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Updated: Jun 2, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Enantioselective gem-chlorofluorination of active methylene compounds using a chiral spiro oxazoline ligand
Kazutaka Shibatomi1, Akira Narayama, Yoshinori Soga
1Department of Environmental and Life Sciences, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Japan. shiba@ens.tut.ac.jp
Abstract:
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 α-chloro-α-fluoro-β-keto esters and α-chloro-α-fluoro-β-keto phosphonates with up to 92% ee. The resulting dihalo β-keto ester was converted into various α-fluoro-α-heteroatom-substituted carbonyl compounds via nucleophilic substitution without loss of optical purity. A fully protected β-amino acid with a gem-chlorofluoromethylene function was also synthesized.
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