Site-selective C-H functionalization of aliphatic alkyl chains is a longstanding challenge in oxidation catalysis, given the comparable relative reactivity of the different methylenes. A supramolecular, bioinspired approach is described to address this challenge. A Mn complex able to catalyze C(sp )-H hydroxylation with H O is equipped with 18-benzocrown-6 ether receptors that bind ammonium substrates via hydrogen bonding. Reversible pre-association of protonated primary aliphatic amines with the crown ether selectively exposes remote positions (C8 and C9) to the oxidizing unit, resulting in a site-selective oxidation. Remarkably, such control of selectivity retains its efficiency for a whole series of linear amines, overriding the intrinsic reactivity of C-H bonds, no matter the chain length.

An iminopyridine FeIJII) complex, easily prepared in situ by self-assembly of cheap and commercially available\ud starting materials (2-picolylaldehyde, 2-picolylamine, and FeIJOTf)2 in a 2 : 2 : 1 ratio), is shown to be an\ud effective catalyst for the direct hydroxylation of aromatic rings with H2O2 under mild conditions. This catalyst\ud shows a marked preference for aromatic ring hydroxylation over lateral chain oxidation, both in intramolecular\ud and intermolecular competitions, as long as the arene is not too electron poor. The selectivity\ud pattern of the reaction closely matches that of electrophilic aromatic substitutions, with phenol yields and\ud positions dictated by the nature of the ring substituent (electron-donating or electron-withdrawing, orthopara\ud or meta-orienting). The oxidation mechanism has been investigated in detail, and the sum of the accumulated\ud pieces of evidence, ranging from KIE to the use of radical scavengers, from substituent effects\ud on intermolecular and intramolecular selectivity to rearrangement experiments, points to the predominance\ud of a metal-based SEAr pathway, without a significant involvement of free diffusing radical pathways

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. (1)H 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.