Weiwei Luo

Asymmetric Synthesis of β‐Amino Nitriles through a ScIII‐Catalyzed Three‐Component Mannich Reaction of Silyl Ketene Imines

Chiral b-amino nitriles are versatile synthetic intermediates that are readily transformed into optically active compounds such as b-amino acids, and 1,3-diamines. The asymmetric addition of alkyl nitriles to imines provides a straightforward route to such compounds. Although many methods for the asymmetric Mannich reaction have been described, the use of less nucleophilic alkyl nitriles as the nitrile species is a continuing challenge; one reason for this issue is the poor acidity of the a protons of alkyl nitriles. One strategy to solve this problem is the use of an N-metalloketene imine, generated from cyanocarboxylic acid or benzyl nitrile, as an active intermediate; two catalytic asymmetric systems have been reported for such Mannich reactions. As an alkyl nitrile equivalent, silyl ketene imines (SKIs) are competent nucleophiles that can react to form C-substituted nitriles (Scheme 1). Moreover, owing to their unique structure and