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Application of Pd-Catalyzed Reactions to the Synthesis of Lactones
Šnajdr, Ivan ; Pour, Milan (advisor) ; Kotora, Martin (referee) ; Opletalová, Veronika (referee)
Within the framework of this Thesis, a method fot the preparation of 3,6- disubstituted pyranones was developed and 15 final lactones were synthesized, and their cytostatic and antifungal activity was investigated. Principal steps in the preparation of the compounds were Yamaguchi-Hirao alkylation, hydroalumination followed by iodation and Pd- catalyzed carbonylative lactonization. None of the target compounds displayed interesting cytostatic or antifungal activity (IC50 < 10 μmol/L), which was suprising given the significant antifungal activity of analogous butenolides. The development of the synthesis of 3- monosubstituted pyranones is described next. Our strategy is based on the use of 5,6-dihydro-2H- pyran-2-one as the starting material, which was converted into the 3-iodo-5,6-dihydro-2H- pyran-2-one in one step. The key step of the synthesis was Pd-catalyzed Suzuki coupling. Finally, the preparation of α- and β-substituted-γ-alkylidenepentenolides is described. The target compounds exhibited significant cytostatic activity (IC50 < 5 μmol/L) against all tested tumor cells (CCRF-CEM, HeLa S3, HT 29, HL 60, L 1210).
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Reactions of Alkenes Iniciated by Transition Metals Alkyls and Hydrides
Nečas, David ; Kotora, Martin (advisor) ; Jindřich, Jindřich (referee) ; Starý, Ivo (referee) ; Mazal, Ctibor (referee)
l0 5. Conclusion 1) The first and practical catalýic method for smooth deallylation of 2-substituted-2-allylmalonates to 2-substituted malonates via selective cleavage of the C-C bond under mild reaction conditions has been developed' The reaction seems to be general with respect to the transition-metal complexes; however, the comparison of Ru and Ni catalysts indicates considerable differences in their specific activity and selectiviý. Last but not least, the smooth deallylation offers an opportuniý to use the allyl group as an effective protective group for acidic hydrogen of malonic esters. 2) It has been shown that it is possible to re-route the course of the reaction from c{ bond cleavage (deallylation) to c{ bond formation (cyclization) in Ni hydride cataryzed, reactions by a change in the amount of organoaluminium. It proceeded in high yields even in cases where deallylation could compete with cyclization (e.g. diallylmalonate, etc.) in high selectiviý. In addition, generation of Ni hydride species in sinr provides an effective means for fast and selective cyclization of variously substituted 1,6- heptadienes to cyclopentanes. Moreover, it is possible exert certain level of control for the preferential formation of methylidene(methyl)cyclopentanes or cyclopentenes by the appropriate choice of thb...
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Synthesis of helical molecules and their application in enantioselective catalysis
Krausová, Zuzana ; Starý, Ivo (advisor) ; Kotora, Martin (referee) ; Kvíčala, Jaroslav (referee) ; Hájíček, Josef (referee)
9. Summary We have prepared a set of helical compounds using a modular approach based on 12+2+21 cycloisomerisation of aromatic triynes under cobalt (l) catalysis. [7]helicene-like compound (P,S)-(+)-10, which represents a new structural type of possible liquid crystalline materials, was obtained in an optically pure form on a preparative scale. We have explored the diastereoselective synthesis as a general methodology for the preparation of functionalised helical compounds. A series of methoxy- and bromo-substituted helicene derivatives was successfully prepared with diastereoisomer ratios up to 100:0. ln addition, we have developed a practical synthesis of racemic heptahelicene rac-87. Optically pure heptahelicene (M)-(-)-87 and optically highly enriched (P)-(+)-87 were obtained by resolution of rac-87 by semipreparative HPLC on a chiral column. we have developed an original approach to the synthesis of phosphite ligands bearing helically chiral moieties, which were subsequently used in enantioselective catalysis, namely in hydroformylation reactions and allylic aminations. A series of hydroformylations of styrene, 4-chlorostyrene and vinyl acetate performed with Rh(acac)(co)2 under various conditions revealed that all helically chiral ligands under study afforded good to excellent regioselectivities....
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Synthesis of Specifically Substituted Heterocycles via Catalytic Reactions
Kratochvíl, Jiří ; Pour, Milan (advisor) ; Kotora, Martin (referee) ; Dvořák, Dalimil (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate Mgr. Jiří Kratochvíl Supervisor prof. RNDr. Milan Pour, Ph.D. Title of Doctoral Thesis Synthesis of Specifically Substituted Heterocycles via Catalytic Reactions This Ph.D. thesis deals with the synthesis of γ-alkylidene-α,β-unsaturated δ-lactones and lactams. Migita- Stille cross-coupling served as the key step in their preparation. Catalysis with palladium black was applied to the synthesis of the lactones and we demonstrated that it doesn't act as heterogeneous catalyst. Instead, it's only a precursor for catalytically active species, which is generated in situ and its true nature is unknown. The palladium nanoparticles are most likely responsible for the catalysis, although involvement of complexed atomic palladium cannot be excluded. Palladium black catalysis was also successfully applied to the synthesis of a series of structurally different substrates, which demonstrates its versatility and it was also proved that the catalyst can be easily recycled by simple filtration. An unusual Tsuji-Trost reaction then enabled transfer of the alkylidene substituent of the lactones to C5 furnishing polysubstituted heterocycles.
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