Studies on stereoselective epoxidation of sulfur ylide and its applications to organic synthesis

Abstract

Epoxides are versatile tools for organic synthesis and stereoselective syntheses of them are attracting much attention. We investigated various solvent effects on the diastereoselectivity in the sulfur ylide mediated epoxidation reaction under salt free condition and proved that diastereoselectivity is influenced by solvating power of solvents. Moreover, it was found that protic solvents reduce diastereoselectivity. This is believed that in protic solvents, both betaines generated from the reaction of ylide and aldehyde are strongly stabilized through hydrogen bonding resulting in deceleration of reverse process to ylide and aldehyde. We also developed a new epoxidation process using chiral sulfonium salt. Chiral sulfonium salts can be generated from the corresponding bromide or alcohol. Epoxidation reactions were successful for most substrates including heteroaromatic aldehydes and ketones, which are not available in the catalytic cycle and chiral sulfide was recovered almost quantitatively and reused without loss of selectivity. On the basis of this progress, we successfully synthesized CDP-840, a candidate drug for asthma in enantiomerically pure form, Prelactone B, highly functionalized naturally occurring S-lactone, and S-lactone moiety in mevinic acid, which is known to have biological activity to lower cholesterol level in serum.