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 [alpha]-amino acid esters employing a commercially available nickel catalyst and weak inorganic base was developed. This is the first example of Nicatalyzed 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. Key words: amination, cross-coupling, amino acid esters, nickel
Introduction Transition metal catalysis is widely employed for cross-coupling reactions in modern synthetic organic chemistry, enabling the development of complex molecules from readily available starting materials. The development of catalysts [...]