Homogeneous catalysis is a constantly growing and evolving area of study: in the last forty years many discoveries have been reported in both industrial and academic fields. Thanks to the use of organometallic catalysts, many inorganic and organic reactions of great importance have been revolutionized, so that homogeneous catalysis is now essential in many aspects of organic chemistry and for several industrial processes. On the other hand, heterogeneous catalysis is important because of its easier application in industry. Heterogeneous single site catalysts in many cases show superior performances in terms of activity, selectivity and recyclability coupling together the advantages of heterogeneous and homogeneous systems. It is important to note that the most commonly used ligands to form catalytic complexes often need really complicated synthesis so that the cost of the catalyst becomes excessive. In our research group we are focusing on the synthesis of molecules obtainable in few synthetic steps and easy to modify in order to be used as asymmetric ligands for transition metals. In particular we have prepared and fully characterised a small library of non-chiral and chiral pyridine containing macrocyclic ligands (Pc-L) possessing the same donor properties but with either C1, C2 or C2v symmetry. The strategy adopted for the synthesis of these macrocyclic ligands is very flexible and allows for structural modifications. Relative basicity of the four nitrogens atoms and metal complexation of Pc-L ligands with different copper(I) salts were studied. The use of [Cu(I)(Pc-L)] complexes was investigated at first in Henry catalytic reaction under mild conditions. The remarkable diastereoselectivity observed when isatine was reacted with nitroethane under the optimised catalytic conditions is worth to note, considering the easy access to a highly functionalized isatine skeleton. However, further studies on the ligand steric requirements in order to achieve significant enantioselectivities are required. Then [Cu(I)(Pc-L)] complexes were tested as competent catalysts in asymmetric cyclopropanation reactions, at first under homogenous conditions in 1,2-dichloroethane. Cyclopropanes were obtained in good to excellent yields and enantiomeric excesses up to 99%. Thanks to the collaboration with Dr. Dal Santo, we have developed supported hydrogen-bonded (SHB) chiral copper(I) complexes. These supported catalysts showed good performances in cyclopropanation reactions under heterogeneous conditions in batch. The heterogeneised systems showed higher or comparable activities than the homogeneous counterpart and a good recyclability, allowing the use of more environmentally friendly n-hexane as solvent in place of 1,2-dichloroethane. Cyclopropanes were obtained in good to excellent yields and enantiomeric excesses up to 67%. We did not observe any significant Cu leaching when employing n-hexane as a reaction medium and the catalytic system is of truly heterogeneous nature, since the filtered solution is not catalytically active. The observed confinement effects are more dependent on the employed solvent (non-polar vs halogenated) than to the kind of support (ordered or non-ordered). Worth to note is the fact that even commercial silica can be used as a support, without any need of structural modification of the ligand in order to strongly graft the complex. Thanks to the three month collaboration with Prof. David J. Cole-Hamilton from the University of St. Andrews (UK), these catalytic system based on SHB chiral copper(I) complexes were also tested as competent catalysts for asymmetric cyclopropanation reactions under flow conditions allowing the use of more eco-sustainable CO2 as a vector instead of solvents normally used for these reactions. The heterogeneised systems under flowing CO2 showed comparable or even higher chemoselectivities than the homogeneous counterpart. In terms of enantioselection excellent results were obtained also with non-activated alkenes like 1-octene where ees are comparable to those observed in the homogenous phase. Interestingly, all the data in CO2 were obtained at 40°C, while the best temperature for the cyclopropanation reaction in the homogenous phase was 0°C. Moreover supported catalysts showed a good recyclability and the TON number has been increased (up to 440). The catalysts system remained active up to 25 h without any loss in catalytic activity and chemoselectivity improved upon prolonged reaction times. Catalyst were stable and robust with a negligible copper leaching (0.007% of total copper). Future studies will be devoted to optimise the ligand design in order to improve the stereo-selective outcome of the reaction. Collaborating with Dr. Giorgio Abbiati, we next extend our studied on metal complexes testing our ligands with other metal ions in order to explore the coinage group. We have prepared silver(I) complexes of Pc-L* with different silver(I) salts. The [Ag(I)(Pc-L)] complexes demonstrated to be suitable catalysts for the synthesis of 1-alkoxyisocromenes starting from various 2-alkynylbenzaldehydes and different primary and secondary alcohols. Best results were obtained with BF4-complex. The approach is characterised by absolute regioselectivity, mild reaction condition, good to excellent reaction yields, cleanness of the reaction, reduced purification steps. The [Ag(I)(Pc-L)] complexes are quite stable, versatile and can be used under open-air atmosphere. The reaction mechanism was investigated by in depth NMR studies and an aimed intramolecular trapping experiment. Our efforts are now devoted to the development of an enantioselective version of this transformation. Finally the synthesis of several tiosemicarbazide derived Schiff base copper complexes has been reported. They have been fully characterised with spectral and analytical experiments. All synthesised complexes showed excellent catalytic activities in cyclopropanation reactions and TON up to 18,400 could be obtained. In contrast to the prolonged EDA addition time generally required to reduce the formation of homo-coupling products in cyclopropanation, we found those complexes very selective. Furthermore, a single addition of EDA is required to yield the desired cyclopropanes in excellent yields. Moreover, the catalysts are very robust and no decrease in yield was observed even after three catalytic runs. Several cyclopropanes have been obtained in good to excellent yields even from non-activated olefins. In the case of the cyclopropanation of (-)b-pinene, out of four possible diastereoisomers, only one product was formed that could be isolated pure in 84% yield.

SYNTHESIS, CHARACTERIZATION AND CATALYTIC ACTIVITY OF CHIRAL TETRAAZAMACROCYCLE - PC-L* -CU(I) AND AG (I) COMPLEXES / B. Castano ; tutor: A. Caselli ; co-tutor: E. Gallo ; co-ordinator: E. Licandro. Università degli Studi di Milano, 2014 Jan 16. 26. ciclo, Anno Accademico 2013. [10.13130/castano-brunilde_phd2014-01-16].

SYNTHESIS, CHARACTERIZATION AND CATALYTIC ACTIVITY OF CHIRAL TETRAAZAMACROCYCLE - PC-L* -CU(I) AND AG (I) COMPLEXES

B. Castano
2014

Abstract

Homogeneous catalysis is a constantly growing and evolving area of study: in the last forty years many discoveries have been reported in both industrial and academic fields. Thanks to the use of organometallic catalysts, many inorganic and organic reactions of great importance have been revolutionized, so that homogeneous catalysis is now essential in many aspects of organic chemistry and for several industrial processes. On the other hand, heterogeneous catalysis is important because of its easier application in industry. Heterogeneous single site catalysts in many cases show superior performances in terms of activity, selectivity and recyclability coupling together the advantages of heterogeneous and homogeneous systems. It is important to note that the most commonly used ligands to form catalytic complexes often need really complicated synthesis so that the cost of the catalyst becomes excessive. In our research group we are focusing on the synthesis of molecules obtainable in few synthetic steps and easy to modify in order to be used as asymmetric ligands for transition metals. In particular we have prepared and fully characterised a small library of non-chiral and chiral pyridine containing macrocyclic ligands (Pc-L) possessing the same donor properties but with either C1, C2 or C2v symmetry. The strategy adopted for the synthesis of these macrocyclic ligands is very flexible and allows for structural modifications. Relative basicity of the four nitrogens atoms and metal complexation of Pc-L ligands with different copper(I) salts were studied. The use of [Cu(I)(Pc-L)] complexes was investigated at first in Henry catalytic reaction under mild conditions. The remarkable diastereoselectivity observed when isatine was reacted with nitroethane under the optimised catalytic conditions is worth to note, considering the easy access to a highly functionalized isatine skeleton. However, further studies on the ligand steric requirements in order to achieve significant enantioselectivities are required. Then [Cu(I)(Pc-L)] complexes were tested as competent catalysts in asymmetric cyclopropanation reactions, at first under homogenous conditions in 1,2-dichloroethane. Cyclopropanes were obtained in good to excellent yields and enantiomeric excesses up to 99%. Thanks to the collaboration with Dr. Dal Santo, we have developed supported hydrogen-bonded (SHB) chiral copper(I) complexes. These supported catalysts showed good performances in cyclopropanation reactions under heterogeneous conditions in batch. The heterogeneised systems showed higher or comparable activities than the homogeneous counterpart and a good recyclability, allowing the use of more environmentally friendly n-hexane as solvent in place of 1,2-dichloroethane. Cyclopropanes were obtained in good to excellent yields and enantiomeric excesses up to 67%. We did not observe any significant Cu leaching when employing n-hexane as a reaction medium and the catalytic system is of truly heterogeneous nature, since the filtered solution is not catalytically active. The observed confinement effects are more dependent on the employed solvent (non-polar vs halogenated) than to the kind of support (ordered or non-ordered). Worth to note is the fact that even commercial silica can be used as a support, without any need of structural modification of the ligand in order to strongly graft the complex. Thanks to the three month collaboration with Prof. David J. Cole-Hamilton from the University of St. Andrews (UK), these catalytic system based on SHB chiral copper(I) complexes were also tested as competent catalysts for asymmetric cyclopropanation reactions under flow conditions allowing the use of more eco-sustainable CO2 as a vector instead of solvents normally used for these reactions. The heterogeneised systems under flowing CO2 showed comparable or even higher chemoselectivities than the homogeneous counterpart. In terms of enantioselection excellent results were obtained also with non-activated alkenes like 1-octene where ees are comparable to those observed in the homogenous phase. Interestingly, all the data in CO2 were obtained at 40°C, while the best temperature for the cyclopropanation reaction in the homogenous phase was 0°C. Moreover supported catalysts showed a good recyclability and the TON number has been increased (up to 440). The catalysts system remained active up to 25 h without any loss in catalytic activity and chemoselectivity improved upon prolonged reaction times. Catalyst were stable and robust with a negligible copper leaching (0.007% of total copper). Future studies will be devoted to optimise the ligand design in order to improve the stereo-selective outcome of the reaction. Collaborating with Dr. Giorgio Abbiati, we next extend our studied on metal complexes testing our ligands with other metal ions in order to explore the coinage group. We have prepared silver(I) complexes of Pc-L* with different silver(I) salts. The [Ag(I)(Pc-L)] complexes demonstrated to be suitable catalysts for the synthesis of 1-alkoxyisocromenes starting from various 2-alkynylbenzaldehydes and different primary and secondary alcohols. Best results were obtained with BF4-complex. The approach is characterised by absolute regioselectivity, mild reaction condition, good to excellent reaction yields, cleanness of the reaction, reduced purification steps. The [Ag(I)(Pc-L)] complexes are quite stable, versatile and can be used under open-air atmosphere. The reaction mechanism was investigated by in depth NMR studies and an aimed intramolecular trapping experiment. Our efforts are now devoted to the development of an enantioselective version of this transformation. Finally the synthesis of several tiosemicarbazide derived Schiff base copper complexes has been reported. They have been fully characterised with spectral and analytical experiments. All synthesised complexes showed excellent catalytic activities in cyclopropanation reactions and TON up to 18,400 could be obtained. In contrast to the prolonged EDA addition time generally required to reduce the formation of homo-coupling products in cyclopropanation, we found those complexes very selective. Furthermore, a single addition of EDA is required to yield the desired cyclopropanes in excellent yields. Moreover, the catalysts are very robust and no decrease in yield was observed even after three catalytic runs. Several cyclopropanes have been obtained in good to excellent yields even from non-activated olefins. In the case of the cyclopropanation of (-)b-pinene, out of four possible diastereoisomers, only one product was formed that could be isolated pure in 84% yield.
16-gen-2014
Settore CHIM/03 - Chimica Generale e Inorganica
tetraazamacrocyclic ligands ; homogeneous catalysis ; heterogeneous catalysis ; cyclopropanation reactions ; Henry reaction ; copper(I) complexes ; assymetric catalysis ; silver(I) complexes ; supported catalysts
CASELLI, ALESSANDRO
LICANDRO, EMANUELA
Doctoral Thesis
SYNTHESIS, CHARACTERIZATION AND CATALYTIC ACTIVITY OF CHIRAL TETRAAZAMACROCYCLE - PC-L* -CU(I) AND AG (I) COMPLEXES / B. Castano ; tutor: A. Caselli ; co-tutor: E. Gallo ; co-ordinator: E. Licandro. Università degli Studi di Milano, 2014 Jan 16. 26. ciclo, Anno Accademico 2013. [10.13130/castano-brunilde_phd2014-01-16].
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