Polychlorinated Amides and Lactones via Electrochemically Mediated Copper-Catalyzed Atom Transfer Radical Addition

Electrochemically mediated atom transfer radical addition (<i>e</i>ATRA) catalyzed by copper(II) has recently emerged as a powerful and sustainable strategy for carbon-carbon (C-C) bond formation in organic synthesis. Utilizing robust organocopper(II) complexes, α-haloamides were explored herein, which revealed their efficient catalysis in <i>e</i>ATRA with a range of functionalized alkenes that afford unique polychlorinated amides. Interestingly, the initial <i>e</i>ATRA addition products undergo subsequent intramolecular cyclization to afford five-membered lactones, as controlled by the electron-withdrawing or electron-donating substitution pattern of the alkene. A key feature of this transformation is the electrochemical generation of an unusual and highly reactive O-bound copper(II) species, [Cu^II(Me₆tren)(OR)]⁺, in the presence of polyhalogenated primary amides. This O-bound amidate Cu complex gradually releases the amidyl radical (and [Cu^I(Me₆tren)]⁺) by Cu^II-O bond homolysis to promote efficient <i>e</i>ATRA. Mechanistic insights supported by cyclic voltammetry and ultraviolet-visible (UV-vis) spectroelectrochemical studies further clarify the role of copper intermediates in this process. This work demonstrates the versatility and efficiency of copper-catalyzed <i>e</i>ATRA under mild electrochemical conditions and from readily available starting materials.