Electrochemical Post-Ugi Cyclization for the Synthesis of Highly Functionalized Spirolactams

J Org Chem. 2023 Oct 6;88(19):13977-13994. doi: 10.1021/acs.joc.3c01532. Epub 2023 Sep 11.

Abstract

The combination of the Ugi reaction and electro-organic synthesis can aid in the creation of novel heterocycles that have not been previously explored. In this study, a new strategy utilizing bis-amides from the Ugi reaction has been developed, which can produce C-S, C-Se, and C-C═O functionalized five-membered spirolactams mediated by electricity under catalyst- and metal-free conditions. Notably, this approach can be applied using a microelectro-flow reactor (μ-EFR) for gram-scale synthesis. The described strategy can synthesize complex azaspiro-fused tricyclic scaffolds with high diastereo- and regioselectivity, highlighting its versatility and potential.