Cobalt(II)-Catalyzed Selective Three-Component Oxyalkylation of N-Aryl Glycinates: A Route to CF3-Labeled Threonine Analogues.

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.