Controlling the Ambiphilic nature of sigma-arylpalladium intermediates in intramolecular cyclization reactions

The reactivity of main group organometallics, such as organolithium compounds (RLi) and Grignard reagents (RMgX), is quite straightforward. In these species the R group usually exhibits nucleophilic reactivity without any possibility of inducing electrophilic character. In contrast, in organopalladium complexes, researchers can switch the reactivity from electrophilic to nucleophilic relatively simply. Although σ-aryl and σ-vinylpalladium complexes are commonly used as electrophiles in C-C bond-forming reactions, recent research has demonstrated that they can also react with carbon-heteroatom multiple bonds in a nucleophilic manner. Nevertheless, researchers have completely ignored the issue of controlling the ambiphilic nature of such species. This Account describes our efforts toward selectively promoting the same starting materials toward either electrophilic α-arylation or nucleophilic addition reactions to different carbonyl groups. We could tune the properties of the σ-arylpalladium intermediates derived from amino-tethered aryl halides and carbonyl compounds to achieve chemoselective transformations. Therefore, chemists can control the ambiphilic nature of such intermediates and, consequently, the competition between the alternative reaction pathways by the adequate selection of the reaction conditions and additives (base, presence/absence of phenol, bidentate phosphines). The nature of the carbonyl group (aldehydes, ketones, esters, and amides) and the length of the tether connecting it to the aniline moiety also play an important role in the outcome of these processes. Our joint computational and experimental efforts to elucidate the reaction mechanism of these palladium-catalyzed transformations suggest that beyond the formation of the four-membered azapalladacycle, two major factors help to control the dual character of the palladium(II) intermediates derived from 2-haloanilines. First, their high nucleophilicity strongly modifies the interaction of the metal center with the carbonyl group. Second, the additive phenol exchanges the iodide ligand to give an arylpalladium(II) phenoxide complex, which has a beneficial effect on the arylation. The formation of this transient intermediate not only stabilizes the arylpalladium moiety, thus preventing the nucleophilic attack at the carbonyl group, but also assists the enolization reaction, which takes place in a more favorable intramolecular manner. The azapalladacycle intermediate is, in the words of J. R. R. Tolkien, "the one ring to bring them all and in the darkness to bind them." With this intermediate, we can easily achieve the synthesis of a variety of heterocyclic systems by selectively promoting electrophilic α-arylation or nucleophilic addition reactions from the same precursors

Biomimicry in climate adaptive building skins: relevance of applying principles and strategies

There is growing interest in scientific literature and in research projects on climate adaptive building skins -CABS-. A large development of this type of building skins is expected, because of the advantages they offer over other skins, such as th e improvement of environmental quality and energy efficiency, the adaptability to c limate and changing uses of buildi ngs, the ability to use low exergy sources, the potential for integrating architectural design principles with energy efficiency, the possibility of driving the research on new technologies a nd a greater efficiency in the use of materials. However, this development is not taking place in practice, since most projects either remain on experimental prototypes or are im plemented in high budget buildings. This paper examines the relevance of applying a bi omimetic approach to the design of CABS, given the adaptive behaviour of both systems. By studying the correlation between the functi onal requirements of adaptive building skins and adaptive strategies that can be found in natural organisms, we address the possible overcoming of some limits they face in their development – from design, technological, economic and social-. The aim is to further the implementation of biomim etic principles and adaptive strategies to enhance adaptive behaviour, take advantage of the evoluti onary knowledge that nature provides, derive applying principles to achieve best architectural solutions, serve as a driver of innovation in architecture and promote efficiency and sustainabilit y in building skins, using principles such as optimality in resource management, resilience behaviour , exchange of information and energy with the environment, complexity by organization of simple elements, or multifunctionality. Finally, biomimicry has shown to be a suitable approach, which, by putting systematic design processes into practice, yet to achieve, could promot e the widespread developm ent of climate adaptive building skins

Galerkin discontinuo local aplicado a problemas de ondas acústicas: condiciones de frontera absorbente locales de bajo orden

En este trabajo se presenta una comparación de la solución numérica de la ecuación de Helmholtz utilizando el método de elementos finitos Galerkin Discontinuo Local (LDG) con varias condiciones de contorno absorbentes locales de bajo orden. Se describe brevemente el proceso de discretización y se realizan pruebas con ejemplos clásicos presentes en la literatura.Peer Reviewe

Contribution of "Omic" studies to the understanding of CADASIL. A systematic review

Altres ajuts: Generación Project, Maestro Project, INVICTUS+ networkAltres ajuts: Fundació la Marató de TV (Epigenesis Project)CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a small vessel disease caused by mutations in NOTCH3 that lead to an odd number of cysteines in the epidermal growth factor (EGF)-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraines, psychiatric disorders, recurrent strokes, and dementia. Omic technologies allow the massive study of different molecules for understanding diseases in a non-biased manner or even for discovering targets and their possible treatments. We analyzed the progress in understanding CADASIL that has been made possible by omics sciences. For this purpose, we included studies that focused on CADASIL and used omics techniques, searching bibliographic resources, such as PubMed. We excluded studies with other phenotypes, such as migraine or leukodystrophies. A total of 18 articles were reviewed. Due to the high prevalence of NOTCH3 mutations considered pathogenic to date in genomic repositories, one can ask whether all of them produce CADASIL, different degrees of the disease, or whether they are just a risk factor for small vessel disease. Besides, proteomics and transcriptomics studies found that the molecules that are significantly altered in CADASIL are mainly related to cell adhesion, the cytoskeleton or extracellular matrix components, misfolding control, autophagia, angiogenesis, or the transforming growth factor β (TGFβ) signaling pathway. The omics studies performed on CADASIL have been useful for understanding the biological mechanisms and could be key factors for finding potential drug targets

La previsión social complementaria, un apoyo necesario para la viabilidad del sistema de pensiones español = Complementary pensions, a necessary suport for the feasibility of Spanish pensions system

Bajo la consideración de los cambios demográficos que se presentan y una óptica de los procesos de reforma de las pensiones públicas que se centran exclusivamente en la sostenibilidad, este trabajo defiende el “sistema de los tres pilares” como un mecanismo factible para garantizar la sostenibilidad, adecuación y suficiencia del sistema español de pensiones. Esto nos lleva al estudio de la previsión social privada, tanto desde el punto de vista empresarial como individual. Finalmente, se propondrán medidas y mecanismos de mejora para que la instauración de la previsión social complementaria sea lo más justa y equitativa posible

A Joint experimental-computational comparative study of the Pd(0)-catalysed reactions of aryl iodides and aldehydes with N, O, and S tethers

The influence of the heteroatom (nitrogen, oxygen, and sulfur) on the course of the palladium‐catalysed intramolecular reactions of aryl iodides and aldehydes having heteroatom‐containing tethers has been explored by an extensive experimental-computational (DFT) study. Two series of substrates were considered, namely aldehydes bearing either the α‐(2‐iodobenzylheteroatom) or β‐(2‐iodophenylheteroatom) moieties. While some experimental differences were observed when changing from nitrogen to oxygen or sulfur in the 2‐iodobenzyl series, the aldehydes in which the heteroatom is directly bonded to the aromatic ring showed common chemical behaviour regardless of the nature of the heteroatom. The different reaction pathways leading to the experimentally observed reaction products were studied by computational means. Our calculations suggest that in all cases the initial nucleophilic addition involving a σ‐aryl-PdII intermediate is preferred over the competing concerted metallation-deprotonation (CMD) process. Keywords: Homogeneous catalysis / Palladium / Cyclization / Heterocycles / Density functional calculation

Evaluando la evaluación. Metaevaluación de un proyecto de cooperación internacional al desarrollo en seguridad alimentaria y fortalecimiento institucional de FAO Nicaragua

Este trabajo versa sobre la metaevaluación del proyecto UA-SAN en el que participe en FAO Nicaragua. Cabe distinguir que no me dispongo a evaluar el proyecto en sí, puesto que fue una de las funciones que desarrollé a nivel técnico durante su desarrollo con el resto del equipo, por tanto quiero realizar la metaevaluación del mismo, puesto que me pregunto en qué medida otro tipo de evaluación podría haber guiado más productivamente al proyecto y atreverme a proponer una metodología de metaevaluación aplicada desde el tímido acercamiento que he tenido a las escasas experiencias de metaevaluación en el ámbito de la cooperación.Departamento de GeografíaMáster en Cooperación Internacional para el Desarroll

Synthesis of isoquinolin-4-ols by palladium-catalysed intramolecular nucleophilic addition of aryl iodides to aldehydes

A palladium‐catalysed intramolecular nucleophilic addition of aryl iodides to aldehydes leading to tetrahydroisoquinolin‐4‐ols is reported. A variety of products were isolated in good to excellent yields. The joint experimental‐computational study shows that although two competitive reaction pathways can be promoted by Pd(0) starting from α‐(2‐iodobenzylamino)‐aldehydes, the selectivity of the process can be controlled by the proper selection of the base. While the nucleophilic addition of the aryl‐Pd(II) intermediate to the carbonyl group is selectively promoted by using the base triethylamine (Et3N), the CH bond activation at the formyl group competes with the nucleophilic addition only when the base is replaced by cesium carbonate (Cs2CO3). Keywords: catalysis; cyclization; density functional theory (DFT) calculations; nucleophilic addition; palladiu

Palladium-catalysed intramolecular carbenoid insertion of α-diazo α-(methoxycarbonyl)acetanilides for oxindole synthesis

A novel, selective palladium-catalysed carbenoid C(aryl)-H insertion of α-diazo-α-(methoxycarbonyl)acetanilides leading to oxindoles is described