Diastereoselective palladium-catalyzed C(sp3)–H cyanomethylation of amino acid and carboxylic acid derivatives

Abstract

In this study, we report an efficient protocol for Pd-catalyzed methylene β-C(sp³)–H cyanomethylation of 8-aminoquinoline-directed α-amino acids using inexpensive chloroacetonitrile. Iodoacetonitrile generated in situ from chloroacetonitrile reacts with methylene C(sp³)–H bonds of α-amino acids with excellent diastereoselectivity, enabling access to a wide range of important γ-cyano-α-amino acids. Our protocol works well with different amino acid and carboxylic acid derivatives with good chemical yields and high functional group tolerance.