A Versatile Approach to Dynamic Amide Bond Formation with Imine Nucleophiles

Abstract

Dynamic covalent chemistry has rapidly become an important approach to access supramolecular structures. While the products generated in these reactions are held together by covalent bonds, the reversible nature of the transformations can limit the utility of many these systems in creating robust materials. We describe herein a method to form stable and commonly employed amide bonds by exploiting the reversible coupling of imines and acyl chlorides. The reaction employs easily accessible reagents, is dynamic under ambient conditions, without catalysts, and can be trapped with simple hydrolysis. This offers an approach to create broad families of amide products under thermodynamic control, including the selective formation of amide macrocycles or polymers.

Keywords: amide synthesis; dynamic covalent chemistry; iminium salts; macrocycles; organic synthesis.