Enantioselective Synthesis of Arylglycines via Pd-Catalyzed Coupling of Sch?llkopf Bis-Lactim Ethers with Aryl Chlorides

Arylglycines are important pharmacophores present in several top-selling drugs. This compound class has now been made accessible from abundant aryl chlorides by a Pd-catalyzed Schollkopf-type amino acid synthesis. In the presence of the catalyst methyl-naphthyl(XPhos)-palladium bromide, the base lithium 2,2,6,6-tetramethylpyrrolidide and the additive ZnCl2, tert-leucine-derived bis-lactim ethers were efficiently arylated at room temperature, reaching yields of 95 % and diastereoselectivities of 98 : 2. Hydrolysis gave the corresponding arylglycines in high enantiomeric excess.