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| 2. |
- Bartholomeyzik, Teresa, 1984-
(författare)
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Palladium(II)-Catalyzed Oxidative Carbocyclization/Functionalization of Allenynes
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The selective formation of carbon-carbon bonds constitutes a key transformation in organic synthesis with useful applications in pharmaceutical or material industry. A particularly versatile tool for carbon-carbon as well as carbon-heteroatom bond formation is palladium catalysis, which allows for mild and selective routes even towards complex structures.The work in this thesis describes the development and the mechanistic investigation of a palladium(II)-catalyzed oxidative carbocyclization/functionalization methodology, which converts 1,5-allenynes into either arylated or borylated carbocycles. To this end, either boronic acids or B2pin2 are employed and 1,4-benzoquinone serves as the stoichiometric oxidant. These protocols provide access to two products, a cyclic triene and a cyclic vinylallene. Their formation is dependent on the substrate structure as the latter product requires a propargylic C–H bond to be present in the substrate. Based on kinetic isotope effects, mechanisms involving either an initial allenic or propargylic C–H abstraction, respectively, were proposed. Full control of product selectivity to give either trienes or vinylallenes was achieved by modifying the reaction conditions with additives. Using substoichiometric amounts of BF3·OEt2 leads selectively to borylated or arylated vinylallenes. Under arylating conditions the reaction is zero order in allenyne and oxidant, and first order in phenylboronic acid. Transmetalation and, to some extent, propargylic C–H cleavage were found to be turnover-limiting. The selective reaction towards functionalized trienes was achieved by addition of either substoichiometric LiOAc·2H2O (borylation) or excess amounts of H2O (arylation). For the latter case, a kinetic study revealed an unusually slow catalyst activation. Lower concentrations of H2O gave product mixtures, and it was shown that vinylallenes are formed with either boronic acid or boroxine, whereas the formation of trienes requires boronic acid.
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| 3. |
- Borén, Linnéa, 1978-
(författare)
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Enantioselective Synthesis of Sec-Alcohol Derivatives and Diols via Combined Ruthenium and Enzyme Catalysis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first part of this thesis describes the synthesis of enantiopure secondary alcohol derivatives. These syntheses are carried out via the combination of an enzyme as a resolution catalyst and a ruthenium catalyst as a racemization catalyst, in what is called dynamic kinetic resolution (DKR). By varying the resolution catalyst enantio-complementary processes can be obtained. A lipase (PS-C II) catalyzed DKR of γ-hydroxyamides gave the corresponding (R)-acetates in high yields and with high enantioselectivity. The synthetic usefulness of these obtained (R)-acetates was demonstrated by the synthesis of (R)-5-methyltetrahydrofurane-2-one. A protease (Subtilisin Carlsberg) catalyzed DKR of various secondary alcohols gave the corresponding (S)-acetates in high yields and with high enantioselectivity. In the second part of this thesis the DKR process has been extended into a dynamic kinetic asymmetric transformation (DYKAT) of diols. Various 1,5- and 1,4-diols were transformed into enantiopure diacetates in a lipase (CALB and PS-C II) catalyzed DYKAT. The synthetic utility of the obtained enantiopure diacetates were demonstrated by the synthesis of various enantiopure disubstituted heterocycles.
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| 4. |
- Csjernyik, Gábor, 1974-
(författare)
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Studies of Biomimtic Oxidations and Racemizations
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with studies of ruthenium-catalyzed hydrogen transfer reactions for oxidations and racemization.Through optimisation of the substrate-selective redox catalyst, the electron and proton transfer mediator (a benzoquinone derivative), and the oxygen-activating metal macrocycle a highly efficient biomimetic oxidation of secondary alcohols was obtained. Several alcohols were subjected to the new oxidation protocol and the corresponding ketones were isolated in high yield.The deactivation of the oxygen-activating metal macrocycle retarded the aerobic oxidation of primary alcohols. Encapsulation of the metal macrocycle into zeolite, described in chapter 3, proved to be an efficient method to solve this problem and comparable conversion of alcohols was achieved. The immobilization of the oxygen-activating porphyrin to a surface can be an alternative approach to solve the deactivation problem. Therefore as the first step towards studies of immobilized porphyrins on a metal surface (of gold or silver), S-thioacetyl derivatized porphyrins were synthesized; two alternative syntheses are described in chapter 4.A new and effecient ruthenium-catalyzed racemization protocol was established by proper ligand tuning. The racemization of the enantiomerically pure alcohols was increased significantly; this work is reported in chapter 5.
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| 6. |
- Eriksson, Kristofer, 1983-
(författare)
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Development and Applications of Surface-Confined Transition Metal Complexes : Heterogeneous Catalysis and Anisotropic Particle Surfaces
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main focus of this thesis has been directed towards developing novel surface-confined transition metal complexes for applications in heterogeneous catalysis and for the preparation of anisotropic particle surfaces. The first part describes the heterogenization of a homogeneous transition metal-based catalyst tetraphenyl cobalt porphyrin (CoTPP) on silicon wafers and on silica particles. The activity in hydroquinone oxidation for the silica particle-immobilized CoTPPs was found to be increased 100-fold compared to its homogeneous congener whereas the silicon wafer-immobilized CoTPPs achieved lower activity due to the formation of clusters of catalyst molecules on the support surface as detected with atomic force microscopy (AFM). The second part of this thesis describes the development and characterization of anisotropic particle-surfaces by electrochemical site-specific oxidation of surface-confined thiols. Reactive patches or gold gradients could be obtained on the particle surfaces depending on the type of working electrode used and on the electrolyte composition. The particle surface functionalities were characterized with X-ray photoelectron spectroscopy (XPS) and the particle-surface-confined patches and gradients were conjugated with proteins to obtain fluorescence for investigation using fluorescence microscopy. Gold-functionalized siliceous mesocellular foams were further demonstrated to be highly efficient and selective catalysts in the cycloisomerization of 4-alkynoic acids to lactones. The final part of this thesis describes the preparation and characterization of palladium nanoparticles heterogenized in the pores of siliceous mesocellular foam. The nanoparticles were analyzed with transmission electron microscopy (TEM) and found to have a size of 1-2 nm. Primary- and secondary benzylic- and allylic alcohols were oxidized by the heterogeneous palladium nanoparticles in high to excellent yields using air atmosphere as the oxygen source. The nanopalladium catalyst was used up to five times without any decrease in activity and the size of the nanoparticles was retained according to TEM.
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| 7. |
- Guðmundsson, Arnar, 1990-
(författare)
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Iron-Catalyzed Reactions and X-Ray Absorption Spectroscopic Studies of Palladium- and Ruthenium-Catalyzed Reactions
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The focus of this thesis is twofold: The first is on the application of iron catalysis for organic transformations. The second is on the use of in situ X-ray absorption spectroscopy (XAS) to investigate the mechanisms of a heterogeneous palladium-catalyzed reaction and a homogeneous ruthenium-catalyzed reaction.In chapters two, three and four, the use of iron catalyst VI, or its analog X, is described for (I) the DKR of sec-alcohols to produce enantiomerically pure acetates; (II) the cycloisomerization of α-allenols and α-allenic sulfonamides, giving 2,3-dihydrofuran or 2,3-dihydropyrrole products, respectively, with excellent diastereoselectivity; and (III) the aerobic biomimetic oxidation of primary- and secondary alcohols to their respective aldehydes or ketones.In the fifth chapter, XAS is used to elucidate the mechanisms of a Pd(II)-AmP-MCF-catalyzed lactonization reaction of acetylenic acids. The catalyst was known to deactivate during the reaction and the XAS studies identified the cause of this deactivation. A reactivation strategy was subsequently developed based on these findings.In the sixth and final chapter, XAS is used to examine the activation mechanism of a ruthenium racemization catalyst and a ruthenium-acyl intermediate which had previously been speculated to be formed in the activation process was confirmed.
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| 8. |
- Gustafson, Karl P. J., 1986-
(författare)
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Studies on Metalloenzymatic Dynamic Kinetic Resolutions and Iron-Catalyzed Reactions of Allenes
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main focus of this thesis lies in the development of new transition metal-catalyzed chemoenzymatic dynamic kinetic resolutions (DKR) of both alcohols and amines. The first part of the thesis deals with the development of new heterogeneous systems for the DKR of amines. The racemization catalysts in these different systems are all composed of palladium nanoparticles supported on either mesoporous silica or incorporated in a biocomposite that is composed of a bioactive cross-linked enzyme aggregate. The second part of the thesis deals with the development of a homogeneous iron catalyst in the racemization of sec-alcohols for the implementation in a chemoenzymatic DKR. Two protocols for the racemization of sec-alcohols are reported. The first one could not be combined with a chemoenzymatic kinetic resolution, although this was overcome in the second iron based protocol. Following the successful iron catalyzed chemoenzymatic DKR of sec-alcohols, the iron catalyst was used in the cyclization of α-allenic alcohols and N-protected amines to furnish 2,3-dihydrofurans and 2,3-dihydropyrroles, respectively. The cyclization is proceeding in a diastereoselective manner.The last part of the thesis deals with attempts to further elucidate the mechanism of activation of a known ruthenium racemization catalyst. X-ray absorption spectroscopy using synchrotron radiation was used for this purpose.
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| 9. |
- Görbe, Tamás, 1988-
(författare)
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Heterogeneous catalysis in racemization and kinetic resolution along a journey in protein engineering
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first part of my thesis concerns the use of heterogeneous acidic resins for racemization of tert-alcohols without any side-product formation. The focus was to develop a system which can be further extended to a DKR protocol consisting of an enzymatic KR reaction. Based on our knowledge of the resins, an unexpected migratory DKR protocol turned out to be an efficient method for the synthesis of carbocyclic allylic carbinols.The development of enzyme and metal catalyst hybrids was already an ongoing theme in our group. A supporter-free biohybrid catalyst was developed which can be used in several different types of reactions. The Pd(0)-CalB CLEA catalyst was applied in a two-step-cascade transformation and in the DKR of benzylic primary amines. The catalyst was characterized by different analytical techniques, to understand its composition and structure.The enzymes have always been the main focus of the studies and therefore wild type enzymes were initially utilized. However, these natural biocatalysts are associated with certain limitations. In contrast, protein engineering allows for enzymes to be modified and optimized. We have used the technique to create a subtilisin Carlsberg mutant, which was studied both by modeling and in vitro. The mutant was found to catalyze the (S)-selective transesterification of sec-alcohols containing long aliphatic carbon chains, and it also exhibited higher performance in organic solvent.The last project concerned the protein engineering of CalA enzyme towards tert-alcohols. The kinetic resolution of tert-alcohols with this enzyme is very slow but it occurs with good enantioselectivity. The aim was therefore to improve the activity of CalA via protein engineering. Seven amino acids were mutated close to the active site and a library was created based on our prediction. Throughout the screening, a few variants showed higher activity, which were sequenced and further analyzed in the transesterification of tert-alcohols.
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| 10. |
- Horváth, Attila, 1975-
(författare)
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Palladium(II)-Catalyzed Reactions of Allenes with Lithium Bromide and Cyclization of α-Amino Allenes to Pyrrolines
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on three novel palladium(II)-catalyzed reactions of allenes with lithium bromide and a bromonium ion induced cyclization of allenyl amides to pyrrolines. In Paper I a 1,2-functionalization of allenes is presented where bromide adds as a first nucleophile followed by intramolecular attack by an oxygen or nitrogen nucleophile. Chapter 2 deals with the extension of this reaction to different nitrogen nucleophiles such as urea, carbamate, and N-tosyl carbamate providing access to substituted pyrrolidines and oxazolidines in good yields under mild reaction conditions.Paper II deals with a stereoconvergent, palladium(II)-catalyzed SN2’ reaction of α-acetoxy allenes with bromide as nucleophile. In this reaction substituted (Z,E)-2-bromo-1,3-dienes are produced in good yields with excellent diastereo-selectivity.Paper III describes a mild racemization reaction of chiral allenes. The effect of the functional group present in the molecule on the reaction rate is examined. All these reactions published in Papers I-III proceed through a common intermediate: a 2-bromo-(π-allyl)palladium complex.The fourth paper describes a simple, efficient, and enantiocontrolled cyclization of N-protected α-allenyl amines with N-bromosuccinimide (NBS) to afford 3-bromo-pyrrolines. The synthesis of optically active 2,5-dehydroprolinol derivative is also described. The mechanism, scope, and limitations of all four reactions are discussed in this thesis.
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