|
|
The preparation of chiral NHC carbene precatalysts
Krejčířová, Kateřina ; Veselý, Jan (advisor) ; Míšek, Jiří (referee)
This bachelor thesis is focused on the preparation of chiral NHC carbene precatalysts, which are used as organocatalysts in a variety of organic transformations leading to the formation of optically active compounds. In the course of this work, several triazolium salts were prepared from suitable starting materials using six reaction steps. Triazolium salts derived from oxazolidinone were obtained from well available starting materials, arylhydrazines and phenylalanine.
|
|
|
Enantioselective Synthesis of Chiral Cyclohexenones Using NHC Catalysis
Lóška, Ladislav ; Veselý, Jan (advisor) ; Rýček, Lukáš (referee)
This work deals with the enantioselective synthesis of chiral cyclohexenones from substituted 4-nitroisoxazoles and α-bromo-α,β-unsaturated aldehydes using of N-heterocyclic carbenes (NHC) as organocatalysts. The work includes the preparation of commercially unavailable NHC-precursors and the synthesis of starting materials, substituted 4-nitroisoxazoles and α-bromo-α,β-unsaturated aldehydes. The second part of the work deals with the optimization of reaction conditions of the enantioselective synthesis of chiral cyclohexenones, proceeding via an azolium dienolate intermediate, and the detailed substrate scope screening.
|
|
|
Synthesis of 4-alkylidenepyrazolones and their use in preparation of spirocycles
Boudová, Hana ; Veselý, Jan (advisor) ; Matoušová, Eliška (referee)
Due to the wide use of spirocyclic compounds containing heterocycles, especially in medicinal chemistry, this bachelor thesis deals with the preparation of 4-alkylidenepyrazolones and their use to prepare pyrazolone-derived spirocyclic compounds using organocatalysis with tertiary amines. 4-Alkylidenepyrazolones were prepared by Knoevenagel condensation of pyrazolones and aldehydes, the preparation of spiropyrazolones was carried out by the cyclization reaction of 3-nitropropyl-mesylate with suitable 4-alkylidenepyrazolone derivatives. Key words 4-alkylidenpyrazolones, α,β-unsaturated pyrazolones, Knoevenagel reaction, 3-nitropropyl-mesylate, spirocyclic compounds, spiropyrazolones, organocatalysis
|
|
|
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...
|
|
|
Synthesis of cyclodextrin derivatives for organocatalysis
Chena Tichá, Iveta
Synthesis of cyclodextrin derivatives for organocatalysis This doctoral thesis examines the preparation of new cyclodextrin (CD) derivatives suitable for organocatalysis. The aim of this work is to prepare monosubstituted and disubstituted CD derivatives as organocatalysts for different types of enantioselective reactions potentially performed in water. In addition, disubstituted CD derivatives require considering the potential mixture of regioisomers and pseudoenantiomers. Thus, this thesis is divided into several sections - preparation of CD precursors and derivatives for organocatalysis, preparation of pure regioisomers and pseudoenantiomers of disubstituted CDs and final application of CD derivatives in enantioselective reactions. Furthermore, this thesis also focuses on the molecular modeling of the prepared CD derivatives and on their catalytic activity in silico. The first section covers the preparation of new disubstituted CD precursors as pure regioisomers for organocatalysts, specifically to develop a new method for the preparation of heterodisubstituted AC regioisomers on the primary rim of α-CD. This section also includes the determination of the regioisomer ratios of common α-CD intermediates disubstituted on the primary rim to evaluate their potential as precursors in organocatalysis....
|
|
|
Synthesis of New Types of Biologically Active Substances Using the Organometallic Compounds
Korotvička, Aleš
This work consists of four separate chapters. Although they are seemingly different projects, they have a common feature - the application of organometallic chemistry. 1. Lusianthridin and denbinobin, the phenanthrene derivatives, can be found in plants of the family Orchidaceae. They exhibit cytostatic activity against cancer of human lung and ovarian and against promyelocytic leukemia. Therefore, new synthetic methods for these substances may be applied in research and development of new bioactive compounds. I prepared 9,10- disubstituted phenanthrenes through reactions of biphenylene with alkynes, which were catalyzed by iridium complexes. Phenanthridine derivatives are found naturally in the group benzo[c]phenanthridine alkaloids. The most famous of these include sanguinarine and chelerythrine. Sanguinarine selectively induces apoptosis (planned cell death) of human cancer cells and, therefore, is investigated as a potential antitumor agent. Chelerythrine selectively inhibits protein kinase C, leading again to apoptosis. I have studied reactions of biphenylene with nitriles catalyzed by rhodium complexes that have not been described yet. By this, I prepared a series of 6-substituted phenanthridines. 2. Carboranes are artificially prepared organic compounds of boron, which are not represented in...
|
|
|
Synthesis of the C15-C20 tiacumicin fragment
Havlíček, Vojtěch
In the diploma thesis, a method for preparation of the unsaturated C15-C20 tiacumicin fragment was developed. Tiacumicin is classified as a macrolidone antibiotic. Although three syntheses of tiacumicin have been recently published, this study has aimed to develop a novel pathway for its preparation utilizing catalytic reactions instead of stoichiometric ones. In the second part, an enantioselective allylation of (E)-3-jod-2-methylpropenal has been developed applying catalysis by a series of N,N'-dioxide catalysts. The asymmetric induction achieved in the allylation was up to 99% ee. This procedure allows relatively simple, straightforward and efficient preparation of wide range of natural products. Keywords tiacumicin, asymmetric synthesis, allylation, catalysis, chiral Lewis bases, organocatalysis
|
|
|
Synthesis of the C15-C20 tiacumicin fragment
Havlíček, Vojtěch
In the diploma thesis, a method for preparation of the unsaturated C15-C20 tiacumicin fragment was developed. Tiacumicin is classified as a macrolidone antibiotic. Although three syntheses of tiacumicin have been recently published, this study has aimed to develop a novel pathway for its preparation utilizing catalytic reactions instead of stoichiometric ones. In the second part, an enantioselective allylation of (E)-3-jod-2-methylpropenal has been developed applying catalysis by a series of N,N'-dioxide catalysts. The asymmetric induction achieved in the allylation was up to 99% ee. This procedure allows relatively simple, straightforward and efficient preparation of wide range of natural products. Keywords tiacumicin, asymmetric synthesis, allylation, catalysis, chiral Lewis bases, organocatalysis
|
|
|
Application of H-Bonding Catalysis in Organic Synthesis
Urban, Michal ; Veselý, Jan (advisor) ; Pour, Milan (referee) ; Šebesta, Radovan (referee)
Over the last 20 years, asymmetric synthesis has seen considerable progress, particularly in the field of catalysis. In addition to enzyme catalysis and transition metal catalysis, organocatalysis, catalysis using small organic molecules also plays an important role in the asymmetric synthesis. Chiral organocatalysts allow the preparation of structurally interesting and optically pure molecules via various activation modes. This work is focused on the use of organocatalysis based on the formation of hydrogen bonds in organic synthesis. Our study was devoted to the enantioselective organocatalytic reactions of ketimines leading to the formation of chiral vicinal centers. The first part deals with the organocatalytic enantioselective addition reaction of α- fluoro(phenylsulfonyl)methanes to ketimines derived from isatin. The reaction utilizes catalysis of a commercially available quinoline alkaloid cinchonine. A series of enantiomerically pure compounds were prepared containing two neighboring stereocenters in good yields of up to 97%, with diastereoselectivity up to 6: 1 dr and with enantiomeric excesses of 70-98% ee. In most cases pure diastereomers were obtained. In the second part of the work a method of enantioselective orgnocatalytic synthesis of bis-spirocompounds containing two neighboring...
|
|
|
Enantioselective synthesis of bispirocyclic compounds
Nigríni, Martin ; Veselý, Jan (advisor) ; Rýček, Lukáš (referee)
This diploma thesis is focused on synthesis of enantiomeric and diastereomeric pure bispirocyclic compounds via sequential Mannich/hydroamination reaction. The first part is focused on the optimization of reaction conditions of enantioselective asymmetric organocatalytic Mannich reaction of pyrazolone derivatives with isatin-derived ketimines. The enantiomerically enriched Mannich adducts were used in hydroamination cyclization. The second part of the work is focused on finding the suitable reaction conditions for performing the Mannich reaction and hydroamination as a sequential reaction leading to bispirocyclic compounds. The application of sequential reaction and selected transformations of bispirocyclic compounds was also performed. Key words Asymmetric synthesis, organocatalysis, Mannich reaction, hydroamination, sequential reaction, bispirocyclic coumpounds.
|
guest ::
