A NOVEL PALLADIUM-CATALYZED ASYMMETRIC CYCLOCARBONYLATION OF ALLYLIC ALCOHOLS TO GAMMA-BUTYROLACTONES

A catalyst system based on [Pd-2(dba)(3)]. CHCl3/(-)-BPPM has been fou nd to effect asymmetric cyclocarbonylation of certain prochiral allyli c alcohols to produce good yields of optically enriched gamma-butyrola ctones. The reaction was performed under an atmosphere of H-2 (400 psi ) and CO (400 psi) at 100 degrees C in methylene chloride for 48 hours . Asymmetric cyclocarbonylation of allylic alcohols with aliphatic sub stituents proceeded with moderate enantioselectivities (ee = 25-43%). However, enantiomeric excesses of up to 83% were obtained for substrat es containing aromatic substituents, in which case the ee was found to be more sensitive to steric, rather than to electronic factors. Recry stallization of the lactones containing an aromatic group from a mixtu re of CH2Cl2/Et2O/hexanes (0.5/1.0/8.5), by slow evaporation of the so lvent or at low temperature, improved the enantiopurities to >98% ee o n a reproducible basis. The asymmetric center of the aromatic lactones was assigned the (S)-configuration based on the X-ray crystal structu re analysis of enantiopure 3-dimethyl-2-(2'-methylphenyl)-gamma-butyro lactone (2k). A hydridopalladium um intermediate is believed to play a key role in this reaction. Enantioselectivity is thought to be brough t about by the preferential formation of 6b. The carbon skeleton of 6b fits into the chiral scaffold of(-)-BPPM.