Electrochemical Chemo- and Regioselective Heterofunctionalization of Tropones via C(sp2)H Derivatization

A general electrochemical synthetic procedure for the site-selective heterofunctionalization of activated tropones is documented. Detailed voltametric analysis and quantum chemistry calculations enabled the development of a predictive model for the process efficiency, accounting for both reactivity and regioselectivity. Mono- and poly-halogenation, nitration, sulfonation, and thiocyanation protocols are successfully executed starting from inexpensive sodium salts under oxidative electrolytic conditions (35 examples, isolated yields up to 95%, faradaic efficiencies up to 95%). The implementation of an iterative electrochemical/metal-catalyzed cross-coupling synthetic strategy, along with the adaptation of the protocol for the preparation of biologically relevant tropolone derivatives, underscores the generality and robustness of the methodology