Electrophilic methylthiomethylation of enol ethers and activated aromatic compounds. Application of the former reaction to the synthesis of the macrocycle, 3,3,7,7,11,11,15,15-octamethyl-1,9-dithia-5,13-diaza-cyclohexadecane

Abstract

Enol ethers of dialkylacetaldehydes, either as such, or generated in situ from the corresponding acetals, undergo ready methylthiomethylation when heated with dimethyl sulphoxide–acetic anhydride (or methylthiomethyl acetate) in the presence of boron trifluoride–diethyl ether. These same reagent combinations can be used to methylthio-methylate certain activated aromatic compounds. The synthetic utility of the former reaction is demonstrated in the synthesis of 2,2,6,6-dimethyl-4-thiaheptanedial (4) which has been converted into 3,3,7,7,11,11,15,15-octamethyl-1,9-dithia-5,13-diazacyclohexadecane (7).