t-BuOK-Mediated Transamidation System for Aromatic Amines and Multiple Acyl Donors

Abstract: A potassium tert-butoxide (t-BuOK)-mediated transamidation system for aromatic amines has been established in this study, enabling efficient transition-metal-free transamidation between aromatic amines/heterocyclic amines and multiple acyl donors. A total of 49 amide compounds were synthesized with yields ranging from 30% to 96%. Notably, the protocol features mild reaction conditions (≤50 °C, no microwave assistance) and achieves room-temperature trifluoroacetylation of heterocyclic amines, providing a green route for the synthesis of fluorine-containing pharmaceutical intermediates and complex heterocyclic amide skeletons. Mechanistic investigations, including radical scavenger experiments and 18-crown-6 chelation studies, reveal that the reaction proceeds via a K+ dual-coordination-driven nucleophilic addition-elimination pathway. Specifically, K+ acts as a hard Lewis acid to form an "aniline-K+-acyl donor" ternary complex, synergistically activating both the nucleophilic amine and electrophilic acyl donor, thereby facilitating amide C-N bond cleavage and target product formation.