Catalyst-Free, Three-Component Synthesis of Amidinomaleimides

J Org Chem. 2024 Sep 20;89(18):13756-13761. doi: 10.1021/acs.joc.4c01485. Epub 2024 Aug 23.

Abstract

Maleimide and amidine functionalities often appear in medicinal and natural product targets. We describe a catalyst-free, three-component coupling reaction for the synthesis of amidinomaleimides. This one-pot reaction fuses a broad range of secondary amines and aldehydes with azidomaleimides. The conditions are mild, simple, modular, high yielding, and amenable to aqueous solvents. Most reaction products can be sufficiently purified without column chromatography. The synthesis creates complex, multifunctional molecules with four different molecules, including a tripeptide, arrayed around an amidinomaleimide core.