediate into a benzoin (XXXVII) by a Type 1 process. Oxidation of (XXXVII) to the benzil (XXXVIII) by the second equivalent of reagent would then proceed in exactly the same manner as described for the oxidation of chalcones, deoxybenzoins, and benzoins to benzils by TTN. The mechanism of oxidation in methanol solution is somewhat more complex and has not yet been fully elucidated. 

Thallium (III) Compounds. Thallium (ITT) derivatives have been used extensively as oxidants in oiganic synthesis. In particular, thallic acetate and trifluoroacetate are extremely effective as electrophiles in oxythallation and thallation reactions. For example, ketones can be prepared from terminal acetylenes by means of Tl(OOCCH3)3 in acetic acid (oxythallation) (30) ... 

As in all oxidations with T1(N03)3 oxythallation is the first step of the reactions. 9.3.2. Oxidative Cleavage... 

Another synthetic route to monoorganothallium compounds is the reaction of aryl or vinyl derivatives of mercury(II) or tin(IV) with TIX3 (X = halide, carboxy-late). Monoalkylthallium derivatives are intermediates m the oxidation of alkenes and alkynes by thallium(III) salts (oxythallation) (see Section 7). 

A similar reaction has been observed with the oxythallation adduct of styrene (272). In the presence of NaOAc the product is acetophenone dimethylacetal. When the reaction was run in CH3OD, again there was no deuterium incorporation in the product ... 

Further evidence for heterolytic decomposition is obtained from the effect of olefin structure on product distribution. Table II shows the ratio of carbonyl to glycol product for three olefins. Listed for comparison is the carbonyl/glycol ratio for the chlorohydrin, which corresponds to the structure of the oxythallation adduct from ethylene and propylene. The effect of structure on the ratio is qualitatively the same for the thallic ion oxidation and the hydrolysis of the corresponding chlorohydrin. Since the product distributions for both are inconsistent with neighboring hydroxyl participation (Reaction 33) the carbonyl/glycol ratio is a measure of the competition between hydride shift vs. water attack in... 

Kabbe (29) prepared an oxythallation adduct from o-allylphenol to give an ether-type adduct analogous to the mercury(II) adducts prepared some years ago by Adams (i ) (Reaction 59). 

No adduct is isolated in oxidizing cyclohexene in acetic acid, but oxidation in acetic acid gives mostly products which could result from decomposition of a rarw-oxythallation adduct with neighboring carbon or acetate participation (2) (Reactions 62, 63, and 64). 

When the reaction is applied to alkenes bearing a nucleophile in a suitable position, oxythallation occurs intramolecularly to furnish cyclic products via the corresponding oxythallated adducts (B) (Scheme 9.13). Several useful examples are chosen from many reported reactions (Schemes 9.14 [18], 9.15 [19], 9.16 [20] and 9.17 ]21]). 

Similarly to the reaction of arylthallium(III) compounds, the reaction of potassium iodide with (121), the product of oxythallation of alkenes, afforded the derived oxy-iodination product (123) in good yields through the alkylthallium diiodide intermediate (122). ... 

Other monovinylthallium(ni) compounds such as (132), the product of oxythallation of acetylenes, react analogously to the arylthallium compounds. Halogenodethallation and pseudohalogeno-dethallation reactions result from the interaction of the oxyalkenylthallium compound with either potassium iodide or with the appropriate copper derivatives. 6... 

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