Asymmetric catalysis

The use of Rh catalysts derived from a phospholane‐phosphite ligand were found to be more productive than the classic rhodium/BINAP system in enantioselective conjugate additions. These catalysts enable the use of lower amounts of aryl boronic acid in an asymmetric arylation reaction that required an impractical excess of nucleophile. This catalyst was also found to enable the coupling of a poorly reactive Michael acceptor, N‐CBz‐2‐3‐dehydro‐4‐piperidone, or the coupling of poorly reactive 2‐furyl boronic acids at ambient or near temperatures.

γ-Methyl-α-(alkylidene substituted)-γ-butyrolactones have been synthesized in two steps. The anion of allyl phosphonate 1 is condensed with different carbonyl compounds to afford α,βunsaturated esters 2a-g which are cyclised using 6N HCl to give title compounds.

The first di-μ-amidate dipalladium complexes and a new di-μ-carboxylate dipalladium complex of the COP (cobalt oxazoline palladacycle) palladium(II) catalyst family are reported and characterized crystallographically. The di-μ-amidate complex 3 or its enantiomer (ent-3) are the first asymmetric catalysts that allow commercially available, or readily accessible, (E)-2-alkene-1ols to be transformed to enantioenriched branched allylic aryl ethers upon reaction of their trichloroacetimidate derivatives with phenols. The 3-aryloxy-1-alkene products are formed in high enantiomeric purity (typically 90-98% ee) and useful yields (61-88%).

Chiral amide derived from (1S, 2R)-(+)-norephedrine and 2-furoic acid was found to catalyse the asymmetric Reformatsky reaction between prochiral aldehydes and α-bromo ethylacetate with diethylzinc as zinc source. The corresponding chiral β-hydroxy esters were formed in 99% yield with over 80% enantiomeric excess. The presence of air was found to be essential for the effective C-C bond formation. The mechanism for the catalytic reaction was proposed.

Shogaols, the pungent principle of ginger, exhibit interesting bioactivities. Practical preparation of shogaols is highly desired. Here we report the protection/deprotection-, salt-, and metalfree synthesis of shogaol in three steps by use of dimethylammonium dimethyl carbamate (DIMCARB), in which DIMCARB smoothly promoted Mannich-type condensation of the ketone donor with the aldehyde acceptor through the iminium cation intermediate.

In this report, it is demonstrated that chiral vinyl aziridines can be stereospecifically ring expanded. This synthetic approach allows controlled access to chiral 2,5-cis or 2,5-trans-3pyrroline products from starting materials with the appropriate aziridine geometry. Twenty three ring expansion examples, most of which feature a stereospecific cyclization, are presented.

The Diels-Alder reaction of 1-aminovinylphosphonate esters has been studied for the first time as a suitable procedure leading to quaternary carbocyclic α-aminophosphonates. The reaction is influenced by steric effects at the phosphonate functionality (bulky groups hinder the reaction) and electronic effects at the amino group (electron-withdrawing substituents increase the reaction rate). The exo/endo ratio is constant, and no influence of the solvent is observed. The experimental results have been rationalized by DFT methods.

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Polyamino acids, such as polyleucine, behave as synthetic enzymes in the asymmetric epoxidation of chalcone and other electron-deficient alkenes (the Julia `-Colonna reaction). The influences of reaction conditions, of the molecular structure of the catalysts and of the scaling-up of the process on the enantioselectivity of the reaction have been determined. The kinetics and mechanism have been investigated using a soluble PEG-polyleucine conjugate, which behaves in a similar way to an enzyme, showing saturation kinetics for both chalcone and HOO K . Enantioselective catalysis is achieved with peptides with as few as five residues and scalemic catalysts show high chiral amplification. Here, we discuss the relevance of these-enzyme like catalysts to prebiotic processes, such as the role of small peptides in the formation of optically active cyanohydrins.

Here we report that chiral Mn(I) complexes are capable of H-P bond activation. This activation mode enables a general method for the hydrophosphination of internal and terminal α,β-unsaturated nitriles. Metal-ligand cooperation, a strategy previously not considered for catalytic H-P bond activation, is at the base of the mechanistic action of the Mn(I)-based catalyst. Our computational studies support a stepwise mechanism for the hydrophosphination and provide insight into the origin of the enantioselectivity.

This article provides a short overview of the successful industrial-scale introduction of a new and demanding chemical process at Kaisten (Switzerland). A list of probably the most important criteria that prompted management to decide in favour of this location at that time is given.

A group of modified (salen)Cr(III)Cl complexes with bulky benzylic substituents in the 3,3′-position of the salicylidene moiety have been successfully applied for the asymmetric nitroaldol reaction. The readily accessible complex bearing 3-phenylpent-3-yl groups (2 mol %) leads to β-nitro alcohols in up to 92% yield and 94% ee.

A palladium-catalyzed asymmetric three-component synthesis of α-arylglycine derivatives starting from glyoxylic acid, sulfonamides and arylboronic acids is reported. This novel, operationally simple method offers access to the α-arylglycine scaffold in good yields and enantioselectivities. The utilization of a tailored catalyst system enables the enantioselective synthesis of the desired αarylglycines despite a fast racemic background reaction. The obtained products can be directly employed as building blocks in peptide synthesis.

A palladium-catalyzed asymmetric three-component synthesis of α-arylglycine derivatives starting from glyoxylic acid, sulfonamides and arylboronic acids is reported. This novel, operationally simple method offers access to the α-arylglycine scaffold in good yields and enantioselectivities. The utilization of α tailored catalyst system enables the enantioselective synthesis of the desired α-arylglycines despite a fast racemic background reaction. The obtained products can be directly employed as building blocks in peptide synthesis.

A Brønsted acid is shown to catalyse the inter-metal exchange of mono-anionic (alkoxide and amide) and dianionic (imido) ligands in four-coordinate molybdenum complexes of the type Mo(NR) 2 (X) 2 (R ‫؍‬ alkyl, aryl; X ‫؍‬ alkoxide, amide). Scheme 1 The inter-metal exchange of multiply-bonded oxo and imido ligands via oxo and imido bridges. COMMUNICATION 3242

Experimental and computational studies in the synthesis of 2-amino-4,6-diphenylnicotinonitrile using HBF 4 as an oxidizing promoter catalyst under mild and solvent free conditions were carried out. The suggested anomeric based oxidation (ABO) mechanism is supported by experimental and theoretical evidence. The theoretical study shows that the intermediate isomers with 5R-and 5S-chiral positions have suitable structures for the aromatization through an anomeric based oxidation in the final step of the mechanistic pathway.

Evidence gathered both from X-ray diffraction data and from molecular modelling studies suggests that the introduction of a gem-dimethyl moiety at C1 in 2-amino-2-ferrocenylethanol should exert strong conformational control on the ferrocenyl group when this compound is incorporated into a heterocyclic ring. In order to test this hypothesis, we have developed an efficient, enantioselective and enantiodivergent route to 1-amino-1-ferrocenyl-2-methylpropan-2-ol. According to our expectations, the corresponding 1,3-oxazolidin-2-one (Fc-ÔSuperQuatÕ) exhibited excellent diastereofacial selectivity in the Diels-Alder reaction of its N-crotonyl derivative with cyclopentadiene, in sharp contrast to the lack of diastereoselectivity observed when using the unsubstituted 4-ferrocenyl-1,3-oxazolidin-2-one. In a similar way, the presence of a gem-dimethyl group at C5 in a 2-(2-diphenylphosphinophenyl)-4-ferrocenyl-1,3-oxazoline (Fc-PHOX) ligand brings about a major change in the enantioselectivity of the palladium-catalyzed asymmetric allylic substitution by dimethyl malonate anion, and leads to unprecedented (for PHOX ligands derived from acyclic 2-amino alcohols) levels of asymmetric induction in substrates such as (E)-1,3-dimethyl-2-propenyl and 2-cyclohexenyl acetates.

A chiral Manganese (III) salen complex was immobilized on the walls of MCM-41 (mobile crystalline material) through the multi-grafting method. The immobilized complex was characterized by XRD, FTIR, UV-Vis, ICP and Nitrogen sorption, and was applied to the asymmetric epoxidation of unfuctionalized alkenes including 1,2-dihydronaphthalene, α-methylstyrene, cis-β-methylstyrene, styrene using NaClO and m-chloroperbenzoic acid (m-CPBA) as oxidants respectively. The immobilized complex showed good activity and enantioselectivity in the epoxidation of 1,2-dihydronaphthalene by using NaClO as oxidant. It could also be run for 4 times in the epoxidation of α-methylstyrene without obvious loss of activity or enantiomeric excess.

Three new homochiral bis-diamine-bridged bi-Mn(salen) complexes were synthesized. Their catalysis on asymmetric epoxidation of α-methylstyrene, styrene and indene was studied with NaClO and m-CPBA as oxidants respectively. This homogeneous catalyst exhibited comparable catalytic activity and enantioselectivity to the Jacobsen's catalyst in the asymmetric epoxidation of unfunctionalized olefins. Furthermore, the catalyst could be conveniently recovered and reused at least five times without significant losses of both activity and enantioselectivity. Specially, it also could be efficiently used in large-scale reactions with superior catalytic disposition being maintained at the same level, which provided the potential for the applications in industry. The effect of axial bases, temperature and solvent on activity and enantioselectivity of the catalytic system were also studied. homochiral bi-Mn(salen) complex, enantioselective, asymmetric epoxidation, unfunctionalized olefins

Three new chiral salen-Mn(III) complexes with sugars at the C-5(5 0 ) positions of the salicylaldehyde moieties of the salen ligand were synthesized. Their structures were characterized by FTIR, MS, and elemental analysis. The complexes together with two previously reported ones were successfully used as chiral catalysts for the oxidative kinetic resolution (OKR) of 1-phenylethanol using PhI(OAc) 2 as an oxidant and KBr as an additive. Excellent enantiomeric excess (up to 89%) of the product was achieved in 0.5 h at 20 °C. The results showed that the sugars at C-5(5 0 ) of salicylaldehyde moieties in the ligand had influences on the catalytic performances of the complexes. It was concluded that the sugars with the same rotation direction of polarized light as the diimine bridge within the complex could enhance the chiral induction of the complex in the OKR of 1-phenylethanol, but the sugars with the opposite one would reduce that of the corresponding complex.

Bis-(1H-pyrazol-1-yl)alkanes were deprotonated at the pyrazole 5-positions on treatment with LDA in THF at low temperature. These dianions reacted with tert-butylisocyanate as the electrophile to install a tert-butylamide group at the pyrazole 5-position. The obtained amides were next converted into the respective diboronic acids by Br-Li exchange with t-BuLi in THF at low temperature, followed by the use of triethyl borate as the electrophile. The X-ray analysis of the obtained diboronic acids revealed the presence of a variety of structural motifs, which stabilize the structure by hydrogen bond formation. The stabilization pattern differs greatly with a minor modification of the linker connecting the pyrazole rings.

Treatment of 1,3-diphosphinopropane with acetylacetone in the presence of HCl gives the new chiral bis(phosphaadamantyl)propane ligand (bpap) (1) as a mixture of diastereoisomers. Recrystallization from ethanol gives a mixture enriched in rac diastereoisomer (90% rac/10% meso). The enriched mixture reacts with [RuHCl(PPh 3 ) 3 ] in refluxing THF to give [RuHCl(bpap)(PPh 3 )] (2) in 73% yield. Compound 2 reacts readily with chiral diamines giving octahedral trans-[RuHCl(bpap)(diamine)] complexes 3 (diamine = (1R,2R)-1,2-diaminocyclohexane) and 4 (diamine = (1R,2R)-1,2-diphenylethylenediamine). Compounds 3 and 4 are very active catalysts for H 2hydrogenation of neat acetophenone in the presence of KO t Bu as a strong base under mild conditions (room temperature, 3 atm of H 2 ). The low ee values for 1-phenethanol can be attributed to the similar shapes of two terminal adamantoid cages and the flexible backbone of the bpap ligand. The structures of complexes 2 and 3 have been determined by single-crystal X-ray diffraction.

An extremely mild protocol that employs readily available starting materials, i.e., aldehyde, amine and alkyl diazoacetate, returns structurally diverse N‐substituted‐C‐2/3‐difunctionalised aziridines in excellent yields and stereoselectivities when pyridinium triflate is incorporated as an organocatalyst. The reaction process is environmentally benign affording water and nitrogen as the only by‐products. This racemic protocol paves the way for the development of novel asymmetric organocatalysts capable of generating optically active aziridines.

A series of new bidentate N,S-ligands—aziridines containing a para-substituted phenyl sulfide group—was synthesized and evaluated in the Pd-catalyzed Tsuji–Trost reaction and addition of diethylzinc and phenylethynylzinc to benzaldehyde. A high enantiomeric ratio for the addition reactions (up to 94.2:5.8) was obtained using the aziridine ligand bearing a p-nitro phenyl sulfide group. Collected results reveal a specific electronic effect that, by the presence of particular electron-donating or electron-withdrawing groups in the PhS- moiety, influences the σ-donor–metal binding and the enantioselectivity of the catalyzed reactions.

The genus Psychotria is well known as a source of alkaloids and has contributed several novel indole-type alkaloids with quite a broad spectrum of bioactivities. This study was focused on identifying the alkaloids from the leaves of P. malayana Jack from Lombok island on the basis of Gas Chromatography-Mass Spectroscopy (GC-MS) data and the sample preparation followed acid-base extraction. The study showed that the major alkaloid contained by the leaves was hodgkinsine and other minor compounds, namely calycanthine, chimonantine, 2-ethyl-6-methylpyrazine, and 3-methyl-1,2,3,4-tetrahydrogamma-carboline. Bioactivities of the compounds were also discussed.

Ethyl propiolate undergoes one-pot three-step thioconjugate addition-oxidation-Diels-Alder cycloaddition when treated with a variety of thiols in the presence of catalytic base, meta-chloroperbenzoic acid, lithium perchlorate, and cyclopentadiene. The reaction of S-aryl thiols is catalyzed by trialkylamines, and the reaction of aliphatic thiols requires catalytic alkoxide base. Yields of the major diastereomer of the conveniently functionalized bicyclic products range from 47 to 81% depending upon the thiol reactant, which compares favorably to yields observed when the entire synthesis is performed step by step.

Enantiopure 10-(4-methylpiperazin-1-yl)isoborneol, a N/N/O-tridentate chiral diamino isoborneol, has been obtained from enantiopure ketopinic acid and its catalytic activity (as chiral ligand in the enantioselective addition of diethylzinc to benzaldehyde) measured and compared with the previously reported data for related N/N/O, N/O/O, and N/O isoborneols. It is demonstrated that the pentacoordinated-zinc Oppolzer's model for transition states is useful for explaining the catalytic behavior of N/N/O-tridentate ligands. In such cases, stable syn-or anti-type transition states can be proposed depending on the catalyst's conformational flexibility.

Enantiopure norbornane-based c-amino alcohols 1-4 have been obtained from (+)-camphor and their catalytic behaviour as chiral ligands for the enantioselective addition of diethylzinc to benzaldehyde compared to these described for homologous b-and damino alcohols. This has allowed the first study on the influence of the size of the catalytic zinc-chelate ring on the catalytic activity, which results in the unexpected observance of a non-linear correlation between enantioselectivity and chelate ring size (conformational flexibility). An empirical rationalisation of the observed phenomenon was realised on the basis of consideration of the energeticallyfavoured Noyori-type transition states.

The use of Rh catalysts derived from a phospholanephosphite ligand were found to be more productive than the classic rhodium/BINAP system in enantioselective conjugate additions. These catalysts enable the use of lower amounts of aryl boronic acid in an asymmetric arylation reaction that required [a] Dr.

Developing more efficient catalysts remains one of the primary targets of organometallic chemists. To accelerate reaching this goal, effective molecular descriptors and visualization tools can represent a remarkable aid. Here, we present a Web application for analyzing the catalytic pocket of metal complexes using topographic steric maps as a general and unbiased descriptor that is suitable for every class of catalysts. To show the broad applicability of our approach, we first compared the steric map of a series of transition metal complexes presenting popular mono-, di-, and tetracoordinated ligands and three classic zirconocenes. This comparative analysis highlighted similarities and differences between totally unrelated ligands. Then, we focused on a recently developed Fe(II) catalyst that is active in the asymmetric transfer hydrogenation of ketones and imines. Finally, we expand the scope of these tools to rationalize the inversion of enantioselectivity in enzymatic catalysis, achieved by point mutation of three amino acids of mononuclear p-hydroxymandelate synthase.

The aim of this Bachelor thesis was to synthesise a ligand of the pinene-pyrimidine type. Following the literature procedure, α-pinene (racemate) was chosen as starting material and four synthetic steps out of five have been optimised (see Fig. 2) In the first step the formation in situ of the reactant, NOCl, has been tested but the product, the nitrosochloro-derivate, was obtained with a lower yield (20%) compared to the procedure in which exogenous NOCl is bubbled through the reaction mixture (36%). Optimisation of the step 2 (formation of the pinocarvone oxime) was then performed in which various amines and bases were tested, and the highest yield obtained was 39%. The formation of the isoxazole (step 3) worked well and only the purification by distillation caused a decrease of yield to 48% because of the presence of iodine impurities and the small quantity of product to distil. Step 4 (formation of the enamine aldehyde by hydrogenation) was straightforward (yield 99%). Introduct...

magnified imageFour new chiral polymers of BINOL‐Salen‐cobalt(III) salt complexes have been designed, synthesized and applied to the direct fabrication of chiral propylene carbonate from racemic propylene oxide. The (R/S)‐polymer catalyst 2 and (S/R)‐polymer catalyst 4 exhibit better enantioselectivity than the (R/R)‐polymer catalyst 1 and the (S/S)‐polymer catalyst 3 and have been recovered and reused more than ten times without loss of activity and enantioselectivity.

Im Jahr 1988 wurde zum ersten Mal ein Gadolinium-Komplex als Kontrastmittel für die Magnetresonanzbildgebung (MRI) zugelassen. Seitdem werden Gd(III)-Komplexe jährlich bei Millionen von Scans weltweit in Kliniken zur Verbesserung des Bildkontrasts verabreicht. [1, 2] Es ist davon auszugehen, dass durch die Entwicklung von immer empfindlicheren und spezifischeren Kontrastmitteln ihr Einsatz und somit ihre Bedeutung weiter zunehmen werden. Im Vergleich zu anderen bildgebenden Diagnostikverfahren, wie beispielsweise der Röntgendiagnostik, [3, 4] der Sonografie, [5] der Computertomographie (CT) oder der Positronenemissionstomographie (PET), [3, 6] besitzt die MRI eine herausragende dreidimensionale Bildauflösung verbunden mit der Fähigkeit, zwischen verschiedenen Weichteilgeweben differenzieren zu können. [2, 8] Darüber hinaus handelt es sich um eine nicht-invasive Technik, die auch keinen Einsatz ionisierender Strahlung erfordert. Trotz der schon bestehenden Vorteile richtet sich das Interesse der Forschung auf eine weitere Verbesserung der Ortsauflösung, eine Verkürzung der Messzeit und die weitere Optimierung der Kontrastmittel für spezifische Aufgaben. In der Medizin werden Kontrastmittel beispielsweise eingesetzt um Leberschäden, Störungen der Blut-Hirn-Schranke, das Auftreten von Anomalien in der Ausscheidung über die Nieren oder Probleme im Blutkreislauf feststellen zu können. Weitere Anwendungsgebiete sind die Angiographie und die Früherkennung von Tumoren. Die Kontrastmittel selbst sind bei der Bildgebung nicht direkt sichtbar, lediglich ihre Wirkung kann beobachtet werden. Sie beruht darauf, dass die longitudinale (T 1 ) und/oder die transversale (T 2 ) Relaxationszeit der Wasserprotonen im zu untersuchenden Gewebe durch die Kontrastmittel verkürzt werden. Die erhöhte longitudinale Relaxation führt zu einem intensiveren Signal in kürzerer Zeit und einer Verbesserung des Signal-Rausch-Verhältnisses, wodurch ein schärferes Bild erhalten werden kann. Eine verstärkte transversale Relaxation schwächt das Signal dagegen ab, so dass das betreffende Gewebe dunkel dargestellt wird. Prinzipiell kann man zwei Arten von Kontrastmitteln unterscheiden: superparamagnetische und paramagnetische. Die superparamagnetischen Eisenoxid-Nanopartikel, wie SPIOs (superparamagnetic iron oxides), USPIOs (ultrasmall superparamagnetic iron oxides) und CLIOs (cross-linked iron oxides), bewirken eine 1. Einleitung__________________________________________________________ Verkürzung der T 2 -und vor allem der T 2 * -Zeit, wohingegen Kontrastmittel mit paramagnetischen Metallzentren, wie Gd(III), Mn(II) oder Fe(III), hauptsächlich die T 1 -Zeit verringern. Darüber hinaus ist seit Beginn dieses Jahrhunderts eine neue Klasse der MRI-Kontrastmittel, sogenannte CEST (chemical exchange saturation transfer) -Reagenzien, Gegenstand zahlreicher Forschungsarbeiten. Die CEST-Reagenzien besitzen mindestens einen austauschbaren Protonenpool, der durch Bestrahlung bei ihrer Absorptionsfrequenz gesättigte Magnetisierung auf das Signal der Wassermoleküle aus der Umgebung überträgt. Dadurch erzeugen diese Reagenzien einen Frequenz-codierten Kontrast, wodurch sich durch Auswahl der passenden Sättigungsfrequenz der austauschenden Protonen mehrere Kontrastmittel im selben Bild detektieren lassen. Ein weiterer Vorteil der CEST-Reagenzien ist, dass kein Kontrollscan vor Kontrastmittelgabe benötigt wird. Um den weiter wachsenden Anforderungen zu genügen, bedarf es daher einer Weiterentwicklung bestehender beziehungsweise der Synthese neuer Kontrastmittel. Ziel besteht nun darin, neue, zielorientierte Kontrastmittel zu entwickeln, die beispielsweise an Biomoleküle, Proteine, Vitamine oder Antikörper gekoppelt werden können und sich so spezifisch an der zu untersuchenden Stelle im Körper anreichern. Darüber hinaus sollen diese Kontrastmittel den Bildkontrast erhöhen, wodurch sich die für die Diagnostik benötigte Kontrastmittelkonzentration herabsenken ließe. [23, 24] Des Weiteren wird die sogenannte molekulare Bildgebung immer wichtiger werden, die dazu beitragen soll, biologische Abläufe besser zu verstehen, Krankheiten bereits frühzeitig am Beginn ihres Entstehens zu diagnostizieren sowie die therapeutischen Maßnahmen zu überwachen. Dabei wird auch die Entwicklung Frequenz-codierter Kontrastmittel eine große Rolle spielen, die die gleichzeitige Detektion verschiedener Kontrastmittel im selben Bild bei der MRT ermöglichen soll, gerade in Hinblick auf den zukünftigen klinischen Einsatz weiterentwickelter, leistungsfähigerer Kernspintomographen. [25] 2. Kenntnisstand 2.1 Allgemeine Anforderungen an Kontrastmittel für die Magnetresonanzbildgebung Das paramagnetische Gd 3+ -Ion besitzt sieben ungepaarte Elektronen und einen symmetrischen 8 S Grundzustand, was zu einem hohem magnetischen Moment mit einer langen Elektronenspin-Relaxationszeit führt. Diese beiden Eigenschaften bewirken eine starke diploare Wechselwirkung mit den Protonen der Wassermoleküle im umliegenden Gewebe. Das Gd 3+ -Ion hat in Säugetieren keine natürliche physiologische Funktion, aber freie Gd 3+ -Ionen sind im Körper schon in geringen Dosen (10 -20 µmol/kg) extrem giftig [2, 13] und stehen im Verdacht, die nephrogene systemische Fibrose (NSF), früher als nephrogene fibrosierende Dermopathie (NFD) bezeichnet, möglicherweise (mit)auszulösen. Bei der NSF handelt es sich um eine im Jahr 2000 erstmals beschriebene, krankhafte Vermehrung des Bindegewebes der Haut, Muskulatur und der inneren Organe, wie Leber, Herz, Lungen und Zwerchfell. [26, 27] Allerdings ist die weltweite Anzahl der erst seit 1997 berichteten Krankheitsfälle sehr gering. Zudem wurde die Erkrankung ausschließlich bei Patienten beobachtet, die bereits eine schwere Nieren-oder Lebervorerkrankung aufwiesen. Anfang des Jahres 2006 wurde erstmals über einen möglichen Zusammenhang von NSF und dem Gd(III)-haltigen Kontrastmittel Omniscan ® , in Einzelfällen auch im Verbindung mit der Gabe von Magnevist ® und OptiMARK ® (nicht in der EU zugelassen), berichtet. [28-32] Deshalb müssen die als Kontrastmittel in der klinischen Diagnostik eingesetzten Gd(III)-Komplexe bestimmte Anforderungen erfüllen: Sie müssen eine hohe thermodynamische, und wenn möglich, auch eine hohe kinetische Stabilität aufweisen, um die Freisetzung sowohl giftiger freier Gd 3+ -Ionen als auch freier Ligandmoleküle im Körper auszuschließen. Darüber hinaus müssen die Gd(III)-Komplexe gegenüber einer Transmetallierung endogener Kationen wie Zn 2+ , Cu 2+ , Fe 3+ und vor allem in Hinblick auf das in hohen Konzentrationen vorliegende Ca 2+ -Ion stabil sein. Aufgrund der nahezu identischen Ionenradien von Gd 3+ und Ca 2+ könnten sonst toxische Gd 3+ -Ionen in die Knochen und die Leber eingebaut werden. Als Calciumantagonist kann freies Gd 3+ im Körper Zugang für Wassermoleküle aus dem Lösungsmittel zum paramagnetischen Metallzentrum nicht eingeschränkt wird (Abbildung 2.4). Abbildung 2.4: Schematische Darstellung eines Mizellen-bildenden Gd-DOTA-Derivats (X, links) sowie seiner Mizellenstruktur in wässriger Lösung (rechts). Die Köpfe der in Abbildung 2.4 gezeigten Mizelle sind allerdings noch relativ flexibel verglichen mit der gesamten Bewegung des Aggregats, so dass der Gewinn an Relaxivität nicht so hoch ist wie erwartet. Die Starrheit der Mizelle kann beispielsweise durch den Einbau von Cholesterin erhöht werden. Ein großer Vorteil dieses Systems ist, dass die Protonenrelaxivitäten im Frequenzbereich von 20 -60 MHz, der für die biomedizinische Anwendung wichtig ist, fast konstant sind. Diese Konstanz ist die Folge eines günstigen Zusammenspiels von Rotationskorrelationszeit und Wasseraustauschgeschwindigkeit. [54] Viele andere makromolekulare Chelate weisen dagegen um 20 MHz ein scharfes Relaxivitätsmaximum auf, mit zunehmender Frequenz sinkt die Relaxivität dann deutlich ab. In neuerer Zeit werden zunehmend sogenannte gemischte Mizellen entwickelt. [57] Die Grundidee basiert darauf, ein neues Kontrastmittel herzustellen, das aus zwei unterschiedlichen Monomeren besteht, von denen eines ein bioaktives Molekül enthält, das fähig ist, die Aggregate an das spezifische biologische Ziel zu bringen. Das andere Monomer besitzt eine Chelateinheit, die mit dem gewünschten Metall, hier Gd(III), stabile Komplexe bilden kann. Beide Einzelbausteine verfügen außerdem über einen lipophilen Schwanz, so dass sie sich miteinander zu einer gemischten Mizelle versammeln können. Die hydrophoben Ketten ermöglichen den Monomeren 2. Kenntnisstand______________________________________________________ 10 Mizellen zu bilden, während die hydrophilen Köpfe auf der Oberfläche der Aggregate für entsprechende Aufgaben zur Verfügung stehen (Abbildung 2.5). [24] Abbildung 2.5: Schematische Darstellung einer gemischten Mizellenstruktur, die in wässriger Lösung von den beiden Monomeren gebildet wird. Auf diese Weise kann ein supermolekulares Aggregat hergestellt werden, das ein bioaktives Molekül enthält und in der Lage ist, eine große Anzahl paramagnetischer Gd 3+ -Ionen an eine spezifische Stelle, in diesem Fall Tumorgewebe, zu transportieren. [24] Ein Nachteil bei der Bildung von Mizellen besteht jedoch darin, dass die paramagnetischen Zentren sich zu nahe beieinander befinden. Die Wechselwirkung zwischen sich nahe kommenden paramagnetischen Zentren erhöht die transversale elektronische Relaxation der Elektronenspins des Gd(III) und kann dadurch die Protonenrelaxivität des Wassers verringern. Dieser Effekt kann vor allem beim MRT-Feld für langsam rotierende Makromoleküle mit hohen Wasseraustauschgeschwindigkeiten nachteilig sein und würde das Erreichen optimaler Relaxivitäten verhindern. Dieser Nachteil kann umgangen werden, indem ein Teil der Gd 3+ -Ionen durch diamagnetische Y 3+ -Ionen ersetzt, und somit der mittlere Abstand zwischen benachbarten Gd 3+ -Ionen vergrößert wird. Aufgrund der ähnlichen Ionenradien von Gd 3+ und Y 3+ (1.053 Å bzw. 1.019 Å) beeinflusst dieser Austausch weder die...

A simple change in the polarity of the solvent allows both enantiomers of substituted succinimides to be obtained in the enantioselective conjugate addition reaction of aldehydes, mainly α,α‐disubstituted, to maleimides catalysed by chiral carbamate‐monoprotected trans‐cyclohexane‐1,2‐diamines. Using a single enantiomer of the organocatalyst, both enantiomers of the resulting Michael adducts are obtained in high yields by simply changing the reaction solvent from aqueous DMF (up to 84 % ee) to chloroform (up to 86 % ee). Theoretical calculations are used to explain this uncommon reversal of the enantioselectivity; two transition state orientations of different polarities are differently favoured in polar or nonpolar solvents.

Aldehydes constitute a main class of organic compounds widely applied in synthesis. As such, catalyst-controlled enantioselective α-functionalization of aldehydes has attracted great interest over the years. In this context, α-branched aldehydes are especially challenging substrates because of reactivity and selectivity issues. Firstly, the transient trisubstituted enamines and enolates resulting upon treatment with an aminocatalyst or a base, respectively, would exhibit attenuated reactivity; secondly, mixtures of E- and Z-configured enamines/enolates may be formed; and third, effective face-discrimination on such trisubstituted sp2 carbon intermediates by the incoming electrophilic reagent is not trivial. Despite these issues, in the last 15 years, several catalytic approaches for the α-functionalization of prostereogenic α-branched aldehydes that proceed in useful yields and diastereo- and enantioselectivity have been uncovered. Developments include both organocatalytic and metal...

Baeyer–Villiger oxidation of racemic bicyclic cyclobutanones with Zr[bis(salicylidene)ethylenediaminato] (salen) complex 1 as catalyst in the presence of a urea-hydrogen peroxide adduct was found to proceed enantiospecifically. The enantiotopos selection in the oxidation was governed primarily by the Zr(salen) catalyst, although migratory aptitude (methine > methylene > methyl) in Baeyer–Villiger oxidation affected the selection to a varied extent, depending on the substrate structures; one enantiomer of cyclobutanones gave exclusively a normal lactone expected from the migratory aptitude, and the other enantiomer gave an abnormal lactone preferentially, the formation of which is counter to the migratory aptitude. Furthermore, the rates of abnormal lactone formation were found to be faster than those of normal lactone formation in most of the oxidations examined. For example, the enantiomer of racemic bicyclo[3.2.0]heptan-6-one giving an abnormal lactone reacted 2.2 times fast...

α-Arylation of N-Boc Pyrrolidine AK 8. Synthesis of Natural Products from (-)-Cytisine AK 8.1. Synthesis of (+)-Hupeol AK 8.2. Synthesis of (+)-Kuraramine AL 8.3. Synthesis of (-)-Tsukushinamines AL 8.4. Synthesis of (-)-Camoensine AL 9. Synthesis of Cytisine-Inspired Compounds AM 9.1. Hydroxynorcytisine AM 9.2. Pyridine Analogues of (-)-Cytisine AM 9.3. Carbon Analogues of (-)-Cytisine AO 9.3.1. Construction of Ring C of Benzazocine Skeleton I AO 9.3.2. Construction of Ring B of Benzazocine Skeleton I AQ 9.4. (±)-Cyfusine AX 9.5. Varenicline and 1,5-Methano-3-benzazepines AX 9.5.1. Construction of Ring C of 1,5-Methano-3-benzazepines AX 9.5.2. 1,5-Methano-benzazepines Substituted on the Aromatic Ring AY 9.5.3. Affinities of 1,5-Methanobenzazepines at nAChRs AZ 10. N-Substituted Cytisine Derivatives AZ 10.1. Natural Products AZ 10.1.1. N-Methylcytisine BA 10.1

The development of a novel asymmetric ring opening of bi-and polycyclic hydrazines with aryl organometallic reagents is presented. The application of this reaction to the most simple bicyclic hydrazine 1a gives a straightforward regio-and diastereoselective access to synthetically useful trans 3,4-disubstituted hydrazinocyclopentenes in an enantioenriched form.