Colorectal cancer is the second most prevalent cancer form in both men and women in the Europe. In 2002, alimentary cancer (oesophagus, stomach, intestines) made up 26% of the annual incident cases of cancer amongst males in Europe, whereby about half of those were cancers of the colon and rectum (Eurostat 2002). Epidemiological evidence accumulating over the last decades indicates that besides a genetic disposition, diet plays a strong epigenetic role in the genesis of cancer. It is generally assumed that diet is causal for up to 80% of colorectal cancer (Bingham 2000). With the prospect of an approximated 50% rise in global cancer incidence over the first two decades of the 21st century, the World Health Organisation (WHO) has emphasized the need for an improvement in nutrition. Indeed there is increasing public health awareness with respect to nutrition. Today, living healthily is associated with less consumption of animal fats and red (processed) meat, moderate or no consumption of alcohol coupled with increased physical activity, and frequent intake of fruits, vegetables and whole grains (Bingham 1999; Johnson 2004). This idealogy partly stems from scientific epidemiological evidence supportive of an inverse correlation between the consumption of fruits and vegetables and the development cancer. Besides fibre and essential micro-nutrients like ascobate, folate, and tocopherols, the anti-carcinogenic properties of fruits and vegetables are generally thought to be rooted in the bioactivity of secondary plant components like flavonoids (Johnson 2004; Rice-Evans and Miller 1996; Rice-Evans 1995). Along with the increased public health awareness, has also come a burgeoning and lucrative dietary supplement industry, which markets products based on polyphenols and other potentially healthy compounds, sometimes with questionable promises of better health and increased longevity. These claims are based on accumulating in vitro and in vivo evidence indicating that flavonoids and polyphenols in fruits and vegetables can hinder proliferation, induce apoptosis of cancerous cells (Kern et al. 2005; Kumar et al. 2007; Thangapazham et al. 2007), act as antioxidants (Justino et al. 2006; Rice-Evans 1995) and influence cell signalling pathways (Marko et al. 2004; Joseph et al. 2007; Granado-Serrano et al. 2007), all of which are potential mechanisms proposed for their anti-carcinogenic activity. However, not only is the vast variety of supplements worrisome, but also problematic, is their easy accessibilty (just a click away on the internet) and the amount that can potentially be consumed. Such supplements are usually offered in pharmaceutical form (tablets, capsules, powder, concentrates) containing concentrations well beyond what is normally comsumable from the diet. For example, quercetin’s recommended intake is about 1g daily. However, estimates portend a possible daily increase of upto 1000 fold of the daily intake of quercetin (Hertog et al. 1995). Mindful of the concept of dose coined from the words of swiss scientist Paracelsus “What is it that is not poison? All things are poison and nothing is without poison. The right dose differentiates a poison and a remedy.” (“Alle Dinge sind Gift und nichts ist ohn’ Gift; allein die Dosis macht, dass ein Ding kein Gift ist”), it is thus conceivable that such high concentrations may not only reverse the acclaimed positive effects of flavonoids and polyphenols but also have negative effects thereby representing a health risk. The fact that direct evidence of the beneficial effects of flavonoids and polyphenols remains wanting, if not entirely lacking, coupled with the afore-mentioned marketing trend demands for a thorough examination of the possible adverse effects that may arise from increased consumption of flavonoids and polyphenols. The genesis and progression of cancer is usually accompanied by dysfunctional signalling of certain cell signalling pathways. Typical for colon carcinogenesis is the malfunctioning of the Wnt-signalling pathway, a pathway, which is crucial for the growth and development of normal colonocytes. The dysfunction of the Wnt-signalling pathway occurs in a manner that culminates in a proliferation stimulus of colonocytes, while differentiation is increasingly minimized. Hence, tumourigenesis is promoted. Interupting the proliferation stumuli by intervening in the actions of components of the Wnt-signalling pathway is one potential mechanism for the anti-carcinogenic action of flavonoids and polyphenols (Pahlke et al. 2006; Dashwood et al. 2002; Park et al. 2005). However, as previously hinted, the indulgence in the consumption of flavonoids and polyphenols based supplements could instead lead to a proliferation stimulus and provoke or promote carcinogenesis in normal cells or pre-cancerous cells respectively. The aim of this work was to
A series of (oligo)phenthiazines, thiazolium salts and sulfonic acid functionalized organic/inorganic hybrid materials were synthesized. The organic groups were covalently bound on the inorganic surface through reactions of organosilane precursors with TEOS or with the silanol groups of material surface. These synthetic methods are called the co-condensation process and the post grafting. The structures and the textural parameters of the generated hybrid materials were characterized by XRD, N2 adsorption-desorption measurements, SEM and TEM. The incorporations of the organic groups were verified by elemental analysis, thermogravimetric analysis, FT-IR, UV-Vis, EPR, CV, as well as by 13C CP-MAS NMR and 29Si CP-MAS NMR spectroscopy. Introduction of various organic groups endow different phsysical, chemical properties to these hybrid materials. The (oligo)phenothiazines provide a group of novel redox acitive hybrid materials with special electronic and optic properties. The thiazolium salts modified materials were applied as heterogenized organo catalysts for the benzoin condensation and the cross-coupling of aldehydes with acylimines to yield a-amido ketones. The sulfonic acid containing materials can not only be used as Broensted acid catalysts, but also can serve as ion exchangable supports for further modifications and applications.
The enamide moiety is an important substructure often encountered in biologically active compounds and synthetic drugs. Furthermore, enamides and their derivatives are versatile synthetic intermediates for polymerization, [4+2] cycloaddition, crosscoupling, Heck-olefinination, Halogenation, enantioselective addition or asymmetric hydrogenation. Traditional syntheses of this important substrate class involve rather harsh reaction conditions such as high temperatures and/or the use of strong bases. In continuation of our work on the addition of secondary amides to alkynes, we have developed a broadly applicable protocol for the catalytic addition of N-nucleophiles such as primary amides, imides and thioamides to terminal alkynes. The choice of ligands and additives determines the regiochemical outcome so that with two complementary catalyst systems, both the E-anti-Markovnikov products and the Z-anti-Markovnikov products can be synthesized highly regio- and stereoselectively.
It was recently reported that imatinib causes cell death in neonatal rat ventricular cardiomyocytes (NRVCM) by triggering endoplasmic reticulum (ER) stress and collapsed mitochondrial membrane potential. Retroviral gene transfer of an imatinib-resistant mutant c-Abl into NRVCM appeared to alleviate imatinib-induced cell death and it was concluded that the observed imatinib-induced cytotoxicity is mediated through direct interactions of imatinib with c-Abl. The imatinib effects were described as being specific for cardiomyocytes only, which are relevant also for the in vivo situation in man. [Kerkelä et al. 2006] The goal of the present study was to reproduce the published experiments and to further explore the dose-response relationship of imatinib-induced cell death in cardiomyocytes. Additional markers of toxicity were investigated. The following biochemical assays were applied: LDH release (membrane leakage marker), MTS-reduction (marker of mitochondrial integrity), ATP cellular contents (energy homoeostasis) and caspase 3/7 activity (apoptosis). The endoplasmatic reticulum (ER) stress markers eIF2α (elongation initiation factor 2α), XBP1 (X Box binding Protein 1), and CHOP (cAMP response element-binding transcription factor (C/EBP) homologous protein) were determined at the transcriptional and protein level. Online monitoring of cell attachment of, oxygen consumption and acidification of the medium by rat heart cells (H9c2) seated on chips (Bionas) allowed the determination of the onset and reversibility of cellular functions. Image analysis measured the spontaneous beating rates after imatinib treatment. The role of imatinib-induced reactive oxygen species was evaluated directly by 2’,7’-Dichlorofluorescein fluorescence and indirectly by means of interference experiments with antioxidants. The specificity of imatinib-induced effects were specific to cardiomyocytes was evaluated in fibroblasts derived from rat heart, lung and skin. The specific role of c-Abl in the imatinib-induced cellular toxicity was investigated by specific gene silencing of c-Abl in NRVCM. The results demonstrated that imatinib caused concentration-dependent cytotoxicity, apoptosis, and ER stress in heart, skin and lung fibroblasts, similar or stronger to those observed in cardiomyocytes. Similar to the results from cardiomyocytes, ER stress markers in fibroblasts were only increased at cytotoxic concentrations of imatinib. This effect was not reversible; also, reactive oxygen species did not participate in the mechanism of the imatinib-induced cytotoxicity in NRVCM. Small interfering RNA (siRNA)-mediated reduction of c-Abl mRNA levels by 51 % and c-Abl protein levels by 70 % had neither an effect on the spontaneous beating frequency of cardiomyocytes nor did it induce cytotoxicity, apoptosis, mitochondrial dysfunction or ER stress in NRVCM. Incubation of imatinib with c-Abl siRNA-transfected NRVCM suggested that reduced c-Abl protein levels did not rescue cardiomyocytes from imatinib-induced cytotoxicity. In conclusion, results from this study do not support a specific c-Abl-mediated mechanism of cytotoxicity in NRVCM.
Photochemical reactions are of great interest due to their importance in chemical and biological processes. Highly sensitive IR/UV double and triple resonance spectroscopy in molecular beam experiments in combination with ab initio and DFT calculations yields information on reaction coordinates and Intersystem Crossing (ISC) processes subsequent to photoexcitation. In general, molecular beam experiments enable the investigation of isolated, cold molecules without any influence of the environment. Furthermore, small aggregates can be analyzed in a supersonic jet by gradually adding solvent molecules like water. Conclusions concerning the interactions in solution can be derived by investigating and fully understanding small systems with a defined amount of solvent molecules. In this work the first applications of combined IR/UV spectroscopy on reactive isolated molecules and triplet states in molecular beams without using any messenger molecules are presented. Special focus was on excited state proton transfer reactions, which can also be described as keto enol tautomerisms. Various molecules such as 3-hydroxyflavone, 2-(2-naphthyl)-3-hydroxychromone and 2,5-dihydroxybenzoic acid have been investigated with regard to this question. In the case of 3-hydroxyflavone and 2-(2-naphthyl)-3-hydroxychromone, the IR spectra have been recorded subsequent to an excited state proton transfer. Furthermore the dihydrate of 3-hydroxyflavone has been analyzed concerning a possible proton transfer in the excited state: The proton transfer reaction along the water molecules (proton wire) has to be induced by raising the excitation energy. However, photoinduced reactions involve not only singlet but also triplet states. As an archetype molecule xanthone has been analysed. After excitation to the S2 state, ISC occurs into the triplet manifold leading to a population of the T1 state. The IR spectrum of the T1 state has been recorded for the first time using the UV/IR/UV technique without using any messenger molecules. Altogether it is shown that IR/UV double and triple resonance techniques are suitable tools to analyze reaction coordinates of photochemical processes.
The main focus of this dissertation is the synthesis and characterization of more recent zeolites with different pore architectures. The unique shape-selective properties of the zeolites are important in various chemical processes and the new zeolites containing novel internal pore architectures are of high interest, since they could lead to further improvement of existing processes or open the way to new applications. This dissertation is organized in the following way: The first part is focused on the synthesis of selected recent zeolites with different pore architectures and their modification to the acidic and bifunctional forms. The second part comprises the characterization of the physicochemical properties of the prepared zeolites by selected physicochemical methods, viz. powder X-ray diffractometry (XRD), N2 adsorption, thermogravimetric analysis (TGA/DTA/MS), ultraviolet-visible (UV-Vis) spectroscopy, atomic absorption spectroscopy (AAS), infrared (IR) spectroscopy, scanning electron microscopy (SEM), 27Al and 29Si magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy, temperature-programmed reduction (TPR), temperature-programmed desorption of pyridine (pyridine TPD) and adsorption experiments with hydrocarbon adsorptives. The third part of this work is devoted to the application of test reactions, i.e., the acid catalyzed disproportionation of ethylbenzene and the bifunctional hydroconversion of n-decane, to characterize the pore size and architecture of the prepared zeolites. They are known to be valuable tools for exploring the pore structure of zeolites. Finally, an additional test, viz. the competitive hydrogenation of 1-hexene and 2,4,4-trimethyl-1-pentene, has been applied to probe the location of noble metals in medium pore zeolite. The synthesis of the following zeolite molecular sieves was successfully performed in the frame of this thesis (they are ranked according to the largest window size in the respective structure): • 14-MR pores: UTD-1, CIT-5, SSZ-53 and IM-12 • 12-MR pores: ITQ-21 and MCM-68 • 10-MR pores: SSZ-35 and MCM-71 All of them were obtained as pure phase (except zeolite MCM-71 with a minor impurity phase that is hardly to avoid and also present in samples shown in the patent literature). The synthesis conditions are very critical with respect to the formation of the zeolite with a given structure. In this work, the recommended synthesis recipes are included. Among the 14-MR zeolites, the aluminosilicates UTD-1 (nSi/nAl = 28), CIT-5 (nSi/nAl = 116) and SSZ-53 (nSi/nAl = 55) with unidimensional extra-large pore opening formed from 14-MR rings exhibit promising catalytic properties with high thermal stability and they possess strong Brønsted-acid sites. By contrast, the germanosilicate IM-12 with a structure containing 14-MR channels intersecting with 12-MR channels is unstable toward moisture. It was found that UTD-1 and SSZ-53 zeolites are highly active catalysts for the acid catalyzed disproportionation of ethylbenzene and n-decane hydroconversion due to their high Brønsted acidity. To explore their pore structures, the applied two test reactions suggest that UTD-1, CIT-5 and SSZ-53 zeolites contain a very open pore system (12-MR or larger pore systems) because the product distributions are not hampered by too small pores. ITQ-21, a germanoaluminosilicate zeolite with a three-dimensional pore system and large spherical cages accessible through six 12-MR windows, can be synthesized with nSi/nAl ratios between 27 and >200. It possesses a large amount of Brønsted-acid sites. The aluminosilicate zeolite MCM-68 (nSi/nAl = 9) is an extremely active catalyst in the disproportionation of ethylbenzene and in the n-decane hydroconversion. This is due to the presence of a high density of strong Brønsted-acid sites in its structure. The disproportionation of ethylbenzene suggests that MCM-68 is a large pore (i.e., at least 12-MR) zeolite, in agreement with its crystallographic structure. In the hydroconversion of n-decane, the presence of tribranched and ethylbranched isomers and a high isopentane yield of 58 % in the hydrocracked products suggest the presence of large (12-MR) pores in its structure. By contrast, a relatively high value for CI* (modified constraint index) of 2.9 suggests the presence of medium (10-MR) pores in its structure. As a whole, the results are in-line with the crystallographic structure of MCM-68. SSZ-35, a 10-MR zeolite, can be synthesized in a broad range of nSi/nAl ratios between 11 and >500. This zeolite is interesting in terms of shape selectivity resulting from its unusual pore system having unidimensional channels alternating between 10-MR windows and large 18-MR cages. This thermally very stable zeolite contains both, strong Brønsted- and strong Lewis-acid sites. The disproportionation of ethylbenzene classifies SSZ-35 as a large pore zeolite. In the hydroconversion of n-decane, the suppression of bulky ethyloctanes and propylheptane clearly suggests the presence of 10-MR sections in the pore system. By contrast, the low CI* values of 1.2-2.3 and the high isopentane yields of 56-60 % in the hydrocracked products suggest that SSZ-35 also possesses larger intracystalline voids, i.e., the 18-MR cages. The results from the catalytic characterization are in good agreement with the crystallographic structure of zeolite SSZ-35. It was also found that the nSi/nAl ratio influences the crystallite size and therefore the external surface area. As a consequence, product selectivities are also influenced: The lowest nSi/nAl ratio or the smallest crystallite size sample produces larger amounts of the relatively bulky products. The formation of these products probably results from the higher conversion or they are preferentially formed on the external surface area of the catalyst. Zeolite MCM-71 (nSi/nAl = 8) possesses an extremely thermally stable structure and contains a high concentration of Brønsted-acid sites. Its structure allows for the separation of n-alkanes from branched alkanes by selective adsorption. MCM-71 exhibits unique shape-selective properties towards the product distribution in ethylbenzene disproportionation, which is different to those obtained in the medium pore SSZ-35 zeolite. All reaction parameters are fulfilled to classify MCM-71 as medium pore zeolite and this is in good agreement with its reported structure consisting of two-dimensional network of elliptical 10-MR channels and an orthogonal sinusoidal 8-MR channels. The competitive hydrogenation of 1-hexene and 2,4,4-trimethyl-1-pentene was exploited to probe that the major part of the noble metal is located inside the intracrystalline void volume of the medium pore zeolite SSZ-35.
A number of natural products are known that contain an enamide as a key structural feature. This functionality is a very important subunit in various biologically active products and pharmaceutical drug lead compounds. In addition, enamides serve as highly versatile synthetic intermediates, particularly in the pericyclic reaction, formation of heterocycles, cross-coupling and in asymmetric synthesis. As a result, several protocols have been devised for the preparation of enamides. Traditional syntheses include condensation of aldehydes and ketones with amides or from hydroxylamines and acetic anhydride, require harsh conditions and yield mixtures of E/Z products. Several metal catalyzed approaches have been also investigated, such as isomerization of N-allylamides and catalytic cross-coupling of amides with vinyl halides or pseudohalides. These protocols proceed under milder conditions but suffer from the limited availability of these starting materials. The research described in this dissertation focuses on efficient and atom-economic preparation of enamides and thioenamides, using readily available starting materials. We developed catalyst systems generated in situ from bis(2-methallyl)-cycloocta-1,5-diene-ruthenium(II), phosphines and Lewis acid or base, efficiently catalyze the addition of primary amides and thioamides to terminal alkynes with exclusive formation of the anti-Markovnikov products in high yield and stereoselectivity under mild reaction conditions. The generality of the newly developed methodologies is demonstrated by common functional group tolerance. Furthermore, Markovnikov products were formed via phosphine-catalyzed addition of cyclic amides to phenylacetylene derivatives. The hydroamidation protocol of primary amides was successfully used in the synthesis of naturally occurring compounds, such as alatamide, lansiumamide A, botryllamides C and E, and the key intermediate in the synthesis of aristolactam. In order to investigate the reaction mechanism, the addition of various amides and carboxylic acids to terminal alkynes was performed using deuterium labeled starting materials and followed by in situ NMR and GC-MS studies.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic and persistent organic pollutant, which is ubiquitously found in the environment. The prototype dioxin compound was classified as a human carcinogen by the International Agency for Research on Cancer. TCDD acts as a potent liver tumor promoter in rats, which is one of the major concerns related to TCDD exposure. There is extensive evidence, that TCDD exerts anti-estrogenic effects via arylhydrocarbon receptor (AhR)-mediated induction of cytochromes P450 and interferes with the estrogen receptor alpha (ERalpha)-mediated signaling pathway. The present work was conducted to shed light on the hypothesis that enhanced activation of estradiol metabolism by TCDD-induced enzymes, mainly CYP1A1 and CYP1B1, leads to oxidative DNA damage in liver cells. Furthermore, the possible modulation by 17beta-estradiol (E2) was investigated. The effects were examined using four different AhR-responsive species- and sex-specific liver cell models, rat H4II2 and human HepG2 hepatoma cell lines as well as rat primary hepatocytes from male and female Wistar rats. The effective induction of CYP1A1 and CYP1B1 by TCDD was demonstrated in all liver cell models. Basal and TCDD-induced expression of CYP1B1, which is a key enzyme in stimulating E2 metabolism via the more reactive formation of the genotoxic 4-hydroxyestradiol, was most pronounced in rat primary hepatocytes. CYP-dependent induction of reactive oxygen species (ROS) was only observed in rodent cells. E2 induced ROS only in primary rat hepatocytes, which was associated with a weak CYP1B1 mRNA induction. Thus, E2 itself was suggested to induce its own metabolism in primary rat hepatocytes, resulting in the redox cycling of catechol estradiol metabolites leading to ROS formation. In this study the role of TCDD and E2 on oxidative DNA damage was investigated for the first time in vitro in the comet assay using liver cells. Both TCDD and E2 were shown to induce oxidative DNA base modifications only in rat hepatocytes. Additionally, direct oxidative DNA-damaging effects of the two main E2 metabolites, 4-hydroxyestradiol and 2-hydroxyestradiol, were only observed in rat hepatocytes and revealed that E2 damaged the DNA to the same extent. However, the induction of oxidative DNA damage by E2 could not completely be explained by the metabolic conversion of E2 via CYP1A1 and CYP1B1 and has to be further investigated. The expression of low levels of endogenous ERalpha mRNA in primary rat hepatocytes and the lack of ERalpha in hepatoma cell lines were identified as crucial. Therefore, the effects of interference of ERalpha with AhR were examined in HepG2 cells, which were transiently transfected with ERalpha. The over-expression of ERalpha led to enhanced AhR-mediated transcriptional activity by E2, suggesting a possible regulation of E2 levels. In turn, TCDD reduced E2-mediated ERalpha signaling, confirming the anti-estrogenic action of TCDD. Such a modulation of the combined effects of TCDD with E2 was not observed in any of the other experiments. Thus, the role of low endogenous ERalpha levels has to be further investigated in transfection experiments using rat primary hepatocytes. Overall, rat primary hepatocyte culture turned out to be the more adaptive cell model to investigate metabolism in the liver, reflecting a more realistic situation of the liver tissue. Nevertheless, during this work a crosstalk between ERalpha and AhR was shown for the first time using human hepatoma cell line HepG2 by transiently transfecting ERalpha.
The present PhD thesis is mainly focused on synthesis, characterization and catalytic application of functionalized triphenylphosphine (TPP) ligands and their complexes. We developed a simple and effective strategy to immobilize TPP: A methylester group attached to one of the phenyl rings of TPP allowes the derivatization of the ligand with 3-trimethoxysilylpropylamine, a typical silane coupling agent used for the covalent immobilization of organic compounds on silica surfaces. The resulting functionalized TPP was further coordinated to Pd, Rh and Ru precursors to achieve homogeneous complexes which can be tethered on silica by the post synthetic grafting method and co-condensation method. The obtained heterogeneous catalysts exhibited excellent activity, selectivity and reusability in Suzuki, hydrogenation and transfer hydrogenation reactions. In order to investigate the stability of the catalysts, different types of characterizations such as TEM, solid state NMR of the used catalysts as well as AAS of filtrate and leaching tests were carried out. The results prove the practicability and efficiency of our method. This strategy was further modified to generate an anionic side chain linked to the TPP core by simply replacing the trimethoxysilylpropylamine group by sodium(3-amino- 1-propanesulfonate), which allowes the immobilization on imidazolium modified SBA-15 through electrostatic interaction. The obtained material was further reacted with PdCl2(CNPh)2 and the resulting hybrid material was used for the hydrogenation of olefins allowing mild reaction conditions. The catalyst shows excellent activity, selectivity and stability and it can furthermore be reused for at least ten times without any loss of activity. TEM images of the used catalyst clearly show the absence of palladium nanoparticles, proving the high stability of the palladium compound. By AAS no palladium could be detected in the products and further leaching tests very- fied the reaction to be truly heterogeneous. This concept of non-covalent immobili- zation guarantees a tight bonding of the catalytically active species to the surface in combination with a high mobility, which should be favorable for other catalyses.
In the 1st project, successful development of 2nd generation of a palladium catalyst for the selective hydrogenation of carboxylic acids to aldehydes was accomplished. This project was done in cooperation with Dipl. Chem. Thomas Fett from Boeringer Ingelheim, Austria. The new catalyst is highly effective for the conversion of diversely functionalized aromatic, heteroaromatic and aliphatic carboxylic acids to the corresponding aldehydes in the presence of pivalic anhydride at 5 bar hydrogen pressure, which was otherwise achieved either at 30 bar of hydrogen pressure or by using waste intensive hypophosphite bases as reducing agent. Our method has increased the synthetic importance of this valuable transformation. Selective hydrogenation of carboxylic acids to the corresponding aldehydes is now possible with industrial hydrogenation equipment as well as laboratory scale glass autoclaves. It might also convince the synthetic organic chemists to use this transformation for routine aldehyde synthesis in the laboratories.
In the 2nd project, a microwave assisted Cu-catalyzed protodecarboxylation of arenecarboxylic acids to arenes is achieved. This work was done in collaboration with Dipl. Chem. Filipe Manjolinho under the supervision of Dr. Nuria Rodríguez. In the presence of 1-5 mol% of inexpensive CuI/1,10-phenanthroline catalyst generated in situ under microwave radiations, diversely functionalized arenes and heteroarene carboxylic acids have been decarboxylated to the corresponding arenes in good yields at 190 °C in 5-15 min. The loss of volatile arenes with the release of CO2 is controled by the use of sealed high pressure resistant microwave vessels. These reactions are highly beneficial for parallel synthesis in drug discovery due to their short reaction time. Microwave technology will also help in the future to develop more effective catalysts for protodecarboxylation rections.
Based on the microwave assisted protodecarboxylation strategy, decarboxylative coupling of arenecarboxylic acids with aryl triflates and tosylates was also conducted under microwave radiation which provided higher yields of the corresponding biphenyls from deactivated substrates in short reaction time compared to the conventional heating.
In the 3rd project, crystalline, potassium (trifluoromethyl)trimethoxyborate was successfully applied for the synthesis of benzotrifluorides under the oxidative conditions. This project was done in cooperation with Dipl. Chem. Annette Buba. In the presence of Cu(OAc)2 and molecular oxygen, arylboronates were coupled with K+[CF3B(OMe)3] in DMSO at 60 °C. A variety of benzotriflurides was synthesized in good yields under the optimized reaction conditions. This protocol for the oxidative trifluoromethylation of arylboronates is the base for the development of decarboxylative trifluoromethylation reaction of arenecarboxylic acids.
The 4th project discloses the simple and straightforward synthesis of trifluoromethylated alcohols by nucleophilic addition of potassium (trifluoromethyl)trimethoxyborate to carbonyl compounds. This project was done in cooperation with Dr. Thomas Knauber and Dipl. Chem. Annette Buba. In the presence of K+[CF3B(OMe)3] in THF at 60 °C, diversely functionalized aldehydes and ketones were successfully converted into the corresponding trifluoromethylated alcohols.
The 3rd and 4th projects demonstrate the successful establishment of crystalline and shelf stable potassium (trifluoromethyl)trimethoxyborate as highly versatile CF3-source in nucleophilic trifluoromethylation reactions. These new protocols are characterized by their user-friendliness and broad applicability under mild reaction conditions, thus they are beneficial for late stage introduction of CF3-group into organic molecules.