An Electrochemical Amidation/C-H Halogenation Cascade for the Sustainable Synthesis of Halogenated N-Aryl Amides, Carbamates and Ureas

Considering the significant future benefits of widespread sustainable chemical practices, the development of green synthetic methodologies remains a critical objective in modern chemistry. Amide groups and halogen atoms are ubiquitous in chemical and biological systems, with their structural and pharmacological significance enabling multiple applications in the fields of organic and medicinal chemistry. As a result, there is currently a major demand for methods that allow for the efficient construction of amide bonds and selective halogenation under environmentally friendly conditions. Existing approaches typically require distinct methods for amide bond formation and halogenation, often relying on activating reagents or catalysts, complex reaction conditions, and additives, which can hinder scalability and accessibility. With the aim of addressing these shortcomings of existing strategies, we report an electrochemical cascade methodology that enables the atom-economical and environmentally benign synthesis of halogenated N-aryl amide, carbamate and urea derivatives, which proceeds via amide bond formation followed by electrocatalytic C-H chlorination. The robustness of this method is demonstrated through the synthesis of over 180 such products, encompassing a wide range of functional groups and complex molecular scaffolds, and including many pharmaceutically relevant compounds and several scale-up examples.