Rational Design of Amine Nucleophiles for Dynamic Kinetic Resolution of Azlactones Leading to Highly Enantioselective Synthesis of Bisamides

Abstract

AbstractThe first catalytic asymmetric aminolysis of azlactones was achieved, enabling the highly enantioselective dynamic kinetic resolution of azlactones. This was demonstrated to be an efficient method for synthesizing optically pure bisamides in high yield with excellent enantioselectivity (up to 99 % yield, 99 % ee). The rational design of the amine nucleophile bearing both a sterically bulky group and an activating group was shown to be a key factor in attaining excellent enantioselectivity in the catalytic asymmetric aminolysis of azlactones. This approach not only provides easy access to biologically important enantiopure bisamides, but also enables the dynamic kinetic resolution of azlactones by using a strategy of enantioselective aminolysis, which was previously unknown in this research field.