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

Abstract

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 CHCO 2 Et 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 labelling experiments in favor of this mechanistic interpretation are provided. KEYWORDS carbene transfer iron catalysis C-H activation C(sp 2)-H functionalization DFT calculations

Electrophilic Iron Catalyst Paired with a Lithium Cation Enables Selective Functionalization of Non‐Activated Aliphatic C−H Bonds via Metallocarbene Intermediates

“…This scenario is reminiscent to the one recently reported for the C(sp 2 )−H bond alkylation reactions via non‐heme iron‐carbene species. In this case, computational studies rationalize the high reaction temperatures (80 °C) required for dissociation of an unproductive Fe–O(C) adduct formed between the iron catalyst and the oxygen atom of the carbonyl group of ethyl diazoacetate …”

Iron catalysts with N-ligands for carbene transfer of diazo reagents

“…A deeper investigation of the alkylation of non-activated aromatic C(sp 2 )-H bonds was undertaken by using both experimental and theoretical approaches. 192 The catalytic procedure reported above 191 for the functionalization of aromatic C-H bonds required two equivalents of NaBAr F , with respect to complex 237, to allow the reaction to proceed. This indicated that two available coordination sites on the metal center are necessary for accomplishing the carbene insertion.…”

C-H Functionalization via Iron-Catalyzed Carbene-Transfer Reactions

“…In this context, Luis, Perez, and coworkers reported on the use of iron(II)-complex (23) bearing a pytacn ligand in the reaction of ethyl diazoacetate 2 with aromatic hydrocarbons (21). Under these reaction conditions, ethyl diazoacetate (2) underwent a chemoselective C-H functionalization of the aromatic C(sp 2 )-H bond of benzene and alkyl benzene derivatives, and only trace amounts of the norcaradiene/cycloheptatriene reaction pathway were observed [31]. The substrate scope of benzene derivatives was further studied by the same authors and, in all cases, exclusive C(sp 2 )-H bond insertion occurred in moderate to good yields as a mixture of regioisomers.…”