Palladium-mediated asymmetric synthesis of 3β,5β,7β-trihydroxycycloheptene derivatives

Article abstract of DOI:10.1016/S0040-4020(97)00238-X

Asymmetric alkylation of 3,5,7-trihydroxycycloheptene derivative 15 was developed using a palladium catalyst with chiral ligand. The reaction site of π-allylpalladium complex 18 is controlled by steric repulsion between the nuclcophile and the substituents on the cycloheptene ring. When 15b was reacted with lithium dimethyl malonate using a catalytic amount of [Pd(C₃H₅)Cl]₂ in the presence of (S)-BINAPO in THF, alkylated product 17 was obtained in 71% yield with 42% ee. However, the reaction of 15b with a large nucleophile, diethyl 2-lithio-2-(2-propenyl)malonate, in the presence of [Pd(C₃H₅)Cl]₂ and (S)-BINAP in THF gave alkylated product 21d in 41% yield with 94% ee. In a similar manner, the reaction of 15b with dimethyl 2-(3-butenyl)-2-lithiomalonate 5e gave 21e in 64% yield with 82% ee.