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-(R_S,S_C)-[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.