Methyl p-Toluenethiosulfonate1

[4973-66-4]  · C8H10O2S2  · Methyl p-Toluenethiosulfonate  · (MW 202.32)

(methylsulfenylating agent for formation of useful intermediates which have many applications)

Alternate Name: methyl thiotosylate.

Physical Data: mp 58 °C.

Form Supplied in: white solid.

Preparative Method: prepared by methylation of sodium p-toluenethiosulfonate with Dimethyl Sulfate (65%).2

Optically Active Methyl Sulfoxide Derived from Camphor.

(+)-Camphor is converted by methylsulfenylation of the lithium enolate with methyl p-toluenethiosulfonate (MeSTs) into exo-3-(methylthio)camphor, which upon reduction with Diisobutylaluminum Hydride gives the corresponding exo-(methylthio)isoborneol. Oxidation of the sulfide with m-Chloroperbenzoic Acid gives optically pure exo-3-(methylsulfinyl)isoborneol (eq 1).3

Interestingly, use of excess Lithium Diisopropylamide and Hexamethylphosphoric Triamide allows exclusively thermodynamic endo-3-(methylthio)camphor formation. The alternative methylsulfenylating agent Dimethyl Disulfide is not suitable for this highly stereoselective transformation since it gives a mixture of exo/endo sulfides in low yield. The method is elaborated for use of allyl p-toluenethiosulfonates which furnish optically pure exo-3-(allylsulfinyl)isoborneols. The derived dianions of these isoborneols undergo diastereoselective conjugate addition reactions with cyclopentenones.4

Beckmann Fragmentation of a-Methylsulfenyl Oximes.

It is known that a second-order Beckmann fragmentation is favored by introduction of a methylsulfenyl group a to the oxime group.5 The termini of the bond that is cleaved are obtained in different oxidation states which can be manipulated for further functionalization. MeSTs is used to prepare an a-methylthio ketone, a precursor to the oxime for the fragmentation. An application of this fragmentation is exemplified by a conversion of a cyclohexanone into a d-valerolactone (eq 2).6

a-Keto Aldehyde from a-(Methylsulfenyl)methyl Ketone.

A two-step conversion of a methyl ketone to an a-keto dimethyl acetal via methylsulfenylation with MeSTs, followed by oxidation with N-Chlorosuccinimide has been described (eq 3).7

Efficient Synthesis of Cardenolides.

A general and efficient method has been described for the synthesis of cardenolides, consisting of (1) a-methylsulfenylation of pregnen-20-one, (2) Reformatsky reaction, and (3) butenolide formation by alumina chromatography of the epoxy ester obtained from the S-methylated Reformatsky product (eq 4).8

Related Reagents.

Dimethyl Disulfide; Methyl Methanethiosulfonate.

1. Trost, B. M. CRV 1978, 78, 363.
2. Gibson, D. T. JCS 1931, 2637.
3. Goodridge, R. J.; Hambley, T. W.; Haynes, R. K.; Ridley, D. D. JOC 1988, 53, 2881.
4. Binns, M. R.; Goodridge, R. J.; Haynes, R. K.; Ridley, D. D. TL 1985, 26, 6381.
5. (a) Autrey, R. L.; Scullard, P. W. JACS 1968, 90, 4917, 4924. (b) Shimizu, Y. TL 1972, 2919.
6. (a) Grieco, P. A.; Hiroi, K. TL 1973, 1831. (b) Grieco, P. A.; Hiroi, K.; Reap, J. J.; Noguez, J. A. JOC 1975, 40, 1450.
7. Yoshii, E.; Miwa, T.; Koizumi, T.; Kitatsuji, E. CPB 1975, 23, 462.
8. Yoshii, E.; Koizumi, T.; Ikeshima, H.; Ozaki, K.; Hayashi, I. CPB 1975, 23, 2496.

Kumiko Takeuchi

Eli Lilly and Company, Indianapolis, IN, USA

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