Synthesis of chiral diferrocenyl dichalcogenides and their application to asymmetric nucleophilic ring opening of meso-epoxides

Abstract

Four novel optically active bis[(R,S)- and (S,R)-2-(1-dimethylaminoethyl)ferrocenyl] dichalcogenides [abbreviated as (R,S)- and (S,R)-(Fc*E)2(E = S and Te)], each of which possesses two axial and two central elements of chirality, have been prepared by lithiation of commercially available chiral (1-dimethylaminoethyl)ferrocenes, followed by treatment with elemental sulfur or tellurium and air oxidation, in 42–65% isolated yields. The structure of the di-(S,R)-ferrocenyl disulfide has been fully characterized by X-ray crystallography. Ferrocenyl chalcogenide anions (Fc*E–) produced by reduction of the above (Fc*E)2 and the known (Fc*Se)2 with LiAlH4 in tetrahydrofuran are found to act as useful stereoselective nucleophiles for ring opening of meso-epoxides such as cyclohexene oxide, cyclopentene oxide, cyclooctene oxide and cis-stilbene oxide to give the corresponding ferrocenyl β-hydroxyalkyl chalcogenides in high yields with up to 71% diastereoisomeric excess (de). Although the diastereoselectivity depends on the combination of chalcogen atom and meso-epoxide, it is generally higher with E = S and Se than with E = Te. Selenoxide elimination of (S,R)-2-(1-dimethylaminoethyl)ferrocenyl 2-hydroxycyclohexyl selenide (66% de), obtained by the ring opening of cyclohexene oxide with (S,R)-(Fc*Se)2, gives (S)-cyclohex-2-enol with 60% ee. The S-configuration suggests that the ring opening, by the nucleophilic attack of the chiral ferrocenyl chalcogenide anion on the epoxide carbon, mainly occurs via the least hindered transition state considering the interactions between the epoxide, the 1-dimethylaminoethyl moiety and the ferrocene.