Asymmetric synthesis of epoxides from aldehydes mediated by (+)-(2R,5R)-2,5-dimethylthiolane

Abstract

Nonracemic epoxides were prepared by reaction of (+)-(2R,5R)-2,5-dimethylthiolane, benzyl bromide and a mineral base with an aldehyde. Various parameters (solvent, base, aldehyde, sulfide) have been investigated. These studies led to the optimisation of a practical and simple procedure. Acetonitrile or tert-butyl alcohol were used in the presence of water and potassium or sodium hydroxide at room temperature. These conditions gave 87–93% yields with aromatic or branched aliphatic aldehydes and enantiomeric excesses ranged from 66 to 96%. Kinetic studies and stereochemical analyses have been carried out and a transition state was suggested to rationalize the observed stereochemistry.