New Synthetic Approach to 1-Fluorocyclopropane Derivatives
Cyclopropane derivatives have attracted considerable attention as important pharmacophores. The conjugate addition of stabilized sulfonium ylides to a,b-unsaturated ketones and esters to give cyclopropane-1-carboxylate derivatives with high diastereo- and enantioselectivity has been extensively studied in both catalytic and stoichiometric modes. Despite these advances, preparation of functionalized 1-fluorocyclopropane-1-carboxylate derivatives remains a significant and daunting challenge.
Herein we would like to present a convenient one-pot synthesis of fluorocyclopropanes wherein the cyclopropane moiety is assembled using by a modified conjugate addition with a fluorinated sulfonium ylide. The cyclopropanation is achieved using an novel fluoro-substituted ethyl-(dimethylsulfuranylidene)-acetate generated in situ from the corresponding ylide and a fluorinating reagent in THF at -78ºC.