Rh(III)-catalyzed annulations based on C-H activation. Sustainable synthesis of carbo- and heterocycles

One of the main challenges still present within organic synthesis is the ability to achieve complex molecules with high efficiency. In this context metal-catalyzed C-H functionalization processes have gained a lot of attraction due to their ability to increase molecular complexity in few steps and with a minimum generation of waste. These kind of reactions occurs through a metallacyclic intermediate which can be trapped with a huge variety of unsaturated products by a cycloaddition step. This combination of C-H activation and cycloaddition allows to obtain cyclic structures in few steps and high yields. The work realized within my PhD period embraces the field of C-H activation through the development of novel reactivity patterns in Rhodium (III)-catalyzed oxidative annulation reactions. These processes allow to obtain interseting biological and/or biomedic compounds with a high atom and step economy from simple comercial precursors

Exporting homogeneous transition metal catalysts to biological habitats

Transition-metal catalyzed reactions are being increasingly used in biological contexts and even in living cells and organisms. Most of the processes so far developed rely on the ability of metal complexes to bind and activate unsaturated systems in a bioorthogonal way. The reactions are often tracked by fluorescence microscopy, by using reaction probes that emit light only after the reactionThis work has received financial support from Spanish grant PID2019-108624RB-I00 and Juan de la Cierva-Incorporación fellowship (IJC2018-036705-I to A.S.), the Consellería de Cultura, Educación e Ordenación Universitaria (ED431C-2021/25 and Centro Singular de Investigación de Galicia accreditation2019-2022, ED431G 2019/03), the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant No. 340055)S

Rhodium-Catalyzed (5+1) Annulations Between 2-Alkenylphenols and Allenes: A Practical Entry to 2,2-Disubstituted 2H-Chromenes

NOTICE: This is the peer reviewed version of the following article: Casanova, N., Seoane, A., Mascarelas, J. L., Gulías, M. (2015), Rhodium-Catalyzed (5+1) Annulations Between 2-Alkenylphenols and Allenes: A Practical Entry to 2,2-Disubstituted 2H-Chromenes. Angew. Chem. Int. Ed., 54: 2374-2377 [doi: 10.1002/anie.201410350]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archiving.Readily available alkenylphenols react with allenes under rhodium catalysis to provide valuable 2,2-disubstituted 2H-chromenes. The whole process, which involves the cleavage of one C-H bond of the alkenyl moiety and the participation of the allene as a one-carbon cycloaddition partner, can be considered a simple, versatile, and atom-economical (5+1) heteroannulation. The reaction tolerates a broad range of substituents both in the alkenylphenol and in the allene, and most probably proceeds through a mechanism involving a rhodium-catalyzed C-C coupling followed by two sequential pericyclic processes.This work was supported by the Spanish MINECO (grant: SAF2013-41943-R), the ERDF, the European Research Council (Advanced Grant No. 340055), and the Xunta de Galicia (grants: GRC2013-041, EM2013/036 and a Parga Pondal contract to M.G.). We also thank the orfeo-cinqa networkS

Straightforward Assembly of Benzoxepines by Means of a Rhodium(III)-Catalyzed C–H Functionalization of o-Vinylphenols

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Biology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: https://pubs.acs.org/doi/10.1021/ja410538wReadily available o-vinylphenols undergo a formal (5 + 2) cycloaddition to alkynes when treated with catalytic amounts of [Cp*RhCl2]2 and Cu(OAc)2. The reaction, which involves the cleavage of the terminal C–H bond of the alkenyl moiety, generates highly valuable benzoxepine skeletons in a practical, versatile, and atom-economical manner. Using carbon monoxide instead of an alkyne as reaction partner leads to coumarin products which formally result from a (5 + 1) cycloadditionWe are thankful for the financial support provided by the Spanish Grants (SAF2010-20822-C02 and CSD2007-00006 Consolider Ingenio 2010), the ERDF and the Xunta de Galicia Grants GRC2010/12, GR2013-041, INCITE09 209084PR and EM2013/036. M.G thanks Xunta de Galicia for a Parga Pondal contractS

Rhodium(III)-catalyzed intramolecular annulations involving amide-directed C–H activations: synthetic scope and mechanistic studies

Alkyne tethered benzamides undergo rhodium(III)-catalyzed intramolecular annulations to give tricyclic isoquinoline derivatives in good yields. DFT calculations suggest that the reaction mechanism involves a migratory insertion of the alkyne into the rhodium–nitrogen bond of the rhodacycle intermediate that results from the initial C–H activation. This contrasts with the pathway proposed for intermolecular cases, which considers an insertion into the rhodium–carbon instead of the rhodium–nitrogen bond. The annulation is also effective with acrylamides; and, while anilides fail to participate in the process, naphthylamides do undergo the intramolecular annulation, albeit the chemoselectivity is different than for the intermolecular reactionsS

Rhodium(III)‐Catalyzed Annulation of 2‐Alkenylanilides with Alkynes via C‐H Activation: a Direct Access to 2‐substituted Indolines

A Rh(III) complex featuring an electron‐deficient η5‐cyclopentadienyl ligand catalyzes an unusual annulation between alkynes and 2‐alkenylanilides, to form synthetically appealing 2‐substituted indolines. Formally, the process can be viewed as an allylic amination with concomitant hydrocarbonation of the alkyne. Mechanistic experiments indicate that this transformation involves a peculiar Rhodium migration with a concomitant 1,5‐H shiftThis work has received financial support from Spanish grants (SAF2016-76689-R and CTQ2016-77047-P), the Xunta de Galicia (ED431C 2017/19, 2015-CP082 and Centro Singular de Investigación de Galicia accreditation 2016-2019, ED431G/09) the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant No. 340055). The orfeo-cinqa network CTQ2016-81797-REDC is also kindly acknowledgedS

Rhodium‐Catalyzed Annulation of ortho‐Alkenyl Anilides with Alkynes: Formation of Unexpected Naphthalene Adducts

This is the peer reviewed version of the following article: Seoane, A., Comanescu,C., Casanova, N., García-Fandiño, R., Diz, X., Mascareñas, J.L., Gulías, M. (2019), Rhodium-catalyzed annulation of ortho-alkenylanilides with alkynes: Formation of unexpected naphthalene adducts. AngewChemIntEd., 58,1700-1717 [doi: 10.1002/anie.201811747]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archivingThis research received financial support through Spanish grants SAF2016‐76689‐R and CTQ2016‐77047‐P, from the Consellería de Cultura, Educación e Ordenación Universitaria (ED431C 2017119‐041, 2015‐CP082 and Centro Singular de Investigación de Galicia accreditation 2016‐2019, ED431G/09), the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant No. 340055). R.G.‐F. thanks the Spanish Government MINECO for a Ramon y Cajal (RYC‐RYC‐2016‐20335) contract. The orfeo‐cinqa network CTQ2016‐81797‐REDC is kindly acknowledged. All calculations were carried out at Centro de Supercomputación de Galicia (CESGA)S

Incidence of cardiovascular events after kidney transplantation and cardiovascular risk scores: study protocol

[Abstract] Background: Cardiovascular disease (CVD) is the major cause of death after renal transplantation. Not only conventional CVD risk factors, but also transplant-specific risk factors can influence the development of CVD in kidney transplant recipients. The main objective of this study will be to determine the incidence of post-transplant CVD after renal transplantation and related factors. A secondary objective will be to examine the ability of standard cardiovascular risk scores (Framingham, REGICOR, SCORE, and DORICA) to predict post-transplantation cardiovascular events in renal transplant recipients, and to develop a new score for predicting the risk of CVD after kidney transplantation. Methods/design: Observational prospective cohort study of all kidney transplant recipients in the A Coruna Hospital (Spain) in the period 1981-2008 (2059 transplants corresponding to 1794 patients). The variables included will be: donor and recipient characteristics, chronic kidney disease-related risk factors, pre-transplant and post-transplant cardiovascular risk factors, routine biochemistry, and immunosuppressive, antihypertensive and lipid-lowering treatment. The events studied in the follow-up will be: patient and graft survival, acute rejection episodes and cardiovascular events (myocardial infarction, invasive coronary artery therapy, cerebral vascular events, new-onset angina, congestive heart failure, rhythm disturbances and peripheral vascular disease). Four cardiovascular risk scores were calculated at the time of transplantation: the Framingham score, the European Systematic Coronary Risk Evaluation (SCORE) equation, and the REGICOR (Registre Gironi del COR (Gerona Heart Registry)), and DORICA (Dyslipidemia, Obesity, and Cardiovascular Risk) functions. The cumulative incidence of cardiovascular events will be analyzed by competing risk survival methods. The clinical relevance of different variables will be calculated using the ARR (Absolute Risk Reduction), RRR (Relative Risk Reduction) and NNT (Number Needed to Treat). The ability of different cardiovascular risk scores to predict cardiovascular events will be analyzed by using the c index and the area under ROC curves. Based on the competing risks analysis, a nomogram to predict the probability of cardiovascular events after kidney transplantation will be developed. Discussion: This study will make it possible to determine the post-transplant incidence of cardiovascular events in a large cohort of renal transplant recipients in Spain, to confirm the relationship between traditional and transplant-specific cardiovascular risk factors and CVD, and to develop a score to predict the risk of CVD in these patients.Instituto de Salud Carlos III; PI070986Xunta de Galicia; PS09/26Insituto de Salud Carlos III; G03/170Instituto de Salud Carlos III; RD06/ 001

Arqueología en la ACEGA 2: el área arqueológica de O Peto (Vedra, A Coruña)

Cadernos de Arqueoloxía e Patrimonio (CAPA)[EN] The archaeological area of O Peto was discovered during the construction of the highway Santiago-Alto de Santo de Domingo. This site shows the existence of archaeological structures near of the galician Iron Age hillforts. In fact O Peto is an artificialized space (where a set of several structures was exhumed) that belongs to a prerroman iron mining complex that suffered several changes in the beginning of Romanization.[ES] El área arqueológica de O Peto se descubrió durante el control arqueológico de la construcción de la Autopista Santiago-Alto de Santo Domingo. Se trata de un ejemplo significativo de la existencia de estructuras anejas en el entorno inmediato del recinto habitacional de los castros de la Edad del Hierro. Constituye un espacio claramente artificializado en el que se superponen estructuras excavadas en la roca, de naturaleza y finalidad diferentes. A este respecto se configura un espacio construido –aparentemente multifuncional- que experimentó sucesivos procesos de ampliación, redefinición, sellado intencionado y abandono entre la Edad del Hierro y Época Romana. La información aportada por la excavación indica que este yacimiento albergó un complejo minerometalúrgico caracterizado tecnológicamente por la utilización de hornos bajos prerromanos sin sangrado de escoria que procesarían el mineral extraído en el propio yacimiento.Proyecto financiado por la Dirección Xeral de Investigación e Desenvolvemento da Consellería de Innovación, Industria e Comercio (Xunta de Galicia) con cargo a la convocatoria Programa de Tecnoloxías para a Innovación- Tecnoloxías da Construcción e da Conservación do Patrimonio do ano 2004. Código de Proxecto: PGIDIT04CCP606003PRPeer reviewe

Arqueología en la ACEGA 2: el área arqueológica de O Peto (Vedra, A Coruña)

Cadernos de Arqueoloxía e Patrimonio (CAPA)[EN] The archaeological area of O Peto was discovered during the construction of the highway Santiago-Alto de Santo de Domingo. This site shows the existence of archaeological structures near of the galician Iron Age hillforts. In fact O Peto is an artificialized space (where a set of several structures was exhumed) that belongs to a prerroman iron mining complex that suffered several changes in the beginning of Romanization.[ES] El área arqueológica de O Peto se descubrió durante el control arqueológico de la construcción de la Autopista Santiago-Alto de Santo Domingo. Se trata de un ejemplo significativo de la existencia de estructuras anejas en el entorno inmediato del recinto habitacional de los castros de la Edad del Hierro. Constituye un espacio claramente artificializado en el que se superponen estructuras excavadas en la roca, de naturaleza y finalidad diferentes. A este respecto se configura un espacio construido –aparentemente multifuncional- que experimentó sucesivos procesos de ampliación, redefinición, sellado intencionado y abandono entre la Edad del Hierro y Época Romana. La información aportada por la excavación indica que este yacimiento albergó un complejo minerometalúrgico caracterizado tecnológicamente por la utilización de hornos bajos prerromanos sin sangrado de escoria que procesarían el mineral extraído en el propio yacimiento.Proyecto financiado por la Dirección Xeral de Investigación e Desenvolvemento da Consellería de Innovación, Industria e Comercio (Xunta de Galicia) con cargo a la convocatoria Programa de Tecnoloxías para a Innovación- Tecnoloxías da Construcción e da Conservación do Patrimonio do ano 2004. Código de Proxecto: PGIDIT04CCP606003PRPeer reviewe