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Updated: Jul 9, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Cobalt(II)-Catalyzed Selective Three-Component Oxyalkylation of N-Aryl Glycinates: A Route to CF3-Labeled Threonine
Yadong Li1, Dengfu Lu1,2, Yuefa Gong1
1Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, Hubei, China.
Abstract:
Glycinates, protected enols, and an electrophilic trifluoromethylating reagent were employed to assemble CF3-labeled threonine analogues through a radical addition cascade. To suppress the competing oxidation of the oxyalkyl radical intermediate, various redox catalysts were evaluated and Co(II) exhibited supreme selectivity control with a proper counterion. A series of glycinate and related peptides were thus successfully modified under Co-catalysis. Mechanistic studies revealed that a N-aryl glycinate could be preferentially oxidized by cobalt over the oxyalkyl radical to generate an imine intermediate, and the key to this selectivity could be ascribed to the prechelation of glycinate, as well as a weakly basic carboxylate counterion.
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