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Ikram Yagoub

Molecular catalysts and graphene-based materials for the development of sustainable bio-inspired multicatalytic 'one pot' processes

Published on 13 April 2022
Thesis presented April 13, 2022

Abstract:
N-alkylation of amines with alcohols is a method of choice for accessing compounds of pharmaceutical interest in a more sustainable way. This field of catalysis is now largely dominated by the use of molecular complexes in homogeneous phase. The proposed mechanism is based on hydrogen auto-transfer (HAT). Among the two main families of iron-based catalysts that have been developed, we have chosen to focus more particularly on iron(cyclopentadienone) type catalysts. These catalysts have several advantages: air stability and easy synthesis in few steps, as well as the possibility of modulating catalytic activity via ligand modification. Iron(cyclopentadienone) complexes have been shown to be effective catalysts but several challenges remain. The main problem in terms of substrates concerns the use of primary alcohols bearing electron-withdrawing groups but also secondary alcohols. In addition, they often require the use of high temperatures and/or unwanted additives. Reactions are most often carried out at solvent reflux or in closed vials for reaction times of up to days for some. This highlights the presence of a high-energy barrier within at least one stage of the catalytic cycle, severely limiting the application of these molecular catalysts to develop new reactivities. In addition, these molecular catalysts operate under homogeneous conditions making their recycling difficult and reducing the atom economy of the process as a whole. The development of efficient catalysts that can be recycled and can operate in milder conditions remains a challenge.
As a first step, an in-depth mechanistic study on the functioning of known molecular complexes of iron (cyclopentadienone)carbonyl is conducted. It has led to a better understanding of the chemical activation step of the catalyst by shedding light on the formation of new iron species.
In a second step, this same strategy was applied in the development of a new multi-catalytic process with the aim of synthesizing fluorinated pharmaceutical compounds. The results suggest that neither the mode of activation – i.e. chemical and/or thermal – nor the type of complex [LFe(CO)3] or [LFe(CO)2(NCPh)], has any influence on yields.
Finally, the grafting of these catalysts on a graphene surface was studied. Two types of grafting were considered: covalent grafting and supramolecular grafting. Our choice finally fell on supramolecular grafting. For this purpose, a synthetic pathway to access functionalized complexes with a perylene-type anchor has been developed. This strategy was established with the aim of developing a heterogeneous and therefore recyclable version of the catalyst.

Keywords:
One-pot, Iron complexes, N-alkylation of amines, Grafting