The role of fluorine-containing methyl groups toward diastereofacial selection

Abstract

Michael addition reactions of various enolates derived from the selected ketone, ester, and amide toward γ-CH3-nFn-α, β-unsaturated ketones (n=1∼3) were proved to smoothly furnish the desired 1, 4-adducts with the high level of si face selectivity which monotonously decreased by reduction of a number of fluorine. Although the Felkin-Anh model correctly anticipates the present stereochemical outcome only when E-acceptors were employed and the opposite stereoisomer was obtained from the corresponding trifluorinated Z-isomer, the hyperconjugative stabilization of transition states by electron donation from the allylic substituents (the Cieplak rule) successfully explains the π-facial preference of both E- and Z-acceptors at least in a qualitative manner.