Iron-Catalyzed Selective C(sp²)-C(sp³) Coupling of Nitro(hetero)arenes and Alkyl Bromides by Paired Electrolysis

Developing simple and sustainable strategies for the efficient functionalization of nitro(hetero)arenes at specific sites is essential for minimizing experimental procedures and waste emissions and for advancing the green synthesis of antitumor active molecules. In this study, we present a linear paired electrolysis strategy that enables iron-catalyzed C(sp²)-C(sp³) coupling of nitro(hetero)arenes with alkyl bromides in a one-pot process, thereby generating a variety of para-alkylated nitro(hetero)arene derivatives. The control experiments and CV experiments have successfully demonstrated that our protocol proceeds via a sequential process of SER/radical addition/SEO. The process highlights two crucial aspects: nitro(hetero)arenes act as mediators to promote the generation of alkyl radicals; the iron catalyst significantly lowers the activation energy and ensures high para-selectivity in the radical addition. These key mechanisms have been theoretically validated through DFT calculations. Notably, the protocol is distinguished by broad functional group compatibility, scalability, high energy efficiency, and mild conditions, demonstrating practicality in the late-stage modification of biorelevant compounds and the synthesis of pharmaceutical intermediates, including IDO inhibitors, which represent a clinically relevant class of small molecules in cancer immunotherapy.