Enantioselective gem-Chlorofluorination of Active Methylene Compounds Using a Chiral Spiro Oxazoline Ligand

Highly enantioselective gem-chlorofluorination of active methylene compounds was carried out by using a copper(II) complex of a chiral spiro pyridyl monooxazoline ligand. This reaction yielded alpha-chloro-alpha-fluoro-beta-keto esters and alpha-chloro-alpha-fluoro-beta-keto phosphonates with up to 92% ee. The resulting dihalo beta-keto ester was converted into various alpha-fluoro-alpha-heteroatom-substituted carbonyl compounds via nucleophilic substitution without loss of optical purity. A fully protected beta-amino acid with a gem-chlorofluoromethylene function was also synthesized.