Synthesis of bridgehead-azacycles via dual C-N/C-C annulation of α-amino acids, aminals and maleimides

The synthesis of various bridged azacyclic adducts has recently become a reemerging topic due to their bioactive and natural product mimic profiles. Accordingly, herein, we report a method for easy access to succinamide-bridged azacyclic derivatives through the metal-free polarization-controlled dual C-N/C-C annulation of readily available alpha-amino acids, 2-amino benzaldehydes or pyrrole/indole-2-aldehyde and maleimide substrates. This cascade features a rare dipolarophile-induced diastereo-selective amidative annulation, followed by 3 + 2 cycloaddition as key steps.

Automated summary

The synthesis of various bridged azacyclic adducts is an important topic due to their bioactive and natural product mimic profiles. In this study, a method for the easy access to succinamide-bridged azacyclic derivatives through a metal-free polarization-controlled dual C-N/C-C annulation is reported.