Zinc p-Toluenesulfonate

[13438-45-4]  · C14H14O6S2Zn  · Zinc p-Toluenesulfonate  · (MW 407.81) (.6H2O)

[60553-56-2] (.xH2O; hydrate)


(agent for tosylation1 under mild Mitsunobu conditions, usually with inversion)

Alternate Name: zinc tosylate.

Solubility: insol H2O, benzene.

Form Supplied in: white solid; the hydrate is commercially available.

Preparative Method: anhydrous material1 is prepared when the precipitate formed from mixture of p-Toluenesulfonic Acid and Zinc Chloride in water is filtered off and dried in vacuo at rt for 1 h. Purification is not usually required.

Handling, Storage, and Precautions: no unusual precautions are noted, but storage in a well stoppered container is advisable.

Tosylate Formation with Inversion of Configuration.

Alkyl tosylates can be formed directly from secondary alcohol functionality with retention of carbon stereochemistry by treatment with p-Toluenesulfonyl Chloride and Pyridine. However, conversion of an alcohol to the corresponding tosylate of opposite stereochemistry typically requires a minimum of three steps. For example, inversion of the stereocenter with benzoic acid under Mitsunobu reaction conditions, hydrolysis of the resulting ester, and finally conventional tosylation of the alcohol, provides an attractive route for this transformation.2 A similar route, the inversion of a secondary alcohol directly with p-TsOH, Diethyl Azodicarboxylate (DEAD), and Triphenylphosphine, does not produce the desired tosylate product.1

Modification of this procedure, through the use of bis(p-toluenesulfonato)zinc ((p-TsO)2Zn) with Mitsunobu conditions, allows this transformation to proceed in a single step.1 Although somewhat slower than the analogous inversion with benzoic acid, treatment of secondary alcohols with (p-TsO)2Zn, DEAD, and Ph3P gives the desired tosylate product in high yield. This reaction is effective for tosylate formation from either acyclic or cyclic secondary alcohols with clean inversion of stereochemistry (eq 1). As expected, this reaction is very sensitive to the steric hindrance at the reacting sp3 center; moderately hindered alcohols, e.g. (1), require longer reaction times and greater quantities of DEAD and Ph3P to undergo the transformation in high yield (eq 2). Similarly, the use of p-TsOLi is effective for this transformation, but yields are slightly lower than those obtained with (p-TsO)2Zn.

Tosylation with Retention of Stereochemistry.1

Although dihydrocholesterol (2) undergoes clean tosylation with inversion in 88% yield using the procedure described above, cholesterol (3a) itself gives an 85% yield of the 3b-tosylate (3b).

It was suggested that this anomaly could be explained by the intermediacy of a cyclopropylmethyl/homoallylic species, trapped by addition of tosylate ion. Indeed, the more vigorous Mitsunobu reaction2 of (3a) with benzoic acid leads to a mixture of four products, confirming involvement of this type of homoallylic rearrangement.

Although anomalous, it is conceivable that this Mitsunobu procedure could be of use in effecting tosylation with retention in less common systems in which neighboring group effects, for example, override the normal stereochemical outcome.

1. Galynker, I.; Still, W. C. TL 1982, 23, 4461.
2. (a) Mitsunobu, O.; Eguchi, M. BCJ 1971, 44, 3427. (b) Mitsunobu, O. S 1981, 1.
3. Keinan, E.; Sinha, S. C.; Sinha-Bagchi, A. JOC 1992, 57, 3631.
4. Ager, D. J.; East, M. B. T 1992, 48, 2803.

Peter Ham

SmithKline Beecham Pharmaceuticals, Harlow, UK

John R. Stille

Michigan State University, East Lansing, MI, USA

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