Iron(III)-Mediated C–H Alkylation: One-Electron Differentiation Increases Activity and Chemoselectivity

The C–H functionalization of arenes mediated by well-defined bis(phosphine)-supported organometallic iron(III) complexes is described. One-electron oxidation of trans-(depe)₂Fe(CH₃)₂ (depe = 1,2-bis(diethylphosphino)ethane) generated the corresponding isolable iron(III) dimethyl derivative that was unstable toward Fe–CH₃ homolysis. Oxidation of the corresponding iron(II) bis(aryl) complex trans-(depe)₂Fe(tolyl)₂ resulted in rapid reductive elimination of the biaryl with formation of iron(I). These observations motivated the synthesis of the cationic iron(III) metallacycle derived from C–H activation of a neophyl ligand. This complex mediated the ortho-selective C(sp²)–H alkylation of a host of arene derivatives containing ketone, amide, pyridine, ester, and sulfoxide directing groups with greater selectivity and reactivity than the iron(II) counterpart. The effect of bis(phosphine) ligands was examined, where decreasing ligand lability correlated with a higher barrier. The experimental rate law, deuterium labeling studies, deuterium kinetic isotope effect experiments, and computational modeling support a reversible C–H activation step followed by rate-determining C(sp²)–C(sp³) reductive elimination. Using design principles to minimize undesired reactivity, the iron(III) cycloneophyl complex mediated more facile and chemoselective C–H functionalization with a broader directing group compatibility than the iron(II) analog, arising from a combination of increased ligand lability, less exergonic substrate coordination, an enhanced orbital hybridization effect in C–H activation, and more facile C–C reductive elimination.