The chemical industry is ever more focused on the development of sustainable and selective procedures for the synthesis of high-added value fine chemicals, in order to meet the demand in society for environment-friendly chemical processes. The metal-catalysed carbene and nitrene transfer reactions have proved to be an excellent strategy to achieve the goal, due to their ability to form C-C, C-N and C heteroatom bonds with high stereo- and regioselectivities. In addition, the good choice of the carbene and nitrene precursors can increase the reaction sustainability and the atom efficiency, as when diazo compounds and azides were used as starting materials thanks to the formation of molecular nitrogen as the only by product of the reaction. Among all the metal catalysed carbene and nitrene transfer reactions, the formation of three-membered ring compounds, such as cyclopropanes and aziridines, is a very attractive topic due to their use as building blocks in organic chemistry and their biological and/or pharmaceutical activity. Considering the catalytic activity of metal porphyrin complexes in promoting cyclopropanation and aziridination reactions of alkenes, the following PhD thesis aims to develop a new class of hybrid catalysts which are able to mediate carbene and nitrene transfer reactions under mild experimental conditions. In order to confer chiral recognition properties and modulate the catalyst properties, the conjugation of metal porphyrin complexes with bio scaffolds such as carbohydrates, amino acids, cellulose and β-lactoglobulins was studied. Carbohydrates are natural chiral, polyhydroxylated compounds which play critical roles in several biological processes, including the energy storage, cellular communications and recognitions, and the immune system maintenance. Glycoporphyrins, derived from the conjugation of porphyrin rings with sugar units, are efficient photosensitizers extensively used in photodynamic therapy (PDT) and they are desirable ligands for organometallic synthesis. To assess how different glycosylated porphyrin ligands can influence the catalytic activity of corresponding ruthenium and iron complexes, different meso glycosyl-conjugated porphyrins were synthesised. The number and position of carbohydrate units on the porphyrin skeleton play an important role in determining the ligand chemo-physical properties. Mono and tetra-glycosylated porphyrins were synthesized and the corresponding iron and ruthenium complexes were tested as catalysts of cyclopropanation and aziridination reactions. In the model cyclopropanation reaction between α-methylstyrene and EDA, Fe(III)(porphyrin)OMe complexes showed higher activity then Ru(II)(porphyrin)CO derivatives and obtained data indicated the strong dependence of the reaction diastereoselectivity on the ligand structure. Among all the iron complexes which were tested as cyclopropanation catalysts, Fe(15)OMe complex was chosen to study the reaction scope by testing different styrenes in view of the good compromise between the synthetic accessibility of synthesize it and reaction productivity (yields and diastereoselectivities). All the desired cyclopropanes were obtained in very good yields (up to 80%) and trans diastereoselectivities (up to 98:2). The obtained iron and ruthenium glycoporphyrin complexes were also tested in the model aziridination reaction between α-methylstyrene and 3,5-bis-(trifluoromethyl)phenylazide. Unfortunately, Fe(III)(porphyrin)OMe complexes didn’t catalyse the aziridination reaction but the desired product was obtained in a very good yield (83%) in the presence of Ru(15)CO. The latter catalyst was used to study the reactivity of α-methylstyrene towards different aryl azides and the obtained data indicated the ability of Ru(15)CO to promote the aziridination of azides showing different electronic and steric nature. Low yields were obtained in the presence of coordinating methoxy groups which can be responsible for the catalyst deactivation. Obtained results showed the applicability of Fe(15)OMe and Ru(15)CO as catalysts for the synthesis of three-membered ring compounds and the amphiphilic nature of ligand 15 can be suitable, after deprotection of the saccharide units, to perform catalytic reactions in biphasic systems. The second biomolecules class that has been studied in this thesis consists of aminoacidic residues. In order to synthesise new bio-inspired catalysts, the conjugation of α2β2 USCl porphyrin with the DAP aminoacid was studied. The desired product can be formed as a mixture of two different regioisomers. A similar ligand was obtained by reacting USCl porphyrin with the methyl ester of DAP aminoacid. The presence of different porphyrin derivatives was revealed by the 1H NMR analysis where several tetrapyrrolic NH signals, as well as different β pyrrole proton signals, were detected at very high fields indicating the presence of different conformations of the ligand skeleton. The 50B regioisomer of the desired bis-strapped porphyrin was isolated in 10% yield and characterized by NMR spectroscopy. The new ligand was used to synthesise the corresponding iron(III) complex, which was tested to promote the cyclopropanation reaction. In the optimised conditions, the Fe(50B)OMe complex was very active in promoting the reaction between α-methylstyrene and EDA, forming the desired cyclopropane in 99% yield and a trans/cis ratio of 90:10. Considering the very good result obtained in the model reaction, the catalytic performance of Fe(50B)OMe was tested in the presence of different substituted alkenes. Very good results were achieved in terms of yields (up to 99%) and disteroselectivities (up to 99:1). Under the optimized catalytic conditions, the desired cyclopropanes were formed in quantitative yields; lower yields were observed by using 0.001 mol % of Fe(50B)OMe due to the low conversion of the starting diazo compound. Obtained data showed the applicability of Fe(50B)OMe as an efficient catalyst for carbene transfer reactions. In addition, the presence of carboxylic groups on the porphyrin strap makes the synthesised hybrid ligand suitable for the conjugation with long water soluble chains, like PEG, in order to perform catalytic reaction in biphasic systems. Besides the conjugation of porphyrin ligands with small bio-scaffolds, like sugars and aminoacids, new mono-substituted porphyrins were designed and synthesized for their conjugation with cellulose and β-lactoglobuline proteins. In order to develop metal porphyrin complexes supported on cellulose, ligands 71 and 72, with amino groups onto the para position of one porphyrin ring phenyl group, were synthesized. Ligand 73 was synthesized with a long aliphatic chain that can be accommodated inside the tridimensional structure of β-lactoglobulin protein by hydrophobic interactions. Preliminary studies were performed for the conjugation of porphyrin 71 with a cellulose derivative functionalised with aldehyde groups. The conjugated material was obtained by a reductive amination reaction and then reacted with FeBr2 affording the corresponding iron(III) complex. Preliminary tests as cyclopropanation catalyst revealed the ability of the cellulose-based iron catalyst to promote the reaction between α-methylstyrene and EDA, forming the desired cyclopropane in 15% yield and a trans/cis ratio of 97:3. The promising result suggested the potential use as cyclopropanation catalyst of the conjugated heterogeneous species. Considering that metal porphyrin complexes show high activity in promoting carbene and nitrene transfer reactions, the obtained data represent a starting point to develop a new generation of catalysts which can be employed for the synthesis of several fine chemicals through sustainable synthetic methodologies. For developing sustainable and selective procedures for the synthesis of high-added value fine chemicals, a part of the PhD thesis was devoted to the study of the CO2 cycloaddition to three membered ring compounds in the presence of metal porphyrin complexes. Ruthenium bis-imido porphyrins were able to catalyse the regioselective cycloaddition of CO2 to aziridines to form oxoazolidinones, as reported in a previous PhD work. The catalytic performances of Ru(TPP)(NAr)2 (Ar = 3,5(CF3)2C6H3) (77) were also tested in the CO2 cycloaddition to epoxides. Very good results were obtained in the synthesis of different cyclic carbonates and the formation of the ruthenium species, Ru(TPP)(NAr)(ArNCOO-TBA+) (93), suggested the fundamental role of imido-axial ligand in activating CO2. The results, achieved in the CO2 cycloaddition of both epoxides and aziridines, suggested a mechanism in which the interaction of CO2 with the nitrogen imido atom is the first step of the reaction. This hypothesis is supported by the very high electron density on the nitrogen atom due to the linkage with ruthenium, as indicated by a previous DFT study. Future kinetics and DFT studies of the reaction between bis-imido complexes and CO2 could be useful to shed some light on the reaction mechanism. Considering the high activity of ruthenium porphyrin complexes to promote alkene aziridination reactions, the obtained data are the starting point to develop a catalytic system in which the same catalyst can be able to promote both the synthesis of aziridines and their transformation into oxazolidinones in a two-steps one-pot reaction which affords added value compounds in an efficient and sustainable way.
HYBRID CATALYSTS FOR CARBENE AND NITRENE TRANSFER REACTIONS / C. Damiano ; tutor: E. Gallo ; coordinatore: E. Licandro. - Milano : Università degli studi di Milano. DIPARTIMENTO DI CHIMICA, 2020 Jan 29. ((32. ciclo, Anno Accademico 2019.
|Titolo:||HYBRID CATALYSTS FOR CARBENE AND NITRENE TRANSFER REACTIONS|
|Supervisori e coordinatori interni:||LICANDRO, EMANUELA|
|Data di pubblicazione:||29-gen-2020|
|Parole Chiave:||carbene transfer; nitrene transfer; hybrid catalysts; porphyrins; bio-scaffolds; sugars; aminoacids; cellulose; proteins; cyclopropanes; aziridines; CO2; cyclic carbonates; oxoazolidinones|
|Settore Scientifico Disciplinare:||Settore CHIM/03 - Chimica Generale e Inorganica|
|Citazione:||HYBRID CATALYSTS FOR CARBENE AND NITRENE TRANSFER REACTIONS / C. Damiano ; tutor: E. Gallo ; coordinatore: E. Licandro. - Milano : Università degli studi di Milano. DIPARTIMENTO DI CHIMICA, 2020 Jan 29. ((32. ciclo, Anno Accademico 2019.|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.13130/damiano-caterina_phd2020-01-29|
|Appare nelle tipologie:||Tesi di dottorato|