Cyclopropanes to spirocycles : a study of Versatile B‒N Motifs

Les dérivés cyclopropanoïques sont des composés importants dans plusieurs domaines tels que la synthèse organique, la chimie médicinale et la science des matériaux. La synthèse asymétrique des dérivés cyclopropanoïques s'est de plus en plus concentrée sur la synthèse stéréocontrolée de cyclopropanes polysubstitutés qui arborent toute une gamme de substituants distincts. Ces méthodes permettent d’accéder à des synthèses divergentes pour préparer des composés pharmaceutiques comportant cette sous-unité. De plus, l'ouverture facile de ce cycle très tendu en fait une bonne cible pour étudier l'activation de la liaison C‒C. C’est pourquoi les cyclopropanes sont parmi les composés les plus attrayants et les plus diversifiés en synthèse organique. La synthèse divergente de dérivés cyclopropanoïques repose sur l'utilisation de précurseurs stables mais réactifs. L'une des réactions pour former des liaisons C‒C les plus couramment utilisées dans la fonctionnalisation à un stade avancé, est la réaction de couplage croisé de Suzuki-Miyaura. C'est l'une des raisons pour lesquelles les borocyclopropanes sont devenus des précurseurs synthétiques attrayants pour la fonctionnalisation et diversification des molécules complexes. L’accès à de telles molécules faciliterait la préparation de molécules cyclopropanoïques de structures diversifiées. Il est difficile de préparer des borocyclopropanes de manière énantiosélective. Dans cette thèse, une cyclopropanation énantiosélective d'acides boroniques protégés dérivés d'alcools allyliques a été réalisée via la réaction de cyclopropanation asymétrique en présence du ligand chiral de type dioxaborolane. Le développement de cette méthodologie a nécessité une modification de la décomplexation oxydative existante du dioxaborolane via son complexe dérivé de la diéthanolamine. Le protocole est maintenant applicable aux dérivés boronates qui incluent des groupements fonctionnels qui sont incompatibles avec les bases. Les borocyclopropanes tétracoordonnés obtenus permettent également la formation de liaisons C‒C et ont démontré une stabilité améliorée par rapport à leurs dérivés tricoordonnés. Une étude plus approfondie sur des complexes cyclopropylméthylamine-boranes (CAB) a démontré que ces derniers pouvaient conduire aux amine-boranes spirocycliques (SCAB). Ces SCAB ont été obtenus grâce à une cascade d'activation des CABs en utilisant le bis(trifluorométhanesulfonimide) (Tf2NH) comme initiateur. L'ouverture du cycle des CAB représente la première conversion des cyclopropanes en spirocycles contenant à la fois un N-spirocentre et un spiro amine-borane. Les amine-boranes ont démontré une activité pharmacologique telle que des propriétés anticancéreuses, anti-inflammatoires et anti-ostéoporotiques. L'incorporation de spirocycles dans un motif augmente le caractère sp3 et la chiralité inhérente. Les SCAB rendent alors des candidats attrayants pour la conception de médicaments. La réaction de SCAB avec de Tf2NH en quantités stoechiométriques a donné un complexe SCAB•NTf2 qui est capable de réduire les fonctions cétone, aldéhyde, imine, nitrobenzène, nitrosobenzène, anthracène, indole et aryl méthyl éther. Le complexe SCAB•NTf2 est également capable de réduire le diphénylacétylène de manière Z-sélective en cis-stilbène. Des études spectroscopiques approfondies ont donné plus d'informations sur la structure de SCAB•NTf2 et nous ont permis de proposer un mécanisme de réduction des groupements fonctionnels ci-dessus. Les études spectroscopiques (RMN, IR et Raman) ont également révélé l'implication d'une liaison α-C‒H au bore dans une liaison hydrogène hypsochromique « improper hydrogen bond » avec [Tf2N]-. L'hyperconjugaison avec l’atome de bore, un acide de Lewis, est proposée, ce qui rend la liaison C‒H acide et donc suffisamment polarisée pour agir comme un donneur de pont hydrogène.Cyclopropane derivatives are incredibly versatile building blocks used in organic synthesis, medicinal chemistry, and materials science. The asymmetric synthesis of cyclopropane derivatives has increasingly focused on achieving polysubstituted cyclopropanes with a range of distinct substituents and their use in divergent syntheses to access pharmaceutical compounds. Moreover, the ring-opening potential of the cyclopropane ring, due to its inherent strain, makes it a facile target for C‒C bond activation and one of the most attractive and diverse cycloalkanes in organic synthesis. Divergent synthesis of cyclopropanes relies on stable pre-installed handles on cyclopropanes that can be activated readily. One of the most common C‒C bond formation approaches used in late-stage functionalization is the Suzuki-Miyaura cross-coupling reaction. As a result, borocyclopropanes have become attractive synthetic building blocks for their use in late-stage functionalization. Methods for the enantioselective synthesis of borocyclopropanes are scarce. In this thesis, the first enantioselective cyclopropanation of an allylic alcohol bearing a tetracoordinate boronate has been achieved via the Charette dioxaborolane-mediated enantioselective cyclopropanation reaction. The development of our method required modification of the existing oxidative decomplexation of dioxaborolane via diethanolamine. The protocol has now been expanded to include boronates and base-sensitive functionalities. The tetracoordinate borocyclopropane obtained was also shown to undergo C‒C bond formation and demonstrated enhanced stability compared to its tricoordinate boronate derivative. Further investigation of boron tethered cyclopropanes led to the discovery of the unique transformation of cyclopropane amine-boranes (CABs) to spirocyclic amine-boranes (SCABs). SCABs were obtained through a cascade activation of CAB via bis(trifluoromethane)sulfonimide (Tf2NH). The ring-opening of CABs represents the first conversion of cyclopropanes to spirocycles containing an N-spirocenter and furthermore an amine-borane spirocore. Amine-boranes have shown pharmacological activity such as anti-cancer, anti-inflammatory, and anti-osteoporotic properties. Incorporating spirocycles into a motif increases sp3 character and inherent chirality, rendering SCABs as attractive candidates for drug design. The reaction of SCAB with stoichiometric amounts of Tf2NH resulted in a SCAB•NTf2 complex that was found to be able to reduce ketone, aldehyde, imine, nitrobenzene, nitrosobenzene, anthracene, and indole functionalities as well as demethylate aryl methyl ethers. The SCAB•NTf2 complex was also capable of reducing diphenylacetylene in a Z-selective manner to cis-stilbene. In-depth spectroscopic studies revealed the structure of SCAB•NTf2 and a mechanism for the reduction of the above functionalities is proposed. The spectroscopic studies (NMR, IR and Raman) revealed the involvement of an α-C‒H bond to boron in improper hydrogen bonding with [Tf2N]-. Hyperconjugation to the Lewis acidic boron is proposed to make the C‒H bond acidic and therefore polarized enough to act as a hydrogen bond donor

Synthesis, magnetism and reactivity of graphene nanoribbons

294 p.En esta tesis profundizaremos se enfoca desde un ángulo fundamental la ciencia de las cintas de grafenoPrimero se definirán sus propiedades basándose en ideas bien fundamentadas como la aromaticidad yla topología. Una vez entrados en materia nos centraremos en los 5-armchair y las 3,1-quirales. Se mues-tra un estudio sobre el crecimiento de los primeros que dio lugar al descubrimiento de un nuevo meca-mismo de polimerización. A continuación se estudian sus propiedades para demostrar cómo los 5-aGNR(por sus siglas en inglés) son materiales topológicos que presentan electrones desapareados con actividadMagnética en sus extremos. Este magnetismo está relacionado con una alta reactividad que también se halló en los 3,1-quirales, a pesar de que estos últimos no presentan magnetismo. Se observó una reactividadextrema frente al agua y el oxígeno. La degradación frente a estos elementos generó radicales magnéticoscon capacidad para acoplarse, lo cual presentó una oportunidad de cuantificar y modelizar este acopla-miento en diferentes configuraciones. Por último, se desarrollaron dos estrategias exitosas a la hora deproteger las cintas del ataque ambiental, las cuales pueden ser extrapoladas a otros derivados del grafenoque muestren la recién descubierta reactividad, lo cual facilitaría su transferencia a la industria

Visible Light-assisted Deconstruction/Refunctionalization of Strained and Unstrained N-Cycloalkylanilines

The exploitation of ring strain as a driving force to facilitate chemical reactions is a well-appreciated principle in organic chemistry. Of the strained carbocycles frequently explored in this respect, cyclopropane ring systems have drawn considerably more interest among synthetic chemists than their homolog, the cyclobutane ring systems, even though the strain energy of cyclobutane (26.7 kcal/mol) is similar to that of cyclopropane (27.5 kcal/mol). We have previously developed a [4+2] annulation reaction for the synthesis of aniline-substituted six-membered carbocycles under photoredox catalysis via the oxidative cleavage of N-cyclobutylanilines. The key reaction involved in this method is a ring-opening process of cyclobutylanilines via single-electron oxidation of the anilines under visible light photoredox conditions to presumably generate distonic radical cation intermediates which possess bimodal reactivity due to the presence of a nucleophilic carbon radical moiety (site Y) and an electrophilic iminium ion moiety (site X) that are spatially separated. We have hitherto successfully achieved orthogonal 1,4-difunctionalization of the two reactive sites by using phenyl allyl sulfone or α-CF3-styrene as radical acceptor to capture the radical at Y and TMSCN as nucleophile to intercept the iminium ion at X respectively. The first of the three works described in this dissertation further exploits isocyanides (or isonitriles)—“stereoelectronic chameleons” that exhibit dichotomous reactivity—as radical acceptors in the difunctionalization of the bimodal amine distonic radical cations to afford both symmetrical and unsymmetrical N-substituted 2,6-diaminopimelonitriles in poor to good yields. This represents the first-ever report of a successful synthetic methodology that exploits the ambivalent reactivities of both distonic radical cations and isocyanides.Again, we report the development of a novel methodology for the synthesis of aminoalkynes from various N-substituted cyclobutane substrates via a sequential visible-light-assisted ring-opening and distal alkynylation with alkynyl hypervalent iodine (III) reagents. An in situ-generated distonic radical cation intermediate possessing resonance-stabilized iminium ion site mediates the transformation of the substrates into various pharmaceutically important nitrogen heterocycles. This methodology constitutes only the second example of aminoalkyne synthesis employing the cycloalkylamine deconstruction/refunctionalization strategy. Finally, we report the first-ever aromatization-promoted, visible-light-assisted deconstructive functionalization of unstrained medium-to-large-sized cycloalkanones using diamines as an activator of the ring cleavage for the synthesis of remotely functionalized quinazolinones. The protocol features an amido radical-mediated C(sp3)-C(sp3) cleavage via an aromatization/radical acceptor-driven ring-opening synergy, without the involvement of transition metals, exogenous oxidants, or chelation assistance. In addition, the reaction exhibits a broad substrate scope, good to excellent product yields, and high regioselectivities

Visible Light-assisted Deconstruction/Refunctionalization of Strained and Unstrained N-Cycloalkylanilines

The exploitation of ring strain as a driving force to facilitate chemical reactions is a well-appreciated principle in organic chemistry. Of the strained carbocycles frequently explored in this respect, cyclopropane ring systems have drawn considerably more interest among synthetic chemists than their homolog, the cyclobutane ring systems, even though the strain energy of cyclobutane (26.7 kcal/mol) is similar to that of cyclopropane (27.5 kcal/mol). We have previously developed a [4+2] annulation reaction for the synthesis of aniline-substituted six-membered carbocycles under photoredox catalysis via the oxidative cleavage of N-cyclobutylanilines. The key reaction involved in this method is a ring-opening process of cyclobutylanilines via single-electron oxidation of the anilines under visible light photoredox conditions to presumably generate distonic radical cation intermediates which possess bimodal reactivity due to the presence of a nucleophilic carbon radical moiety (site Y) and an electrophilic iminium ion moiety (site X) that are spatially separated. We have hitherto successfully achieved orthogonal 1,4-difunctionalization of the two reactive sites by using phenyl allyl sulfone or α-CF3-styrene as radical acceptor to capture the radical at Y and TMSCN as nucleophile to intercept the iminium ion at X respectively. The first of the three works described in this dissertation further exploits isocyanides (or isonitriles)—“stereoelectronic chameleons” that exhibit dichotomous reactivity—as radical acceptors in the difunctionalization of the bimodal amine distonic radical cations to afford both symmetrical and unsymmetrical N-substituted 2,6-diaminopimelonitriles in poor to good yields. This represents the first-ever report of a successful synthetic methodology that exploits the ambivalent reactivities of both distonic radical cations and isocyanides.Again, we report the development of a novel methodology for the synthesis of aminoalkynes from various N-substituted cyclobutane substrates via a sequential visible-light-assisted ring-opening and distal alkynylation with alkynyl hypervalent iodine (III) reagents. An in situ-generated distonic radical cation intermediate possessing resonance-stabilized iminium ion site mediates the transformation of the substrates into various pharmaceutically important nitrogen heterocycles. This methodology constitutes only the second example of aminoalkyne synthesis employing the cycloalkylamine deconstruction/refunctionalization strategy. Finally, we report the first-ever aromatization-promoted, visible-light-assisted deconstructive functionalization of unstrained medium-to-large-sized cycloalkanones using diamines as an activator of the ring cleavage for the synthesis of remotely functionalized quinazolinones. The protocol features an amido radical-mediated C(sp3)-C(sp3) cleavage via an aromatization/radical acceptor-driven ring-opening synergy, without the involvement of transition metals, exogenous oxidants, or chelation assistance. In addition, the reaction exhibits a broad substrate scope, good to excellent product yields, and high regioselectivities

Design of fibers spun from carbon-sphere binary colloidal systems as substrates for cell behaviour control

Applications of carbon nanotubes-based biomaterials in biomedical nanotechnology -- Polylactic-co-glycolic acid (PLGA) -- Poly-Vinyl alcohol -- Carbon nanotubes as macroscopic shape biomaterial and wet spinning process -- Neuronal cells and nerve regeneration -- Objectives and relation with the papers -- Experimental techniques -- Dispersion of carbon nanotubes -- Preparation of aqueous suspension of polylactic-co-glycolic acid (PLGA) -- Preparation of colloid mixture -- Preparation of 5% polyvinyl alcohol (PVA) aqueous solution -- Sinning process -- Characterization of carbon nanotube-based fibres -- In vitro biocompatibility -- Design of fibers spun from carbon nanotube-sphere binary colloidal systems as substrates for cell's behaviour control -- Nanotube-sphere binary colloidal systems (NSBCS0 -- Wet spinning -- Investigation of fibers -- Fibrillar structures supporting the growth of living cells : hybrid integration of SWNTs in macroscopic fibers and their characteristics at the nanoscopic level -- Integration of CNTS fibre characteristics -- In vitro biocompatibility -- Nanoscale surface of carbon nanotube fibers for medical applications : structure and chemistry revealed by TOF-SIMS analysis -- General discussions

Antimonene: a tuneable post-graphene material for advanced applications in optoelectronics, catalysis, energy and biomedicine.

The post-graphene era is undoubtedly marked by two-dimensional (2D) materials such as quasi-van der Waals antimonene. This emerging material has a fascinating structure, exhibits a pronounced chemical reactivity (in contrast to graphene), possesses outstanding electronic properties and has been postulated for a plethora of applications. However, chemistry and physics of antimonene remain in their infancy, but fortunately recent discoveries have shed light on its unmatched allotropy and rich chemical reactivity offering a myriad of unprecedented possibilities in terms of fundamental studies and applications. Indeed, antimonene can be considered as one of the most appealing post-graphene 2D materials reported to date, since its structure, properties and applications can be chemically engineered from the ground up (both using top-down and bottom-up approaches), offering an unprecedented level of control in the realm of 2D materials. In this review, we provide an in-depth analysis of the recent advances in the synthesis, characterization and applications of antimonene. First, we start with a general introduction to antimonene, and then we focus on its general chemistry, physical properties, characterization and synthetic strategies. We then perform a comprehensive study on the allotropy, the phase transition mechanisms, the oxidation behaviour and chemical functionalization. From a technological point of view, we further discuss the applications recently reported for antimonene in the fields of optoelectronics, catalysis, energy storage, cancer therapy and sensing. Finally, important aspects such as new scalable methodologies or the promising perspectives in biomedicine are discussed, pinpointing antimonene as a cutting-edge material of broad interest for researchers working in chemistry, physics, materials science and biomedicine

A theoretical study of CH...X (X=O, N, S, P and Pi) interactions

Ph.DDOCTOR OF PHILOSOPH

Near-Infrared High Efficiency Organic Dye Sensitized Solar Cells (DSCs) and Biological Fluorescent Imaging Dyes

With the energy consumption increase every year, the non-renewable energy sources such as fossil fuels, natural gas, and coal will not sustain forever. In this case, searching for a way to develop a renewable energy source is an emergency. For decades, dye-sensitized solar cells (DSCs) have received intensive attention due to their high power conversion efficiency and low material cost. This dissertation describes efforts to design and synthesize near-infrared organic dyes to apply to two systems: first, for use in the improvement of DSCs by the optimization of electron rich components such as ullazine and cross-conjugated -bridges to increase photon-to-electricity conversion and second, as a way to manipulate the UV-vis absorption and emission of the near-infrared organic dyes to use lower energy photons with wavelength ranges in the therapeutic window (700 nm-1000 nm)

Electron acceptor molecules deposited on epitaxial graphene studied by means of low temperature scanning tunneling microscopy/spectroscopy

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de la Materia Condensada. Fecha de lectura: 22-07-3013En esta tesis se presenta el estudio de dos moléculas aceptoras de electrones bien conocidas, TCNQ y F4-TCNQ, sobre grafeno epitaxial. El crecimiento y caracterización de sus propiedades electrónicas y magnéticas se realizó mediante Microscopía y Espectroscopia Túnel de Barrido (STM/STS) en Ultra Alto Vacío y a baja temperatura. El grafeno epitaxial se crece sobre Ru(0001) y Ir(111) mediante descomposición térmica de moléculas. A pesar de que en ambos casos la superficie de grafeno presenta un patrón de moiré, estos dos sistemas son complementarios en lo que se refiere a la interacción entre el grafeno y el metal. El balance entre las interacciones molécula-molécula y molécula-substrato es estudiada para ambas moléculas a diferentes recubrimientos mediante STM. El grafeno epitaxial nos permite la pasivación de la superficie altamente reactiva del metal permitiendo el estudio de moléculas individuales prácticamente inalteradas así como la formación de diferentes estructuras moleculares autoensambladas. La espectroscopia túnel de barrido a baja temperatura es utilizada para dar a conocer la estructura electrónica de estas capas moleculares. En el caso de las TCNQ sobre grafeno/Ir(111), las moléculas se mantienen prácticamente neutras debido a la débil interacción con el sustrato. Por otra parte, en el caso de las TCNQ adsorbidas en grafeno/Ru(0001), estos experimentos, en concordancia con cálculos DFT+D2, mostraron la ocupación parcial del LUMO de la molécula de TCNQ neutra. Este orbital se divide en dos orbitales con espines opuestos, SOMO y SUMO. El papel de la capa de grafeno es modular la hibridización entre el electrón desapareado transferido a la molécula y los electrones de conducción del Ru, dando lugar a un efecto Kondo dependiente de la posición de absorción. Esta dependencia es confirmada para recubrimientos mayores de TCNQ y para moléculas de F4-TCNQ en la misma superficie. Además, el efecto combinado de la interacción atractiva entre las moléculas de TCNQ y la ocupación parcial del LUMO da lugar a la formación de bandas intermoleculares extendidas espacialmente que permiten a las moléculas deslocalizar la carga adquirida. Estas bandas están divididas en espín, con sólo la banda de espín mayoritaria ocupada, como revelaron los cálculos DFT. La existencia del correspondiente orden magnético a largo alcance es detectado mediante experimentos de STM polarizados en espín a 4.6 K. Estos resultados son la primera evidencia experimental y teórica de la existencia de orden magnético a largoThis thesis presents a study of two well-known electron acceptor molecules, TCNQ and F4- TCNQ, deposited on epitaxial graphene. The growth and characterization of the electronic and magnetic properties of these systems have been performed by means of Low Temperature Scanning Tunneling Microscopy and Spectroscopy (STM/STS) in Ultra High Vacuum. A graphene layer is grown by chemical vapor deposition on Ru(0001) and Ir(111) surfaces. Although in both cases the graphene surface presents a moiré superstructure, these two systems are completely different from the graphene-metal interaction point of view. The relative strength between the molecule-molecule and molecule-substrate interactions is systematically studied for both molecules at different molecular coverages by means of STM. The epitaxial graphene passivates the highly reactive metallic surfaces allowing the study of almost unperturbed single molecules and the formation of self-assembly molecular structures. Low temperature scanning tunneling spectroscopy is used to unveil electronic structure of these molecular layers. In the case of TCNQ on graphene/Ir(111), the weak moleculesubstrate interaction keeps the molecules practically neutral. On the other hand, in the case of TCNQ deposited on graphene/Ru(0001), these experiments, in agreement with DFT+D2 calculations, reveal the partial occupation of the LUMO of the neutral TCNQ molecule. This orbital splits into a spin-up SOMO and a spin-down SUMO. We find that the graphene layer modulates the hybridization between the transferred unpaired electron and the Ru conduction electrons leading to a site dependent Kondo effect. This dependence is further confirmed for higher TCNQ coverages and for F4-TCNQ molecules on the same surface. In addition to that, the combined effect of the attractive interaction between TCNQ molecules and the partial occupation of the LUMO gives rise to the formation of spatially extended intermolecular bands, that allow the molecules to delocalize the charge acquired. The bands are spin split, with only the majority spin band being occupied as revealed in the DFT calculations. The existence of the corresponding long-range magnetic order is detected by spin polarized STM at 4.6 K. These findings are the first experimental and theoretical evidence for the existence of long-range magnetic order in delocalized bands in a purely organic molecular monolayer