Resumen de Towards more sustainable chemical processes: studies on covalent and non-covalent catalyst immobilization
Asymmetric catalysis has attracted plenty of interests to produce enantioenriched compounds. Therefore, development of effective, convenient and sustainable asymmetric catalysts and methodologies is of great demand. The present thesis describes different means to achieve these goals, including developing reusable catalysts, building up catalytic cascade reactions, synthesizing novel catalysts with improved activity, developing robust precatalyst and non-covalent immobilizing metallic catalysts.
Covalent supporting provides a convenient method to sustainable catalysts, which could be recycled and reused easily by filtration and also is applicable in continuous flow processes. In Chapter 2, we describe the development of a small family of polymer supported diphenylprolinol silyl ether catalysts for ¿-amination reactions, the catalyst loading can be lowered to 1-2 mol% (vs reported 10-20 mol% of homogeneous analogues) under optimal conditions. In addition, based on the study and understanding of the catalyst deactivation, a simple but effective solution for preventing catalyst deactivation has been developed, which allows catalyst recycling for up to ten consecutive times (TON = 480) and application of continuous flow process for ¿-amination reaction.
Benefit from the properties of polymers, immobilized catalysts onto them are naturally site-isolated. This could facilitate the incompatible catalysts (strong acid and bases) work in the same reaction media compatibly, which could be a general solution to build up ¿wolf-and-lamb¿ model cascade reactions. Chapter 3 has described two examples of cascade reactions involving acid-catalyzed decomposition of paraldehyde and amine-catalyzed asymmetric acetaldehyde addition reactions. It has been shown in the later case that the two PS-catalysts can be reused for more than seven cycles without separation from each other. Furthermore, the application of acetaldehyde cross-aldol reactions in medicinal drug synthesis has also been developed using simple reductive amination reactions.
In addition to reuse the catalyst, developing novel catalyst with high activity is also attractive. In Chapter 4, by exploiting catalytic desymmetrization strategy, a small family of 4-silyloxy-3-aminopyrrolidine catalysts has been synthesized, which has shown very high activity in anti-Mannich reactions. Improved activity was also observed in ¿-aminoxylation of aldehydes.
Chapter 5 focused the studies on Shibasaki¿s REMB frameworks. In order to address the drawback of water sensitive catalyst, by replacing the alkali metals with H-bonding donors, moisture-tolerated precatalysts could be achieved. The precatalsyts could be easily assembled into REMB catalysts in situ by mixing with alkali iodide salts, which acts the same catalytic activity in the test reactions. On the other hand, based on previous studies on ligand bindings with alkali metals, the effect of immobilized ligand to the catalytic activity of REMB was interesting because this would provide clues for the future target on non-covalent supporting of Shibasaki¿s bifunctional catalysts. Therefore, eight polymer-supported ligands have been synthesized and evaluated in the binding of RENaB catalyst. Solvent effect on the ¿catch and release¿ of catalyst has been observed. In addition, the catalytic activity is largely influenced by the ligand, linear amine ligand binded catalyst gave the highest enantioselectivity.
