Award Lecture Paper: Nickel-Catalyzed N-Arylation of Optically Pure Amino Acid Esters with Activated (Hetero)aryl Electrophiles

An efficient method for the C–N cross-coupling of (hetero)aryl (pseudo)halides with optically pure α-amino acid esters employing a commercially available nickel catalyst and weak inorganic base was developed. This is the first example of Ni-catalyzed N-arylation of amino acid esters without the use of electrochemistry, which was shown to effectively couple a variety of amino acid tert-butyl esters with (hetero)aryl chlorides, bromides, and tosylates in high yields and excellent enantioretention. Base-mediated racemization was revealed during control experiments, but increasing the steric bulk of the amino acid ester group limited the amount of racemization of the product.