Access to Unnatural Enantioenriched Amino Acids Derived from Phenylglycine through Nickel-Catalyzed Suzuki–Miyaura Coupling Involving Carbon–Oxygen Bond Insertion

We report herein the optimization of a nickel-catalyzed Suzuki–Miyaura coupling for the synthesis of unnatural bi- and polyaryl and heteroaryl amino acid derivatives (28 examples). The aim is to provide an inexpensive and efficient alternative to palladium-catalyzed reactions, exploiting nickel’s reactivity toward oxygen-based electrophiles. To this end, easily racemizable hydroxyphenylglycine derivatives are used. The reaction involves an air-stable nickel precatalyst in association with an electron-rich phosphine and potassium carbonate under water-free conditions, to ensure the highest enantiomeric purities and conversions.