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Application of amines for the preparation of chiral cyclic compounds
Formánek, Bedřich ; Veselý, Jan (advisor) ; Kočovský, Pavel (referee) ; Soural, Miroslav (referee)
Organocatalysis, along with catalysis by metal complexes or enzymes, has become one of the very useful tools of asymmetric synthesis. Different activation modes or their combinations into sequences (domino reactions) enable effective access to enantiomerically enriched complex substances. The objective of this work was the preparation of chiral molecules from simple precursors activated by amine-based organocatalysts. In particular, we were focused on a study of asymmetric allyl substitution of Morita-Baylis-Hillman carbonates and two-component domino reactions on sulfur-containing heterocycles. The thesis deals with the organocatalytic allyl amination of Morita-Baylis-Hillman carbonates with aromatic amines catalyzed by β-isocupreidine. The corresponding allylic amines were obtained in high yields (90-96%) with moderate enantiomeric excess. It was possible to get substances of high optical purity (ee 82-99%) by recrystallization of selected products. Furthermore, the developed method was applied in the preparation of enantiomerically enriched β-lactams, which represent valuable precursors, for example, in the synthesis of the drug Ezetimibe. The second part of the work is focused on stereoselective cyclization reactions comprising selected sulfur heterocycles. Although the cyclization reaction of...
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Preparation of enantiomerically pure cyclic compounds via organocatalytic concept
Remeš, Marek
Since 2000 the organocatalytic synthesis has developed massively in a third pillar of asymmetric synthesis standing next to catalysis with metal complexes and enzymatic catalysis. Organocatalysts, due to their various activation modes which could be combined in domino reactions, offer a way for a synthesis of complex molecules from a simple starting material. This thesis deals with investigation of usage of chiral secondary amines as catalysts for asymmetric synthesis of cyclic compounds. The main part of research was devoted to development of organocatalytic method leading to synthesis of enantiomerically pure cyclopentanecarbaldehydes and nitrocyclopentanecarbaldehydes. We focused also on the organocatalytic preparation of cyclohexanecarbaldehydes. During this work we developed an asymmetric domino Michael addition/α- substitution reaction of 2-(2-bromoethyl)malonates resp. 1-bromo-3-nitropropane with various enals catalyzed by chiral secondary amine. In the first case cyclopentanecarbaldehydes were formed where two chiral centres were created. In second case nitrocyclopentanecarbaldehydes were formed where three chiral centres were created. Yields of such developed reaction protocol reach up to 74 % and the reaction proceeds with excellent diastereo- and enantioselectivity (up to 19:1 d.r. and...
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Preparation of enantiomerically pure cyclic compounds via organocatalytic concept
Remeš, Marek
Since 2000 the organocatalytic synthesis has developed massively in a third pillar of asymmetric synthesis standing next to catalysis with metal complexes and enzymatic catalysis. Organocatalysts, due to their various activation modes which could be combined in domino reactions, offer a way for a synthesis of complex molecules from a simple starting material. This thesis deals with investigation of usage of chiral secondary amines as catalysts for asymmetric synthesis of cyclic compounds. The main part of research was devoted to development of organocatalytic method leading to synthesis of enantiomerically pure cyclopentanecarbaldehydes and nitrocyclopentanecarbaldehydes. We focused also on the organocatalytic preparation of cyclohexanecarbaldehydes. During this work we developed an asymmetric domino Michael addition/α- substitution reaction of 2-(2-bromoethyl)malonates resp. 1-bromo-3-nitropropane with various enals catalyzed by chiral secondary amine. In the first case cyclopentanecarbaldehydes were formed where two chiral centres were created. In second case nitrocyclopentanecarbaldehydes were formed where three chiral centres were created. Yields of such developed reaction protocol reach up to 74 % and the reaction proceeds with excellent diastereo- and enantioselectivity (up to 19:1 d.r. and...
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Preparation of enantiomerically pure cyclic compounds via organocatalytic concept
Remeš, Marek ; Veselý, Jan (advisor) ; Potáček, Milan (referee) ; Cibulka, Radek (referee)
Since 2000 the organocatalytic synthesis has developed massively in a third pillar of asymmetric synthesis standing next to catalysis with metal complexes and enzymatic catalysis. Organocatalysts, due to their various activation modes which could be combined in domino reactions, offer a way for a synthesis of complex molecules from a simple starting material. This thesis deals with investigation of usage of chiral secondary amines as catalysts for asymmetric synthesis of cyclic compounds. The main part of research was devoted to development of organocatalytic method leading to synthesis of enantiomerically pure cyclopentanecarbaldehydes and nitrocyclopentanecarbaldehydes. We focused also on the organocatalytic preparation of cyclohexanecarbaldehydes. During this work we developed an asymmetric domino Michael addition/α- substitution reaction of 2-(2-bromoethyl)malonates resp. 1-bromo-3-nitropropane with various enals catalyzed by chiral secondary amine. In the first case cyclopentanecarbaldehydes were formed where two chiral centres were created. In second case nitrocyclopentanecarbaldehydes were formed where three chiral centres were created. Yields of such developed reaction protocol reach up to 74 % and the reaction proceeds with excellent diastereo- and enantioselectivity (up to 19:1 d.r. and...
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