Stereoselective cis -Vinylcyclopropanation via a Gold(I)-Catalyzed Retro-Buchner Reaction under Mild Conditions

A highly stereoselective gold(I)-catalyzed cis-vinylcyclopropanation of alkenes has been developed. Allylic gold carbenes, generated via a retro-Buchner reaction of 7-alkenyl-1,3,5-cycloheptatrienes, react with alkenes to form vinylcyclopropanes. The gold(I)-catalyzed retro-Buchner reaction of these substrates proceeds by simple heating at a temperature much lower than that required for the reaction of 7-aryl-1,3,5-cycloheptatrienes (75 °C vs 120 °C). A newly developed Julia−Kocienski reagent enables the synthesis of the required cycloheptatriene derivatives in one step from readily available aldehydes or ketones. On the basis of mechanistic investigations, a stereochemical model for the cis selectivity was proposed. An unprecedented gold-catalyzed isomerization of cis– to trans-cyclopropanes has also been discovered and studied by DFT calculations

Oxidative Transfer Reactions at a Metal-Metal Bond

Strained, three-membered rings were found to undergo oxidative addition to [iPrNDI]Ni2(C6H6) complex [NDI = napthyridine-diimine). Activation of the C-N bond of 1-tosyl-2-vinylaziridine generates a dinickel metallacyclic product. Based on this reactivity, the [iPrNDI]Ni2(C6H6) complex was shown to be a highly active catalyst for rearranging vinylcyclopropanes to cyclopentenes. Notably, 2-phenyl-1-vinylcyclopropane undergoes regioselective activation at the less hindered C–C bond in contrast to the non-catalytic thermal rearrangement. The dinuclear complex was also found to readily rearrange hetero-atom containing cyclopropanes to their linear products. DFT calculations provide insight into the ability of the Ni–Ni bond to stabilize key intermediates and transition states along the catalytic pathway. Hetero-atom abstraction was also observed in the activation of other strained, three-membered rings with the [iPrNDI]Ni2(C6H6) complex. Crystal structures were obtained from the activation of sulfur containing heterocycles and their characteristics are currently being investigated to design catalytic desulfurization reactions

Some synthetic efforts in small ring chemistry

Cyclopropylcyclobutene was prepared via the intermediate dicyclopropylcarbinyl carbene which was generated by the thermal decomposition of the sodium salt of dicyclopropylketone p-toluenesulfonylhydrazone. The successive thermal isomerization of cyclopropylcyclobutene to 2-cyclopropyl-1, 3-butadiene and to vinylcyclopentene was studied. Kinetic data were obtained for the cyclopropylcyclobutene to 2-cyclopropyl-1, 3-butadiene isomerization in the gas phase. Decomposition of the sodium salt was studied in different solvent systems at 130°, but bicyclo(1.1.0)butane ring formation was not a major reaction pathway under conditions similar to those used in the decomposition of cyclopropylcarboxaldehyde p-toluenesulfonylhydrazone. Attempts to synthesize the compounds bicyclo-(2.2.0)hex-1(4)-ene and bicyclo(2.2.0)hex-1-ene via carbenoid intermediates were hampered by difficulties in preparing the necessary precursors

SIGMATROPIC REARRANGEMENTS OF DIVINYLCYCLOPROPANES AND CYCLIZATIONS INVOLVING β-ELIMINATION OF SULFONYL RADICALS

The first chapter of this dissertation describes the synthesis and reactions of a family of 1,1-divinylcyclopropanes, including the discovery and studies of several sigmatropic rearrangement cascades. Also discussed is the radical [3+2] cyclization of 1,1-divinylcyclopropanes with the potential for memory of chirality. The second chapter deals with the elimination of sulfonyl radicals during radical cyclizations of ene-sulfonamides. A family of polycyclic imines and a family of oxindole products were synthesized from polycyclic ene-sulfonamide precursors

From molecular photocatalysis to organocatalytic materials

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 18-10-2019Esta tesis tiene embargado el acceso al texto completo hasta el 18-04-2021La fotocatálisis mediada por luz visible es un campo que está sufriendo un gran desarrollo en las últimas décadas y está permitiendo desarrollar metodologías para crear ciertos tipos de enlaces químicos difíciles de crear por métodos térmicos convencionales. La presente tesis doctoral ha buscado continuar en esta línea y desarrollar metodologías fotocatalíticas que aporten ventajas en las reacciones de transposición de ciclopropanos y la alilación de nucleófilos. Así, se ha descubierto que la acción del fotocatalizador Ir(dFppy)3 junto con la irradiación de luz azul es capaz de promover la transposición de formilciclopropanos y vinilciclopropanos para la obtención de 2,3-dihidrofuranos y ciclopentenos, respectivamente. Estudios mecanísticos revelan que se trata de un proceso de transferencia de energía y que un grupo funcional nitro ha de estar anclado al ciclopropano para que la reacción funcione. Este método permite la transposición de ciclopropanos con sustituciones diferentes a los ciclopropanos usados en transposiciones térmicas convencionales. Se ha desarrollado un método de alilación de nucleófilos mediante el uso de fotocatalizadores orgánicos. El uso del fotocatalizador 10-fenil-10H-fenotiacina (PTH) junto con irradiación con luz ultravioleta permite la obtención del nucleófilo alilado con configuración Z. Por otro lado, el uso del fotocatalizador 3-(4-metoxifenil)-10-fenil-10H-fenoxacina, junto con irradiación de luz azul, lleva a la obtención de nucleófilo alilado con configuración E. Este método fotocatalítico permite la alilación de diferentes nucleófilos (heterociclos, aminas y alcoholes) sin usar catalizadores metálicos y permite el control de la configuración del doble enlace, lo cual no es frecuente con métodos de alilación convencionales, en los cuales es necesario un catalizador metálico y en la gran mayoría de casos sólo se obtiene el isómero E. Por otro lado, en los últimos años ha habido un gran desarrollo de los materiales MOF (MetalOrganic Frameworks) y COF (Covalent Organic Framework), cuya porosidad y fácil modulación de su estructura química ha permitido encontrar múltiples aplicaciones. La segunda parte de presente tesis doctoral se desarrolla en el ámbito de las aplicaciones catalíticas de estos materiales. Se ha sintetizado un nuevo MOF, análogo al IRMOF-16, que contiene en sus ligandos el grupo funcional escuaramida, conocido por catalizar reacciones orgánicas mediante la formación de enlaces de hidrógenos con el substrato. El hecho de que los grupos escuaramidas estén inmovilizados en las paredes de materiales porosos mediante enlace covalente evita la “autoasociación” de estos grupos catalíticos, dejándolos completamente libres a la interacción con el sustrato, aumentando su eficiencia catalítica. Este material es capaz de catalizar la reacción de apertura de epóxidos por ataque nucleófilo de anilinas. La catálisis es más efectiva que usando un catalizador de escuaramida homogéneo. Finalmente se ha investigado la funcionalización mediante interacciones supramoleculares de los poros de un COF con pequeñas moléculas organocatalíticas. Se ha elegido el COF-300 para llevar a cabo el estudio. El material funcionalizado con moléculas de ácido acético en su interior era capaz de catalizar la reacción de apertura de epóxidos con aminas. El material funcionalizado con moléculas de trietilamina y ácido acético en sus poros era capaz de catalizar la condensación de Knoevenagel entre malonitrilo y aldehídos aromáticos.La financiación de este trabajo ha provenido del Ministerio de Economía y Competitividad (CTQ-2015-64561-R) y del Consejo Europeo de Investigación (ERC-CG, número de contrato 647550)

Photochemical Reactions of Acylsilanes Towards the Construction of Carbon-Carbon Bonds

Photochemistry is a field of chemistry which has fascinated chemists for centuries. The access to the photoexcited state of molecules allows otherwise unattainable reactivity and access to completely novel structures. The use of light as a reagent in organic synthesis can also circumvent the need of toxic or expensive reagents commonly used in traditional synthetic chemistry, making photochemistry an attractive tool in the context of Green Chemistry. Acylsilanes are a class of compounds with rich photochemistry. They possess the unique ability to undergo photorearrangement to reactive nucleophilic siloxycarbenes. While this metal-free method for carbene generation is highly promising, the number of known efficient reactions they undergo is limited and underexplored. In this thesis, a variety of acylsilanes have been synthesized in order to further explore and expand their known photo reactivity and obtain new complex structures via C-C bound forming photoreactions. A regioselective intramolecular [2+2]-photocycloaddition of benzoyl(allyl)silanes was developed to yield novel silacyclopentanes, compounds that may be used as silicon bioisosteres of cyclopentanes. Additionally, a novel formal (4+1)-cycloaddition of photogenerated siloxycarbene with electrophilic dienes was discovered, allowing the synthesis of highly functionalized cyclopentenes and expanding the limited reactivity of such carbenes with olefins. During the synthesis of acylsilanes via the dithiane umpolung methodology an autooxidative condensation of lithiated aryl dithianes was serendipitously uncovered, which yielded complex α-thioether ketone orthothioesters, some of which present strong cytotoxic activity against glioblastoma cancer cell lines

The synthesis and chemistry of strained bicyclic systems

A facile route to bicyclo(2.1.1)hexanes was developed involving the intramolecular photocyclization of 1, 5-hexadien-3-one to bicyclo(2.1.1)hexan-2-one. A study of the chemistry of bicyclo-(2.1.1)hexan-2-one was undertaken. Deuterium exchange and borohydride reduction demonstrated the strain present in the ketone. Further evidence was obtained from the failure to introduce substituents alpha to the carbonyl group, a usually facile reaction and a necessary step in desired ring contraction studies. After numerous unsuccessful attempts to introduce a double bond into the bicyclo(2.1.1) hexane system, a successful route to the parent bicyclo(2.1.1) hexene was achieved. The key step involved dehydrohalogenation of 2-bromobicyclo(2.1.1)hexane. Some preliminary studies of the olefin have been carried out and its thermolysis studied

The thermal decomposition of perfluorocyclopropane

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