Iron-catalyzed arene C–H cyanation suitable for complex molecules

Abstract

Direct functionalization of arene C(sp²)–H bonds to introduce a cyano group is synthetically valuable yet remains challenging, particularly in the absence of directing groups. Here we describe an iron system ligated with an amino acid that enables non-directed C–H cyanation of (hetero)arenes using trimethylsilyl cyanide as the cyanide source in the presence of persulfate. A simple Fe(OAc)₂/L-serine manifold provides efficient access to aryl nitriles with broad functional-group tolerance, compatibility with heteroarenes, and applicability to late-stage cyanation of bioactive molecules. Mechanistic studies support a radical pathway involving single-electron oxidation of the arene followed by cyanide trapping and oxidative rearomatization. This operationally simple protocol offers practical access to aryl nitriles and underscores the value of amino acid ligation in enabling iron-catalyzed oxidative C–H functionalization.