Enantiopure-fused azetidines, the privileged structural motifs, are widespread in natural products and medically relevant molecules. It's important to develop efficient catalytic systems for the rapid assembly of such important frameworks.
Recently, a research team led by Prof. CHEN Qing'an from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) has developed a chiral phosphoric acid (CPA) catalyzed multicomponent reaction of anilines, aldehydes, and azetidinones to access tetrahydroquinoline-fused azetidines with three contiguous stereocenters.
Their findings were published in Chem Catalysis on June 20.
In this work, the researchers developed the chiral phosphoric acid (CPA) catalysis using commercially available anilines, benzaldehydes, and azetidinones as starting materials. This protocol enabled the one-step construction of three contiguous stereocenters with high diastereo- and enantioselectivities.
DFT calculations implied that a stepwise mechanism consisting of enamine-imine addition and Friedel-Crafts attack is likely involved.
"This work not only provides an efficient alternative to access chiral fused azetidines, but also opens up an avenue to design other asymmetric multicomponent reaction," said Prof. CHEN.
The research was supported by Dalian Outstanding Young Scientific Talent, and the National Natural Science Foundation of China. (Text by HU Yancheng)