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

Coordinated benzonitrile in cis-[PtCl2((RMeSO)-Me-3)(PhCN)] (R-3 = Me, Ph) is sufficiently activated to undergo [2 + 3] cycloaddition with nitrones -O+N(R-2)=CH(R-1) (R-1 = Ph, p-C6H4Me, p-C6H4OMe, R-2 = Me; R-1 = Ph. R-2 = CH2Ph) under mild conditions to give the corresponding Delta (4)-1.2.4-oxadiazoline complexes cis-[PtCl2((RMeSO)-Me-3)- {N=C(Ph)-ON(R-2)-CH(R-1)}] in 68-83% yield. In this reaction, the chiral sulfaxide in cis-[PtCl2(PhMeSO)(PhCN)] induces stereoselective formation of the coordinated Delta (4)-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) {N=C(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((RMeSO)-Me-3) {N=C(Ph)-ON(R-2)-CH(R-1)}] with ethane- 1.2-diamine results in displacement of the Delta (4)-1,2,4-oxadiazolines from the metal and concomitant formation of water-soluble [Pt(en)(2)]Cl-2 and sulfoxide. which can both be removed by aqueous extraction, and this allows for the first time the isolation of Delta (4)-1.2.4-oxadiazolines in enantiomerically enriched form. Applying this technique to cis-(R-S,S-C,)_[PtCl2(PhMeSO)- {N=C(Ph)- ON(Me)- C(H)Ph}] of 90% d.e. and 79% e.e. in sulfoxide. the corresponding (R)-2-methyl-3.5-diphenyl- Delta (4)-1,2.4-oxadiazo line was obtained with 70% e.e.