Lewis Acid‐Promoted Regioselective Synthesis of N ‐Heteroarene Quaternary Salts of 10‐Chloro‐10‐Demethoxy Colchicine via Activation of α‐Halotropones

Herein, we report a Lewis acid‐mediated aromatic nucleophilic substitution (S N Ar) reaction of pre‐functionalized tropolone core of colchicine to furnish N ‐heteroarene quaternary salts. The synthesis of N ‐heteroarene quaternary salts of colchicine has been accomplished via C(sp 2 )─N(sp 2 ) bond formation, mediated by aluminum trifluoromethanesulfonate, through the reaction of 10‐chloro‐10‐demethoxy colchicine (10‐chloro‐colchicide) with various non‐nucleophilic N ‐heterocycles. The proposed methodology exhibits a broad substrate scope with good yield. This approach provides a valuable platform for future drug discovery efforts targeting bioactive natural products featuring the tropolone core.