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.