C–H Bond Oxidation Catalyzed by an Imine-Based Iron Complex: A Mechanistic Insight

A family
of imine-based nonheme iron­(II) complexes (LX)2Fe­(OTf)2 has been prepared, characterized, and employed
as C–H oxidation catalysts. Ligands LX (X = 1, 2, 3, and 4) stand for tridentate imine ligands resulting from spontaneous
condensation of 2-pycolyl-amine and 4-substituted-2-picolyl aldehydes.
Fast and quantitative formation of the complex occurs just upon mixing
aldehyde, amine, and Fe­(OTf)2 in a 2:2:1 ratio in acetonitrile
solution. The solid-state structures of (L1)2Fe­(OTf)­(ClO4) and (L3)2Fe­(OTf)2 are reported, showing a low-spin octahedral iron center,
with the ligands arranged in a meridional fashion. 1H NMR
analyses indicate that the solid-state structure and spin state is
retained in solution. These analyses also show the presence of an
amine-imine tautomeric equilibrium. (LX)2Fe­(OTf)2 efficiently catalyze the oxidation of alkyl C–H bonds
employing H2O2 as a terminal oxidant. Manipulation
of the electronic properties of the imine ligand has only a minor
impact on efficiency and selectivity of the oxidative process. A mechanistic
study is presented, providing evidence that C–H oxidations
are metal-based. Reactions occur with stereoretention at the hydroxylated
carbon and selectively at tertiary over secondary C–H bonds.
Isotopic labeling analyses show that H2O2 is
the dominant origin of the oxygen atoms inserted in the oxygenated
product. Experimental evidence is provided that reactions involve
initial oxidation of the complexes to the ferric state, and it is
proposed that a ligand arm dissociates to enable hydrogen peroxide
binding and activation. Selectivity patterns and isotopic labeling
studies strongly suggest that activation of hydrogen peroxide occurs
by heterolytic O–O cleavage, without the assistance of a cis-binding water or alkyl carboxylic acid. The sum of these
observations provides sound evidence that controlled activation of
H2O2 at (LX)2Fe­(OTf)2 differs from that occurring in biomimetic iron catalysts
described to date.