Search

Nickel-catalyzed reductive carboxylation reactions of aryl electrophiles typically require the use of metallic reducing agents. At present, the prevailing perception is that these serve as both a source of electrons and as a source of Lewis acids that may aid CO₂ insertion into the Ni–C bond. Herein, we provide evidence for the in situ formation of organometallic species from the metallic reductant, a step that has either been ruled out or has been unexplored in catalytic carboxylation reactions with metal powder reductants. Specifically, we demonstrate that Zn(0) acts as a reductant and that Zn(II) generates arylzinc species that might play a role in the C(sp²)–S carboxylation of arylsulfonium salts. Overall, the reductive Ni-catalyzed C(sp²)–S carboxylation reaction proceeds under mild conditions in a non-amide solvent, displays a wide substrate scope, and can be applied to the formal para C–H carboxylation of arenes.

A Ni-catalyzed reductive carboxylation ofN-substituted aziridines with CO2at atmospheric pressure is disclosed. The protocol is characterized by its mild conditions, experimental ease, and exquisite chemo- and regioselectivity pattern, thus unlocking a new catalytic blueprint to access β-amino acids, important building blocks with considerable potential as peptidomimetics.

A dual catalytic sp3 α C–H arylation and alkylation of benzamides with organic halides is described. This protocol exhibits an exquisite site selectivity, chemoselectivity, and enantioselectivity pattern, offering a complementary reactivity mode to existing sp3 arylation or alkylations via transition metal catalysis or photoredox events.

A redox-neutral intermolecular dicarbofunctionalization of styrenes with CO2 at atmospheric pressure and carbon-centered radicals is described. This mild protocol results in multiple C–C bond-forming reactions from simple precursors in the absence of stoichiometric reductants, thus exploiting a previously unrecognized opportunity that complements existing catalytic carboxylation events.

A switchable site-selective catalytic carboxylation of allylic alcohols has been developed in which CO2 is used with dual roles, both facilitating C–OH cleavage and as C1 source. This protocol is characterized by its mild conditions, absence of stoichiometric organometallic reagents, broad scope and exquisite regiodivergency that can be modulated by the ligand employed.

Catalytic carbon-carbon bond-formation has allowed for the streamline of synthetic routes when assembling complex molecules1. This is particularly important when incorporating saturated hydrocarbons, common motifs in petrochemicals and biologically- relevant molecules. However, cross-coupling methods involving alkyl electrophiles occur at specific and previously functionalised sites2. Herein, we describe the discovery of a catalytic method capable of promoting carboxylation reactions at remote and unfunctionalised aliphatic sites under atmospheric pressure of CO2. The reaction occurs via selective migration of the catalyst along the hydrocarbon side-chain3 and operates with excellent regio- and chemoselectivity profile. Our results demonstrate that site-selectivity can be switched and controlled, allowing for the functionalisation of less-reactive positions in the presence of a priori more reactive ones. Furthermore, we show that raw materials obtained in bulk from petroleum processing, such as alkanes and unrefined mixtures of olefins, can be used as substrates. This constitutes a unique opportunity to integrate a catalytic platform en route to valuable fatty acids by direct transformation of petroleum-derived feedstocks4. We anticipate that our methodology will have a broad impact in the preparation of carboxylic acids from simple chemical feedstocks, and will lead to new knowledge in synthetic design when targeting the controlled functionalisation of saturated hydrocarbon chains.

A Ni-catalyzed reductive carboxylation technique en route to cyclopropyl carboxylic acids has been developed. This user-friendly and mild transformation operates at atmospheric pressure of CO 2 and utilizes either organic halides or alkene precursors, thus representing the first example of catalytic reductive carboxylation of secondary counterparts lacking adjacent p-components. &nbsp

A catalytic carboxylation of unactivated primary, secondary & tertiary alkyl chlorides with CO2 at atmospheric pressure is described. This protocol represents the first intermolecular cross-electrophile coupling of unactivated alkyl chlorides, thus leading to new knowledge in the cross-coupling arena.

A visible-light-mediated atom transfer radical cyclization of unactivated alkyl iodides is described. This protocol operates under mild conditions and exhibits high chemoselectivity profile while avoiding parasitic hydrogen atom transfer pathways. Preliminary mechanistic studies challenge the perception that a canonical photoredox catalytic cycle is being operative.

Metal-catalyzed transformations that forge carbon–heteroatom bonds are of central importance in organic synthesis. Despite the formidable potential of aryl methyl ethers as coupling partners, the scarcity of metal-catalyzed C–heteroatom bond formations via C–OMe cleavage is striking, with isolated precedents requiring specialized, yet expensive, ligands, high temperatures, and π-extended backbones. We report an unprecedented catalytic ipso-silylation of aryl methyl ethers under mild conditions and without recourse to external ligands. The method is distinguished by its wide scope, which includes the use of benzyl methyl ethers, vinyl methyl ethers, and unbiased anisole derivatives, thus representing a significant step forward for designing new C–heteroatom bond formations via C–OMe scission. Applications of this transformation in orthogonal silylation techniques as well as in further derivatizations are also described. Preliminary mechanistic experiments suggest the intermediacy of Ni(0)-ate complexes, leaving some doubt that a canonical catalytic cycle consisting of an initial oxidative addition of the C–OMe bond to Ni(0) species comes into play.

A Pd-catalyzed C(sp3)-H functionalization/carbenoid insertion is described. The method allows for the rapid synthesis of bicyclic frameworks, generating all-carbon quaternary centers via multiple C–C bond-formations in a straightforward manner. &nbsp

In recent years, C–O electrophiles have emerged as powerful alternatives to organic halides, common counterparts in metal-catalyzed cross-coupling reactions. Among their advantages are their low toxicity, ready availability, the natural abundance of phenols, and their pivotal role as synthons in organic synthesis, which makes them particularly attractive vehicles for further functionalization. This review summarizes the most important developments in cross-coupling reactions via catalytic C–O bond activation of particularly unreactive aryl esters, carbamates, and aryl ethers, providing a general overview of the current state of the art and including mechanistic implications as well as future aspects, when appropriate.

We report the first enantioselective CC bond formation through CO bond cleavage using aryl ester counterparts. This method is characterized by its wide substrate scope and results in the formation of quaternary stereogenic centers with high yields and asymmetric induction.

The first catalytic intermolecular proximal C1C2 cleavage of benzocyclobutenones (BCB) without prior carbonyl activation or employing noble metals has been developed. This protocol operates at room temperature and is characterized by an exquisite chemo-, regio- and diastereoselectivity profile, constituting a unique platform for preparing an array of elusive carbocyclic skeletons.

A user-friendly Ni-catalyzed reductive cyclization/carboxylation of unactivated alkyl halides with CO2 is described. The protocol operates under mild conditions with excellent chemoselectivity profile and a divergent syn/anti-selectivity pattern that can be easily modulated by the substrate utilized.

The clinical course after adder bites (Vipera berus) is unpredictable. Antivenom can reduce morbidity markedly. Preventive use of low-molecular-weight heparin is not routinely recommended. We present a case report, where indication for antivenom was not found, and the patient developed pulmonary embolus. Thrombotic complications are known, but to our knowledge pulmonary embolus has not previously been described in the literature.

The low-grade inflammatory state present in obesity contributes to obesity-related metabolic dysregulation, including nonalcoholic steatohepatitis (NASH) and insulin resistance. Intercellular interactions between immune cells or between immune cells and hepatic parenchymal cells contribute to the exacerbation of liver inflammation and steatosis in obesity. The costimulatory molecules, B7.1 and B7.2, are important regulators of cell-cell interactions in several immune processes; however, the role of B7 costimulation in obesity-related liver inflammation is unknown. Here, diet-induced obesity (DIO) studies in mice with genetic inactivation of both B7.1 and B7.2 (double knockout; DKO) revealed aggravated obesity-related metabolic dysregulation, reduced insulin signalling in the liver and adipose tissue (AT), glucose intolerance, and enhanced progression to steatohepatitis resulting from B7.1/B7.2 double deficiency. The metabolic phenotype of B7.1/B7.2 double deficiency upon DIO was accompanied by increased hepatic and AT inflammation, associated with largely reduced numbers of regulatory T cells (Tregs) in these organs. In order to assess the role of B7 costimulation in DIO in a non-Treg-lacking environment, we performed antibody (Ab)-mediated inhibition of B7 molecules in wild-type mice in DIO. Antibody-blockade of both B7.1 and B7.2 improved the metabolic phenotype of DIO mice, which was linked to amelioration of hepatic steatosis and reduced inflammation in liver and AT. Conclusion: Our study demonstrates a dual role of B7 costimulation in the course of obesity-related sequelae, particularly NASH. The genetic inactivation of B7.1/B7.2 deteriorates obesity-related liver steatosis and metabolic dysregulation, likely a result of the intrinsic absence of Tregs in these mice, rendering DKO mice a novel murine model of NASH. In contrast, inhibition of B7 costimulation under conditions where Tregs are present may provide a novel therapeutic approach for obesity-related metabolic dysregulation and, especially, NASH. (Hepatology 2014;60:1196-1210)

A tandem C(sp2)H and C(sp3)H functionalization/CO bond formation catalyzed by iodine(III) reagents generated in situ has been developed. The method shows wide scope under mild conditions and exhibits an unprecedented selectivity profile that can be switched depending on the catalyst employed.

A Ni/Cu-catalyzed silylation of unactivated C–O electrophiles derived from phenols or benzyl alcohols is described. This transformation is characterized by its wide scope and mild conditions, providing a direct access to synthetically versatile silylated compounds. The protocol allows for the coupling of C(sp2)−O and even C(sp3)–O bonds with similar efficiency.

A novel Ni-catalyzed regiodivergent reductive carboxylation of allyl esters with CO2 has been developed. This mild, user-friendly, and operationally simple method is characterized by an exquisite selectivity profile that is dictated by the ligand backbone.

New temporal and spatial discretization methods are developed for multiple scale structural dynamic problems. The concept of fast and slow time scales is introduced for the temporal discretization. The required time step is shown to be dependent only on the slow time scale, and therefore, large time steps can be used for high frequency problems. To satisfy the spatial counterpart of the requirement on time step constraint, finite-spectral elements and finite wave elements are developed. Finite-spectral element methods combine the usual finite elements with the fast convergent spectral functions to obtain a faster convergence rate; whereas, finite wave elements are developed in parallel to the temporal shifting technique. Therefore, the spatial resolution is increased substantially. These methods are especially applicable to structural acoustics and linear space structures. Numerical examples are presented to illustrate the effectiveness of these methods.

Multiple-input multiple-output (MIMO) wireless communication systems have the potential to offer high data rates as well as link reliability. The feasibility of these systems in future mobile communication standards depends on the ability to provide high rates with a reduced amount of channel state information at the transmitter (CSIT), due to limited resource availability on the feedback link. This thesis addresses the problem of optimizing MIMO systems with partial CSIT. On the one hand, we provide methods for obtaining CSIT. On the other hand, we propose techniques to exploit the available sources of CSIT to optimize the system performance. In the first part, point-to-point MIMO channels are considered for the purpose of error rate minimization. Linear precoding techniques are proposed to enhance the performance of space-time coded (STC) MIMO systems, by appropriately combining information on the channel mean and covariance. In the second part of this thesis, we focus on sum-rate performance optimization in MIMO broadcast channels with limited feedback. Low-complexity cross-layer approaches are proposed for systems with joint linear beamforming and multiuser scheduling, optimizing the following parts in the MIMO communications system: linear beamforming techniques, scheduling algorithms, feedback strategies and feedback quantization techniques. A design framework for channel quality information (CQI) feedback design is proposed, based on an estimate on each user's signal-to-interference-plus-noise ratio (SINR). As we show, the system performance can be enhanced by using simple channel quantization strategies combined with optimized linear beamforming techniques., Les systèmes de communication multi-antennaires à l'émission et à la réception (MIMO) sans fil ont le potentiel d'offrir hauts débits et fiabilité. La faisabilité de cette technologie dans des systèmes de communication mobiles dépend de la capacité à offrir des débits élevés avec une quantité réduite de connaissance du canal a l'émetteur (CSIT), car la disponibilité des ressources sur la voie de retour est limitée. Cette thèse traite du problème de l'optimisation des systèmes MIMO avec CSIT partielle. D'une part, nous fournissons des méthodes pour obtenir CSIT. D'autre part, nous proposons des techniques pour exploiter les sources de CSIT afin d'optimiser la performance. Dans la première partie, systèmes MIMO mono-utilisateur sont considérés dans le but de minimiser le taux d'erreur. Techniques de précodage linéaire sont proposées pour améliorer les systèmes MIMO avec codage spatio temporel (STC), en combinant des informations sur la moyenne et la covariance du canal. Dans la deuxième partie, nous nous concentrons sur la maximisation de la somme totale des débits sur la voie descendante des systèmes MIMO multi-utilisateur, avec débit limité sur la voie de retour. Nous proposons des algorithmes inter-couche pour les systèmes avec précodage linéaire et sélection d'utilisateurs, optimisant les parties suivantes: techniques de précodage linéaire, algorithmes de sélection d'utilisateurs, informations à transmettre sur la voie de retour et stratégies de quantification. Au lieu de concevoir des systèmes complexes de feedback, nous montrons que la performance peut être améliorée en utilisant précodage linéaire optimisé et stratégies simples de quantification du canal.

A geometric framework for describing and solving time-dependent implicit differential equations F(t,x,x')=0 is studied, paying special attention to the linearly singular case, where F is affine in the velocities: A(t,x)x' = b(t,x). This framework is based on the jet bundle of a time-dependent configuration space, and is an extension of the geometric framework of the autonomous case. When A is a singular matrix, the solutions can be obtained by means of constraint algorithms, either directly or through an equivalent autonomous system that can be constructed using the vector hull functor of affine spaces. As applications, we consider the jet bundle description of time-dependent lagrangian systems and the Skinner-Rusk formulation of time-dependent mechanics., 20 pages

On-line Survey. (PDF 1971Â kb)

On-line Survey. (PDF 1971Â kb)