Efficient amide bond formation via tropylium ion organocatalysis

Abstract

Amide bond formation is a fundamental reaction in organic synthesis, essential for the construction of peptides and various bioactive molecules. Traditional methods for amide bond formation often require harsh conditions, expensive reagents, or generate undesirable by-products. Herein, we report a novel and efficient method for amide bond formation utilizing tropylium ion organocatalysis. The tropylium ion, known for its stability and unique electronic properties, facilitates the activation of carboxylic acids and amines, promoting their coupling under mild conditions. This method demonstrates high yields and broad substrate scope, including sterically hindered and functionalized reactants. The mechanistic studies suggest that the tropylium ion acts as an electrophilic catalyst, enhancing the nucleophilicity of the amine and the electrophilicity of the carboxylic acid, thereby accelerating the formation of the amide bond. This work opens new avenues for the development of green and sustainable catalytic processes in organic synthesis. In order to explore the effect of the different substituents on the thermodynamics of the condensation reactions of the synthesized compounds, we have conducted a series of calculations using density functional theory to compute the reaction energies. The calculations also investigated the effect of the substitutions on the hydrogen migration in the tautomerism effect and the energy splitting of the frontier orbitals.