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Enantioselective synthesis of bispirocyclic compounds
Nigríni, Martin
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.
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Synthesis of spirocyclic compounds containing quaternary carbon centres
Výbošťoková, Júlia ; Matoušová, Eliška (advisor) ; Baszczyňski, Ondřej (referee)
The main focus of this bachelor thesis is the preparation of spirocyclic compounds containing quaternary carbon centres. The key steps of the synthesis were palladium catalysed tandem cyclisation/Suzuki cross-coupling and subsequent halocarbocyclisation. The next step was oxidative opening of the tetrahydrofuran ring and following derivatisation of the resulting spirocyclic products. The prepared spirocyclic compounds will be tested for their possible cytotoxic effects. The first part of this work describes the preparation of starting materials which were subsequently subjected to the tandem cyclisation/Suzuki cross-coupling and halocarbocyclisation to form a quaternary carbon centre. In the second part, various oxidative conditions for tetrahydrofuran ring opening to form spirocyclic compounds are discussed. The last part of this work deals with the derivatisation of the synthesised spirocycles. Keywords: synthesis, spirocyclic compounds, quaternary carbon centres, cytotoxicity
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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
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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...
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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.
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The use of alkylideneheterocycles for the synthesis of spirocyclic compounds
Vopálenská, Andrea ; Veselý, Jan (advisor) ; Matoušová, Eliška (referee)
This bachelor thesis is focused on the stereoselective Michael-alkylation reaction of alkylidene heterocycles using bifunctional organocatalysis. Within the thesis, suitable starting materials were first prepared and then the organocatalytic reaction leading to the formation of spirocyclic compounds was optimized. Under optimized conditions, a study of the scope of application of the method on selected derivatives was also performed and the optical purity of the products was determined. Key words Organocatalysis, asymmetric synthesis, cascade reaction, Michael reaction, bifunctional organocatalysts, spirocyclic compounds
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Enantioselective synthesis of spiro compounds
Urban, Michal ; Veselý, Jan (advisor) ; Kotora, Martin (referee)
This thesis deals with the preparation of enantiomerically and diastereomerically pure spirocompounds using asymmetric organocatalysis. The first part is focused on the enantioselective synthesis of spirocompounds by organocatalytic reaction of α,β-unsaturated aldehydes with sulfur heterocyclic compounds catalysed with secondary amines. It is a domino Michael/Michael/aldol reaction using iminium and enamine activation. The second part is focused on the subsequent transformation of the prepared spirocompounds.
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