Stereoselective [2 + 3] cycloaddition of nitrones to platinum-bound organonitriles. First enantioselective synthesis of Δ4-1,2,4-oxadiazolines†

Abstract

Coordinated benzonitrile in cis-[PtCl2(R3MeSO)(PhCN)] (R3 = Me, Ph) is sufficiently activated to undergo [2 + 3] cycloaddition with nitrones −O+N(R2)CH(R1) (R1 = Ph, p-C6H4Me, p-C6H4OMe, R2 = Me; R1 = Ph, R2 = CH2Ph) under mild conditions to give the corresponding Δ4-1,2,4-oxadiazoline complexes cis-[PtCl2(R3MeSO){NC(Ph)–ON(R2)–CH(R1)}] in 68–83% yield. In this reaction, the chiral sulfoxide in cis-[PtCl2(PhMeSO)(PhCN)] induces stereoselective formation of the coordinated Δ4-1,2,4-oxadiazoline leading to mixtures of diastereomeric platinum complexes with a d.e. of 30–60%, which can be enhanced to >90% by fractional crystallization. The major diastereoisomer of [PtCl2(PhMeSO){NC(Ph)–ON(Me)–C(H)Ph}] thus obtained was analyzed by X-ray diffraction and shown to have cis-(R,S) configuration.Reaction of cis-[PtCl2(R3MeSO){NC(Ph)–ON(R2)–CH(R1)}] with ethane-1,2-diamine results in displacement of the Δ4-1,2,4-oxadiazolines from the metal and concomitant formation of water-soluble [Pt(en)2]Cl2 and sulfoxide, which can both be removed by aqueous extraction, and this allows for the first time the isolation of Δ4-1,2,4-oxadiazolines in enantiomerically enriched form. Applying this technique to cis-(RS,SC)-[PtCl2(PhMeSO){NC(Ph)–ON(Me)–C(H)Ph}] of 90% d.e. and 79% e.e. in sulfoxide, the corresponding (R)-2-methyl-3,5-diphenyl-Δ4-1,2,4-oxadiazoline was obtained with 70% e.e.