Oxidation processes catalyzed by non-heme iron complexes using H2O2 as the terminal oxidant, represent one of the most promising green and sustainable approach to selectively functionalize non-activated C-H bonds. These biomimetic models of nonheme iron enzymes are activated by H2O2 to give an iron(III) hydroperoxide which is the precursor of the iron-oxo complex active species.
In this research field, in the first part of our project the nonheme imine-based iron complex easily prepared by self-assembly of 2 picolylaldehyde, 2 picolylamine, and Fe(OTf)2, an efficient catalyst for aliphatic C H bond oxidations, will be tested in the oxidation of aromatic compounds with H2O2. This process represents an important biochemical transformation which is also relevant from an industrial viewpoint. By using a series of alkylaromatic substrates, the chemoselectivity of aromatic vs side-chain oxidation will be analyzed. Oxidation of halogenated aromatics is also planned as a possible green strategy for the degradation of polluting haloaromatic compounds.
The oxidation mechanism will also be investigated by means of theoretical and experimental studies including the analysis of the electronic effects of substituents on the aryl mojety, kinetic isotope effect determinations, use of radical scavengers, inter- and intramolecular substituent effects in rearrangement experiments.
The second part of the project will be dedicated to the analysis of the catalytic activity of a highly selective supramolecular catalyst obtained by assembling a bipyrrolidine iron complex with two crown ether recognition sites. This artificial nonheme iron enzyme will be tested as a catalyst in the oxidation with H2O2 of suitable substrates such as hydrocarbons functionalized with ammonium groups that could bound the crown ether with high affinity by means of hydrogen bonding. In fact, once complexed to the crown-ether recognition sites, these substrates could be selectively oxidized at a specific site.
The most widely used approach to obtain high level of selectivity in C-H oxidation promoted by nonheme iron complexes has been based so far on the synthesis of bulky and sterically congested ligands where the hydrogen atom transfer to the metal-oxo active species may occur exclusively from C-H bonds correctly oriented with respect to the metal center. These catalysts however are characterized by complex, elaborated and expensive synthetic procedures, that hamper their application.
For the oxidation of aromatic compounds the use of the nonheme imine-based iron catalyst 1 may represents a significant innovation with great advantages with respect to other catalytic systems. Preliminary results obtained in the oxidation of benzylic alcohols do indicate that this catalytic system is rather selective towards the oxidation of the aromatic nucleus in the presence of alternative and competitive oxidations involving for example the alkylaromatic side-chain.
In this respect the selective oxidation of the aromatic ring might be exploited for the synthesis of the amino acid tyrosine by oxidation of phenylalanine.
The lack of free coordination sites in the imine-iron catalyst offers another advantage. A lower level of deactivation and a higher catalytic turnover number should be expected in view of the lack of product (phenol) binding. This aspect is particularly relevant in the oxidation of halogenated and polluting aromatic hydrocarbons, a strategic process in the field of green chemistry.
Concerning the second part of the project, the development of biomimetic supramolecular catalysts, which can represent good models of artificial enzymes, would provide a highly innovative approach to the accomplishment of highly regio- and stereoselective oxidative transformations useful from a synthetic and industrial point of view. In this context our supramolecular catalyst 2 might represent an efficient biomimetic systems possessing a highly performing catalytic site (bipyrrolidine-iron catalytic core) linked to a specific recognition site (two crown ethers).
The molecular recognition of different substrates with the binding sites directly linked to the nonheme iron complex allows the control of the specific position to be functionalized in the oxidative processes.