1,721,041 research outputs found
Enamine/dienamine and brønsted acid catalysis: elusive intermediates, reaction mechanisms, and stereoinduction modes based on in situ NMR spectroscopy and computational studies
Full text linkConspectusOver the years, the field of enantioselective organocatalysis has seen unparalleled growth in the development of novel synthetic applications with respect to mechanistic investigations. Reaction optimization appeared to be rather empirical than rational. This offset between synthetic development and mechanistic understanding was and is generally due to the difficulties in detecting reactive intermediates and the inability to experimentally evaluate transition states. Thus, the first key point for mechanistic studies is detecting elusive intermediates and characterizing them in terms of their structure, stability, formation pathways, and kinetic properties. The second key point is evaluating the importance of these intermediates and their properties in the transition state.In the past 7 years, our group has addressed the problems with detecting elusive intermediates in organocatalysis by means of NMR spectroscopy and eventually theoretical calculations. Two main activation modes were extensively investigated: secondary amine catalysis and, very recently, Brønsted acid catalysis. Using these examples, we discuss potential methods to stabilize intermediates via intermolecular interactions; to elucidate their structures, formation pathways and kinetics; to change the kinetics of the reactions; and to address their relevance in transition states. The elusive enamine in proline-catalyzed aldol reactions is used as an example of the stabilization of intermediates via inter- and intramolecular interactions; the determination of kinetics on its formation pathway is discussed. Classical structural characterization of intermediates is described using prolinol and prolinol ether enamines and dienamines. The Z/E dilemma for the second double bond of the dienamines shows how the kinetics of a reaction can be changed to allow for the detection of reaction intermediates. We recently started to investigate substrate-catalyst complexes in the field of Brønsted acid catalysis. These studies on imine/chiral phosphoric acid complexes show that an appropriate combination of highly developed NMR and theoretical methods can provide detailed insights into the complicated structures, exchange kinetics, and H-bonding properties of chiral ion pairs. Furthermore, the merging of these structural investigations and photoisomerization even allowed the active transition state combinations to be determined for the first time on the basis of experimental data only, which is the gold standard in mechanistic investigations and was previously thought to be exclusively the domain of theoretical calculations.Thus, this Account summarizes our recent mechanistic work in the field of organocatalysis and explains the potential methods for addressing the central questions in mechanistic studies: stabilization of intermediates, elucidation of structures and formation pathways, and addressing transition state combinations experimentally
Decrypting transition states by light: photoisomerization as a mechanistic tool in Brønsted acid catalysis
Full text linkDespite the wide applicability of enantioselective Brønsted acid catalysis, experimental insight into transition states is very rare, and most of the mechanistic knowledge is gained by theoretical calculations. Here, we present an alternative approach (decrypting transition state by light = DTS-hν), which enables the decryption of the transition states involved in chiral phosphoric acids catalyzed addition of nucleophiles to imines. Photoisomerization of double bonds is employed as a mechanistic tool. For this class of reactions four pathways (Type I Z, Type I E, Type II Z, Type II E) are possible, leading to different enantiomers depending on the imine configuration (E- or Z-imine) and on the nucleophilic attack site (top or bottom). We demonstrated that the imine double bond can be isomerized by light (365 nm LED) during the reaction leading to a characteristic fingerprint pattern of changes in reaction rate and enantioselectivity. This characteristic fingerprint pattern is directly correlated to the transition states involved in the transformation. Type I Z and Type II Z are demonstrated to be the competing pathways for the asymmetric transfer hydrogenation of ketimines, while in the nucleophilic addition of acetylacetone to N-Boc protected aldimines Type I E and Type II E are active. Accelerations on reaction rate up to 177% were observed for ketimines reduction. Our experimental findings are supported by quantum chemical calculations and noncovalent interaction analysis
Entwicklung eines Donor/Akzeptor-Konzeptes für die asymmetrische Synthese unsymmetrischer Benzoine mit Hilfe ThDP-abhängiger Enzyme
Full text linkDie vorliegende Arbeit beschreibt die Entwicklung eines Konzeptes, mit dem sich unsymmetrische (R)-Benzoine erstmals sehr effizient in einem Syntheseschritt chemoselektiv und in enantiomerenreiner Form erhalten lassen. Die Generierung dieser Verbindungen erfolgt dabei mittels einer durch die ThDP-abhängigen Enzyme Benzaldehyd-lyase (BAL) und Benzoylformiat-decarboxylase H281A (BFD H281A) katalysierten Kreuz-Benzoin-Kondensation. Das erarbeitete Konzept beruht auf der Ausnutzung der elektronischen und sterischen Eigenschaften sowohl der eingesetzten aromatischen Aldehyde als auch der verwendeten Enzyme. Dadurch wird es möglich, dass bei geeigneter Substratkombination und Enzymauswahl ein Aldehyd selektiv als Donor reagiert, während der zweite Aldehyd selektiv als Akzeptor umgesetzt wird. Durch die resultierende asymmetrische Kreuzkupplung wird so chemo- und enantioselektiv ein Produkt erhalten. Zur Etablierung dieses Donor/Akzeptor-Konzeptes wurden verschiedene Screenings durchgeführt, bei welchen im analytischen Maßstab Kombinationen von aromatischen Aldehyden in wässerigem Milieu bei 30°C Enzym-katalysiert umgesetzt wurden. Zum einen konnten mittels dieser Screenings die beiden Enzyme BAL und BFD H281A als Katalysatoren identifiziert werden, welche die selektive Kreuzkupplung zwischen zwei unterschiedlichen aromatischen Aldehyden zu katalysieren vermögen. Des weiteren wurde das Reaktionsverhalten der Aldehyde in Gegenwart unterschiedlicher Reaktionspartner untersucht und darauf aufbauend eine Einteilung in Donoren und Akzeptoren vorgenommen. Zahlreiche unsymmetrische (R)-Benzoine konnten hochselektiv bezüglich Konstitution und Enantiomerenreinheit auch im präparativen Maßstab synthetisiert werden. Reinigung der Rohprodukte durch Umkristallisieren oder Säulenchromatographie lieferte die reinen Substanzen. Durch Röntgen-Kristallstrukturanalyse des Derivates (R)-2-(4-Brom-benzoyloxy)-2-(2-chlor-phenyl)-1-(3,5-dimethoxy-phenyl)-ethanon konnte nachgewiesen werden, dass die enzymatisch generierten Kreuzkupplungsprodukte (R)-konfiguriert sind. Darüber hinaus wurde die CD-Spektroskopie als generelle Methode zur Bestimmung der absoluten Konfiguration sowohl von unsymmetrischen als auch von symmetrischen Benzoinen etabliert. Durch die charakteristische Abfolge von positiven und negativen Cotton-Effekten wird neben der einheitlichen Konfiguration auch eine einheitliche Konformation der Verbindungen nachgewiesen. Ein Zugang zu den (S)-konfigurierten unsymmetrischen Benzoinen konnte durch kinetische Racematspaltung der racemischen Verbindungen mit dem Enzym BAL erhalten werden. Dabei wurde ausgenutzt, dass das Enzym neben der Ligase-Aktivität auch eine Lyase-Aktivität besitzt. Dies ist ein seltenes Beispiel für eine Racematspaltung via C-C-Bindungsspaltung.Development of a donor-acceptor concept for the asymmetric synthesis of unsymmetrical benzoins by the use of ThDP-dependent enzymes This thesis describes the development of a concept which enables the generation of unsymmetrical and enantiopure (R)-benzoins in one efficient chemoselective synthetic step. The synthesis of these compounds is performed by an enzymatic cross-benzoin condensation using the ThDP-dependent enzymes benzaldehyde lyase (BAL) and benzoylformate decarboxylase H281A (BFD H281A). This concept is taking advantage of the electronic and steric properties of both the aromatic aldehydes and the enzymes. Combining an appropriate pair of benzaldehyde derivatives with an appropriate enzyme it becomes possible to convert one aldehyde selectively as a donor while the other one reacts selectively as an acceptor. The resulting asymmetric and chemoselective cross-coupling leads to one single enantiopure product. In order to establish this concept several screenings on an analytical scale were carried out in which various combinations of aldehydes were converted in the presence of different enzymes in aqueous medium at 30°C. By means of these screenings the potential of the two enzymes BAL and BFD H281A to perform the asymmetric cross-coupling of two different aromatic aldehydes was identified. Moreover, the results obtained concerning the behaviour of the tested aldehydes enabled their classification into donors and acceptors. Various unsymmetrical (R)-benzoins could also be synthesised on a preparative scale. Purification of the crude products was carried out by crystallisation or by column chromatography. By crystal-structure analysis of the derivative (R)-2-(4-bromo-benzoyloxy)-2-(2-chloro-phenyl)-1-(3,5-dimethoxy-phenyl)-ethanone it could be proven that the enzymatically synthesised benzoins are (R)-configurated. Additionally, CD-spectroscopy could be established as a general method to determine the absolute configuration of both symmetrical and unsymmetrical benzoins. Not only the absolute configuration but also the conformation of the benzoins can be derived from the characteristic order of positive and negative Cotton effects. Access to the (S)-configurated unsymmetrical benzoins was obtained by kinetic racemic resolution. Here, the fact that BAL shows a lyase activity additionally to its ligase activity is used. This represents a rare example of a racemic resolution via C-C-bond cleavage
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Synthesis and Reactivity of an Iron–Tin Complex with Adjacent Stannylidyne and Ferriostannylene Units
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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