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

The complete chemoselective functionalization of aromatic C(sp(2))-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(sp(2))-H bond. The cycloheptatriene compound commonly observed through Buchner reaction or, when employing alkyl benzenes, the corresponding derivatives from C(sp(3))-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.
Support for this work was provided by the MINECO (Grants CTQ2014-62234-EXP, CTQ2014-52769-C3-R-1, CTQ2014-54306-P, CTQ2014-52525-P, and Grant BES-2012-052801 to V.P.), the Junta de Andalucia (Grant P10-FQM-06292) and the Generalitat de Catalunya (Grants 2017SGR39 and 2017SGR264, Xarxa de Referencia en Quimica Teorica i Computacional, ICREA Academia prizes 2013 to M.C. and 2014 to M.S.). The EU under the FEDER grant UNGI10-4E-801 (European Fund for Regional Development) has also funded this research.