Mechanistic studies of diastereoselective cyclopropanations of homochiral ene-ketals and synthesis and resolution of diastereomeric alpha-hydroxycycloalkanone ketals.

Abstract

A series of homochiral ene ketals were prepared and subjected to the Simmons-Smith cyclopropanation. A mechanistic model was formulated to explain the observed diastereoselectivity seen for the common ring systems. Diastereoselectivity is thought to result from preferential chelation of the Simmons-Smith reagent at the least sterically hindered lone pair of electrons on the dioxolane oxygen proximal to the alkene. The role of dioxolane oxygen was inferred from studies with a hydrocarbon model system. The effect of cyclohexene ring conformation on the diastereoselectivity was examined for conformationally restricted ene ketal systems. Reagent chelation by the pseudoequatorial dioxolane oxygen atom was shown to be favored. This preference can either antagonize or reinforce diastereoselectivity due to steric hindrance of the dioxolane oxygen atoms from dissymmetric placement of the appendages on the dioxolane ring. A general method for the chromatographic resolution of diastereomeric α-hydroxycycloalkanone ketals derived from 1,4-di-O-benzyl-L-threitol is reported. Separability is thought to result from differences in intramolecular hydrogen bonding for the two diastereomeric forms.