[4832-52-4]  · C19H16S3  · Tris(phenylthio)methane  · (MW 340.56)

(precursor to tris(phenylthio)methyllithium, used for nucleophilic carboxylation;1 electrophilic formylating agent for aromatic compounds2 and diazo esters3)

Physical Data: mp 40-41 °C.

Solubility: freely sol most organic solvents; usually used in THF, methylene chloride, or ether.

Form Supplied in: off-white to pale yellow solid, typically 97-99% pure; commercially available.

Analysis of Reagent Purity: the NMR spectrum will establish the absence of ethyl formate, the usual precursor to the reagent. Residual thiophenol can be removed by washing an ethereal solution of the reagent with 1 N NaOH followed by standing under high vacuum.

Handling, Storage, and Precautions: is stable indefinitely if stored at ambient temperatures in tightly sealed containers to exclude moisture, which promotes hydrolysis to thiophenol and formic acid. The presence of residual thiophenol mandates that the reagent be handled in a fume hood to avoid inhalation of dust and that skin contact be avoided.

Nucleophilic Carboxylation.

The reagent, in THF or ether solution, is quantitatively converted to its lithiated derivative with 1 equiv of n-Butyllithium at -78 °C. It has also been converted to its sodium and potassium salts with the corresponding alkali metal amides.4 The lithiated species is a useful nucleophilic carboxylating reagent for a variety of organic electrophiles. This chemistry is discussed in the article Tris(phenylthio)methyllithium.

Electrophilic Formylation.

Apart from its role as precursor to tris(phenylthio)methyllithium, the utility of the reagent in organic synthesis has been very limited. Its use as an aromatic electrophilic formylating agent stems from the ability of certain Lewis acids to generate the bis(phenylthionium) cation (1) (eq 1).1 In the case of intermolecular aromatic formylation, Dimethyl(methylthio)sulfonium Tetrafluoroborate (DMSTF)5 is most effective in promoting the reaction. Yields of aldehydes are in the range 35-85%. The best yields are obtained with polycyclic aromatics such as a- or b-naphthol, although more-functionalized substrates still give acceptable results (eq 2). The hydrolysis of the thioacetal by excess DMSTF completes the sequence.

The scope of the substitution is limited to oxygen-activated aromatics. With these substrates there is a pronounced preference for formylation at the para position if it is available. If the para position is blocked, ortho formylation occurs with yields approximately equal to para formylation. Unactivated or weakly activated aromatics such as benzene or alkylbenzenes do not react with the reagent. Nitrogen-activated aromatics effectively compete with the reagent for the Lewis acid and are thus unable to react.

An extension of this chemistry has been developed for the preparation of cyclic oxygenated a-keto aromatics such as the methoxy-a-tetralone (2).6 When applied in the intramolecular sense, the scope of the reaction broadens somewhat to include some alkyl-substituted substrates (for six-membered annulation). Annulation of five- or seven-membered rings onto the aromatic nucleus still requires oxygen activation. Although DMSTF was effective in promoting closure in some cases, Silver(I) Trifluoromethanesulfonate in methylene chloride proved to be a more generally effective catalyst for this reaction (eq 3).

In the case of diazo esters, Boron Trifluoride Etherate was shown to promote formylation (eq 4).3

1. (a) Seebach, D. AG(E) 1967, 6, 442. (b) Seebach, D. AG 1967, 79, 468. (c) Seebach, D. CB 1972, 105, 487 (CA 1972, 76, 99 736).
2. Smith, R. A. J.; Manas, A. R. B. S 1984, 166.
3. Schönberg, A.; Praefcke, K. CB 1966, 99, 2371 (CA 1966, 65, 8752).
4. Fröling, A.; Arens, J. F.; RTC 1962, 81, 1009.
5. Trost, B. M.; Murayama, E. JACS 1981, 103, 6529.
6. Manas, A. R. B.; Smith, R. A. J. T 1987, 43, 1847.

Conrad Santini

Merck Research Laboratories, Rahway, NJ, USA

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