[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
(+)-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
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 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
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
Eli Lilly and Company, Indianapolis, IN, USA