Mechanism of the Selective Fe-Catalyzed Arene Carbon–Hydrogen Bond Functionalization

The complete chemoselective functionalization of aromatic C­(sp2)–H bonds of benzene and alkyl benzenes by carbene insertion from ethyl diazoacetate was unknown until the recent discovery of an iron-based catalytic system toward such transformation. A Fe­(II) complex bearing the pytacn ligand (pytacn = L1 = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane) transferred the CHCO2Et unit exclusively to the C­(sp2)–H bond. The cycloheptatriene compound commonly observed through Buchner reaction or, when employing alkyl benzenes, the corresponding derivatives from C­(sp3)–H functionalization are not formed. We herein present a combined experimental and computational mechanistic study to explain this exceptional selectivity. Our computational study reveals that the key step is the formation of an enol-like substrate, which is the precursor of the final insertion products. Experimental evidences based on substrate probes and isotopic labeling experiments in favor of this mechanistic interpretation are provided.