Thallium trifluoroacetate synthesis

Whilst direct electrophilic hydroxylation of the arylthallium species can be effected using peroxytriflu-oroacetic acid, further oxidation of the phenol to a quinone accompanies this process. This over-oxidation can be avoided by initial transmetallation to a lead species with concomitant reduction of the thallium trifluoroacetate (TTFA) by triphenylphosphine, followed by displacement of the lead by trifluo-roacetate to give the aryl trifluoroacetate. lliis hydroxylation method has yet to find use in the synthesis of molecules which are more complex than simple arenes. 

The synthesis of 7-methoxyindole was accomplished starting from 1-acetylindoline (34). Regioselec-tive introduction of iodine was achieved using thallium trifluoroacetate, then potassium iodide. Deacetylation and oxidation to the indole (35), followed by reaction with sodium methoxide in DMF, gave the... 

Yamamura and coworkers have used a thallium trifluoroacetate mediated oxidative cyclization in their synthesis of aerothionin and related products and also in the synthesis of bastadin-6, a 28-membered ring lactone. 

The synthesis of 7-methoxyindole was accomplished starting from 1-acetylindoline (34). Regioselec-tive intr uction of iodine was achieved using thallium trifluoroacetate, then potassium iodide. Deacetylation and oxidation to the indole (35), followed by reaction with sodium methoxide in DMF, gave the 7-methoxyindole (36) in 48% overall yield (Scheme 13). More recently, Somei et al have reported that treating the intermediate thallium species with copper(II) sulfate pentahydrate gives directly the l-acetyl-2,3-dihydro-7-hydroxyindole (37) in 42% yield (Scheme 14). It remains to be seen whether this is a general process. 

Although one-electron oxidation of arenes by thallium trifluoroacetate presumably does not proceed via formation of a discrete aiylthallium bond, some examples involving oxidative cyclization mediated by thallium trifluoroacetate will be considered here. Schwartz and Hudec employed thallium trifluoroacetate to effect an intramolecular cyclization of the amide (41) to give a key intermediate (42) in their projected synthesis of lycorine alkaloids (Scheme 16). Interestingly, when the bromine was replaced by a hyctogen the yield was poorer. 

Thallium trifluoroacetate has not enjoyed widespread use as a reagent for quinone synthesis, possibly because it is still a relatively new reagent but more probably because of its toxicity. One example of its use lies in the synthesis of metacyclophanes and related compounds as reported by Tashiro et al Thus the r-butylphenol (59) gave the bisquinone (61), while the phenol (60) afforded the monoquinone (62). An alternative and more practical synthesis of the bisquinone (61) for large scale work involved dealkylation to afford the bisphenol (63) which was then treated with sodium nitrite to give the bisoxime (64). Hydrolysis of the bisoxime did not give the quinone (61), but it could be obtained by zinc/acetic acid reduction of the bisoxime followed by oxidation with nitric acid (Scheme 13). 

Returning to phenol ether-phenol ether coupling, synthetic septicine (59) gave ( )-tylophorine (60) on treatment with thallium trifluoroacetate, and the same reagent converted synthetic julandine (61) to ( )-cryptopleurine (62 69%). In another synthesis of tylophorine the lactam (63) was transformed with va-... 

Aryl coupling to a benzylic site has also been observed the monophenol (67) yielded the aryltetralin (68 55%), with thallium trifluoroacetate-boron trifluoride. Probably oxidation to quinone methide precedes the ring closure. Separate oxidation and cyclization steps were employed in the synthesis of ( )-thaliphotphine acetate. ( )-Codamine (69) underwent Wessely oxidation with lead tetraacetate to the acetoxycyclohexadienone (70), which closed in acetic anhydride-acid to ( )-thaliphorphine acetate (71), albeit in modest overall yield (14%). ... 

Thallinm(ni) °, particnlarly as its triflnoroacetate salt , has been successfully used for the synthesis of phenols. This method can be carried out in a single step and is subject to isomer orientation control" . The aromatic compound to be hydroxylated is first thallated with thallium trifluoroacetate (TTFA)" and, by treatment with lead tetraacetate followed by triphenylphosphine and then dilute NaOH, it is converted to the corresponding phenol (equation 57). Table 1 shows some examples of these transformations . ... 

A new and efficient synthesis of ( )-cryptopleurine (Scheme 1) has been reported. " The piperidylacetophenone (30) was prepared from the benzoylacetic acid derivative (29) and A -piperideine, which was generated in situ from cadaverine and pea-seedling diamine oxidase. The enamine (31) undergoes cyclization and subsequent dehydration in the presence of a Lewis acid, and biaryl coupling is then effected with thallium trifluoroacetate. 

A significant improvement in the yield was also achieved in Takayama s concise synthesis of we.so-chimonanthine 121), via hypervalent iodine-mediated dimerization of a tryptamine precursor, giving we.so-chimonanthine in 30% yield over three steps (Scheme 12). This approach has also been applied by Takayama to the synthesis of chimonanthidine 108). A similar three-step procedure to we.so-chimonan-thine, albeit in lower overall yield, involving thallium trifluoroacetate-mediated oxidative coupling of the same tryptamine precursor has also been reported 122). 

Attention has also been called to thallium(III) salts for electrophilic metalation, and a number of procedures for synthesis of aromatic compounds via thallium intermediates have been reported." " A route to aryl iodides involves electrophilic substitution by thallium trifluoroacetate, followed by reaction with iodide ion ... 

Oxidation of 4H-pyran-4-thiones with thallium(III) trifluoroacetate was used in the one pot synthesis of l,6-dioxa-6n-thiapentalenes, a hypervalent heterocyclic system [57] (equation 27)... 

For example, photolysis of a suspension of an arylthallium ditrifluoro-acetate in benzene results in the formation of unsymmetrical biphenyls in high yield (80-90%) and in a high state of purity 152). The results are in full agreement with a free radical pathway which, as suggested above, is initiated by a photochemically induced homolysis of the aryl carbon-thallium bond. Capture of the resulting aryl radical by benzene would lead to the observed unsymmetrical biphenyl, while spontaneous disproportionation of the initially formed Tl(II) species to thallium(I) trifluoroacetate and trifluoroacetoxy radicals, followed by reaction of the latter with aryl radicals, accounts for the very small amounts of aryl trifluoroacetates formed as by-products. This route to unsymmetrical biphenyls thus complements the well-known Wolf and Kharasch procedure involving photolysis of aromatic iodides 171). Since the most versatile route to the latter compounds involves again the intermediacy of arylthallium ditrifluoroacetates (treatment with aqueous potassium iodide) 91), these latter compounds now occupy a central role in controlled biphenyl synthesis. 

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