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New Carbanion Rearrangement of Sulfur Compounds and Its Application
Řehová, Lucie ; Jahn, Ullrich (advisor) ; Cibulka, Radek (referee) ; Jindřich, Jindřich (referee)
New Carbanion Rearrangement of Sulfur Compounds and Its Application Abstract This thesis reports the investigation of an unusual reversal in the metalation selectivity of alkyl aryl sulfones and sulfoxides and its application. Such compounds undergo initial directed ortho-metalation at −78 řC despite having an acidic α-hydrogen atom and the resulting aryllithiums rearrange subsequently completely to the initially expected α-sulfonyllithiums on warming. The scope and the limitations for this process were identified. Both carbanion types of sulfones were applied in reactions with various electrophiles. α-Lithiated sulfones generated upon the transmetalation process were used in Julia olefinations. A mechanistic study of the course of the transmetalation reaction is presented. The kinetics of the transmetalation were determined. Investigations concerning the concentration dependence, proton transfer equilibria between the different ortho-sulfonyllithium intermediates and crossover experiments provided the evidence that a concerted intermolecular pathway prevails. On this basis a new integrated synthetic approach to naturally occurring iridoids was developed. It is based on a tandem alkoxycarbonylation/oxidative radical cyclization of the olefins synthesized by the Julia reaction after the investigated...
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New Thermal and Oxidative Radical Cyclization Methodology and Application to the Total Synthesis of Bridged Diketopiperazine Alkaloids
Amatov, Tynchtyk ; Jahn, Ullrich (advisor) ; Pour, Milan (referee) ; Cibulka, Radek (referee)
This thesis describes the development of new thermal and oxidative radical cyclization methodologies and their application to the total syntheses of alkaloids, particularly to bridged diketopiperazine (DKP) alkaloids. A practical solvent free approach to diverse DKPs and quinazolines is described. The methodology proceeds by thermal silica gel mediated deprotection of the Boc protecting group and intramolecular condensation of the resulting free dipeptides and tripeptides. It was applied to the total syntheses of alkaloids glyantrypine and ardeemin. A major part of the thesis concerns with the discovery and applications of novel diketopiperazine derived alkoxyamines. Their propensity to undergo facile thermal C-O bond homolysis to generate captodative DKP radicals and persistent TEMPO radical allowed using them as radical surrogates. The methodology takes advantage of the persistent radical effect (PRE). The methodology based on PRE was applied in an asymmetric approach to the alkaloid asperparaline C. An asymmetric synthesis of a very advanced precursor to asperparaline C, 8- oxoasperparaline C, was accomplished in 11 steps and 15% overall yield. The key steps of the synthesis include a direct oxidative cyclization of DKPs, regioselective furan dearomatization with singlet oxygen and a reductive...
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Total Synthesis of (-) - Methoxyestrone
Betík, Robert ; Kotora, Martin (advisor) ; Dvořák, Dalimil (referee) ; Jahn, Ullrich (referee)
English Abstract The new diastereoselective synthesis of estrone precursor and enantioselective synthesis of (-)-methoxyestrone are described in this work. The diastereoselective synthesis was based on 2 Bu2ZrCp2 mediated reactions followed by Pauson-Khand cyclocarbonylation. The sequence of reactions yielded 16-keto-17-methylestratetraene, compound with tetracyclic steroid framework, with excellent diastereoselectivity. Synthesis was finished with chemoselective reduction of the keto group in 16-keto-17-methylestratetraene to furnish 17- methylestratetraene, which is known precursor of estrone. The enantioselective synthesis was based on a conjugate addition of vinylmagnesium bromide to aldimine formed from 1-formyl- 3,4-dihydro-6-methoxynaphthalene and (L)-t-leucine t-butyl ester, which afforded crucial chiral intermediate 1-formyl-3,4-dihydro-6-methoxy-2-vinyl-naphthalene with very high ee > 98 %. Further transformations led to the construction of alkyl side chain containing triple bond and finally, the Pauson-Khand cyclocarbonylation followed by chemoselective reduction of carbonyl group gave estrone precursor, which was converted to (-)- methoxyestrone according known procedure.
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1,3-Dialkyl-4,5-dymethylimidazol-2-ylidene Amines as a New Class of Strong Electron Donors in Design and Synthesis of Organosuperbases and Stable Cations
Kunetskiy, Roman ; Jahn, Ullrich (advisor) ; Hájíček, Josef (referee) ; Kvíčala, Jan (referee)
Roman A. Kunetskiy Syntéza organosuperbazí a stabilních kationtů na bázi 1,3-dialkyl-4,5-dimethylimidazol- 2-ylidenaminů jako nového druhu silných elektron-donorů / 1,3-Dialkyl-4,5- dimethylimidazol-2-ylidene Amines as a New Class of Strong Electron Donors in Design and Synthesis of Organosuperbases and Stable Cations Abstrakt Byla vyvinuta jednoduchá a efektivní metoda pro zavedení nové silně elektron-donorní 1,3-dialkyl-4,5-dimethylimidazol-2-yliden aminové skupiny (IMAM) do různých organických molekul za použití 2-fluorimidazoliových nebo 2-chlorimidazoliových solí. Touto metodou byly syntetizovány a studovány tři nové druhy katalyzátorů fázového přenosu a dva nové druhy stabilních nefosforných organických superbazí (SB). Vybrané katalyzátory fázového přenosu se ukázaly velice stabilní vůči hydrolýze za různých silně bazických podmínek. Byla studována velmi vysoká bazicita připravených SB v roztoku či v plynné fázi a bylo zjištěno, že je způsobena aromatizací a uvolněním sterického napětí po protonaci. Byla vyvinuta nová efektivní metoda pro aminaci 1,3-dialkylimidazol-2-ylidenů a tris(dimethylamino)fosfinu terc-butylazidem. Byla určena bazicita nových vysoce stericky bráněných 1,3-di-terc-butyl- 4,5-dimethylimidazol-2-ylidenů, pKBH + (DMSO) = 24.8. Abstract Simple and efficient method for the...
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Diastereoselective synthesis of helically chiral compounds for enantioselective catalysis
Andronova, Angelina ; Stará, Irena (advisor) ; Jahn, Ullrich (referee) ; Kvíčala, Jan (referee)
Cílem disertační práce bylo vyvinout syntetický přístup k opticky čistým helicenům. Ty mohou být připraveny rezolucí racemátů nebo pomocí asymetrické syntézy. V této práci byla rozpracována diastereoselektivní a enantioselektivní intramolekulární [2+2+2] cyklotrimerizace aromatických triynů. Diastereoselektivní cyklotrimerizace využívala jako substráty opticky čisté triyny, které poskytovaly helicenová analoga v diastereomerní čistotě >99% de. Při enantioselektivní niklem katalyzované cyklotrimerizaci achirálních triynů bylo dosaženo až 40% ee. Opticky čisté helikální fosfiny a fosfity, které byly připraveny pomocí diastereoselektivní syntézy, byly následně testovány v enantioselektivní katalýze. Byl vypracován syntetický přístup k helicenovým analogům s fosforovou skupinou v různých polohách. Byl studován vliv substituce na terminální trojné vazbě na průběh cyklotrimerizace. Nebyla prokázána jasná závislost mezi elektronovou povahou aromatických substituentů s různými elektrondonorními a elektronakceptorními skupinami a výtěžkem cyklotrimerizace. Nicméně bylo zjištěno, že v přítomnosti arylových substituentů vznikají přednostně (P)-heliceny a při jejich absenci (M)-heliceny. Pomocí dvojnásobné intramolekulární cyklotrimerizace byl připraven thia[9]helicen, který byl následně studován...
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The Combination of Organometallic, Transition-Metal Catalyzed, Radical and Carbocationic Reaction Steps to Domino Processes
Jagtap, Pratap Ramling ; Jahn, Ullrich (advisor) ; Tobrman, Tomáš (referee) ; Bureš, Filip (referee)
This work deals with the development of methodology, which couples reactive intermediates of varying oxidation states, in tandem sequences comprising 1,2-organometallic addition/transition metal catalyzed isomerization/Michael addition/SET oxidation/radical cyclization/oxygenation steps in the synthesis of highly functionalized carbocycles. Implementation of this sequence being catalytic in the SET oxidant was studied. 1,4-Diketones were synthesized in a tandem 1,2-addition/ruthenium-catalyzed redox isomerization/enolates oxidation/radical dimerization reaction and results were compared with 1,4-diketones formation via oxidative coupling of ketone enolates. The total synthesis of selective tetrahydrofuran lignans from 1,4-diketones obtained in a tandem addition/isomerization/dimerization reaction is also documented
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