Highly stereoselective synthesis of the anti-platelet activating factor, 4-thiazolidinones, using silyl derivatives of 2-mercaptoalkanoic acids

Article abstract of DOI:10.1246/bcsj.68.1467

The cyclo-condensation of silyl 2-mercaptoalkanoates and arylmethyleneamines proceeded with high stereoselectivity to give alternatively both the cis- and trans-2,5-disubstituted 4-thiazolidinones, some of which are known as anti-platelet activating factor-active drugs. The use of the piperidine catalyst and no catalyst showed very high cis-stereoselectivity (cis/trans=10/1-50/1) during the reaction. On the other hand, the trans-selective reaction was promoted by Ti(O-i-Bu)₄ and Al(O-s-Bu)₃ catalysts (cis/trans=1/8-1/25). Both reactions were conducted with higher cis- and trans-selectivities as compared with those of the alkyl 2-mercaptoalkanoates under mild conditions. The cyclo-condensation using trimethylsilyl 2-(trimethylsilylthio)propionate and methyl 2-(trialkylsilylthio)propionates proceeded by the action of a catalytic amount (0.02 molar amount) of tetrabutylammonium fluoride with moderate cis-selectivity.