Regiospecificity of methylation of unsymmetrical stilbenes by methylsulphinylmethanide

Abstract

Treatment of (E)-2-methylstilbene with methylsulphinylmethanide (DMSO^–) for short periods produces a mixture of α′,2-dimethylstilbene (6)(>95%E-) and methyl 3-phenyl-2-(o-tolyl)propyl sulphoxide (22), from which (6) can be separated in ca. 50% yield. Longer periods of reaction give a 4 : 5 mixture of α,2-dimethylstilbene [(10)+(11)] and methyl 3-phenyl-4-(o-tolyl)butyl sulphoxide (29). (Z)-2-Methylstilbene gives identical products with DMSO^– under similar conditions. Convenient syntheses of the Z- and E-isomers of α,2- and α′,2-dimethylstilbenes [(6), (7), (10), and (11)] and of the methyl 2-phenyl-3-(o-tolyl)propyl sulphoxides (21) and (22) are reported, and studies of their reactions with DMSO^– are described. The reaction of the sulphoxide (22) with DMSO^– produces a 2 : 1 mixture of (10) and (11) exclusively, whereas a similar reaction of the isomeric sulphoxide (21) gives a mixture of the stilbene (6) and the butyl sulphoxide (29), the proportion varying with the time of reaction; long periods of reaction between (21) and DMSO^– give only (29). The sulphoxide (29) also results from the reaction of (6) and 2-phenyl-3-(o-tolyl)propene (36) with DMSO^–. By contrast α,2-dimethylstilbene does not react further with DMSO^–. The α-(α′-)methylation process by DMSO^– is rationalised in terms of a nucleophilic addition–prototropic shift–β-elimination–isomerisation sequence, and an explanation for the ‘apparent’ regiospecificity of α- and α′-methylation of 2-methylstilbene under the different reaction conditions is presented.

Methylation of the 2,6-dimethylstilbene (41) with DMSO^– is almost totally (>95%) regiospecific and produces largely the α-methylstilbene products [(42)+(43)] and the α-sulphoxide (52); < 1%α′-methylstilbene (47) was produced. The 2,2′,6,6′-tetramethylstilbene (59) does not react with DMSO^–.