Late-Stage Radical Ortho -C−H Sulfonylation of Peptides and Phenolic Drugs upon Iron Catalysis

The site-selective introduction of the sulfone scaffold in aromatic systems is a powerful synthetic tool within medicinal and organic chemistry. While significant attention has recently devoted to the sulfonylation of anilines, the parent process featuring phenols remains comparatively overlooked. Herein, a predictable iron-catalyzed radical sulfonylation of a broad spectrum of over 50 intricate phenols with versatile sulfonylmethyl isocyanides is described. This iron-based approach enables the predictable C−S radical coupling at the ortho C−H bond of biologically relevant phenols in a late-stage fashion. Mechanistic studies support the intermediacy of sulfonyl radical species.