Reacciones de CO2 con nucleófilos carbonado y nitrogenados: aplicaciones en síntesis

Las reacciones de carboxilación de nucleófilos carbonados y nitrogenados, así como de descarboxilación de los productos presentan una notable complejidad mecanística que sigue siendo objeto de discusión actualmente. El objetivo general del presente estudio plantea la exploración de estas reacciones y su eventual aplicación en síntesis. En el primer capítulo se describen las reacciones de carboxilación de aniones enolato y la química de los β-cetocarboxilatos alcalinos correspondientes en el contexto de su aplicación en reacciones de alquilación monoselectiva. Los resultados muestran el impacto de la agregación y los equilibrios ácido-base sobre la evolución de los intermedios de reacción, y cómo el control de estos factores permite llevar a cabo la monoalquilación selectiva de enolatos derivados de cetonas. El segundo capítulo aborda la química de carbamatos alcalinos en medio orgánico y explora las posibilidades de aplicación como bases en síntesis orgánica. Los resultados ilustran cómo la concentración de CO2 en el medio de reacción afecta a los equilibrios de transferencia de protón y CO2 entre las especies implicadas. El capítulo tercero estudia las reacciones de transferencia electrónica fotosensibilizada de aminas con CO2 y las vías de reacción que tienen lugar en estos procesos. Los resultados proporcionan información relevante para la comprensión de las reacciones de carboxilación y descarboxilación de nucleófilos carbonados y nitrogenados.Carboxylation reactions of carbon and nitrogen nucleophiles, as well as decarboxylation pathways of the corresponding products show significant mechanistic complexity which is still under discussion nowadays. The general aim of the present study addresses the exploration of these reactions and their eventual future synthesis application. The first chapter describes the carboxylation reactions of enolate anions and the chemistry of the corresponding alkaline β-ketocarboxylates in the context of selective monoalkylation reactions. The results show the impact of aggregation and acid-base equilibriums on the evolution of the reaction intermediates, and how to control these factors for achieving the selective monoalkylation of enolates derived from ketones. The second chapter addresses the chemistry of alkaline carbamates in organic solvents, exploring the application of these species as bases in organic synthesis. The results illustrate how CO2 pressure affects proton and CO2 transfer equilibriums between the species involved. Finally, the third chapter studies photoinduced electron transfer reactions of tertiary amines with CO2 and the reaction pathways occurring in these processes. The results provide relevant information for understanding the carboxylation-decarboxylation reactions of carbon and nitrogen nucleophiles

Photolysis of tertiary amines in the presence of CO2: the paths to formic acid, α-amino acids, and 1,2-diamines

The photolysis of triethylamine (1a) in the presence of carbon dioxide leads to the hydrogenation of CO2, the α-C-C coupling of triethylamine (1a), and the CO2-insertion into the α-C-H σ-bond of amine 1a. This reaction is proposed to proceed through the radical ion pair [R3N·+·CO2·-] generated by the photoionization of amine 1a and the electron capture by CO2. The presence of lithium tetrafluoroborate in the reaction medium promotes the efficient and stereoselective α-C-C coupling of 1a by enhancing the production of α-dialkylamino radicals and the isomerization of N,N,N',N'-tetraethylbutane-2,3-diamine (4a)

Reactivity of lithium β‑ketocarboxylates: the role of lithium salts

Lithium beta-ketocarboxylates 1(COOLi), prepared by the reaction of lithium enolates 2(Li+) with carbon dioxide, readily decarboxylate in THF solution unless in the presence of lithium salts, in which case they are indefinitely stable at room temperature in inert atmosphere. The availability of stable THF solutions of lithium beta-ketocarboxylates 1(COOLi) in the absence of carbon dioxide allowed reactions to take place with nitrogen bases and alkyl halides 3 to give alpha-alkyl ketones 1(R) after acidic hydrolysis. The sequence thus represents the use of carbon dioxide as a removable directing group for the selective monoalkylation of lithium enolates 2(Li+). The roles of lithium salts in preventing the decarboxylation and disproportionation reactions of lithium beta-ketocarboxylates 1(COOLi), and in determining the course of the reaction with bases and alkyl halides 3, are discussed

Metal-free visible light-promoted synthesis of isothiazoles: a catalytic approach for N-S bond formation from iminyl radicals under batch and flow conditions

A sustainable synthesis of isothiazoles has been developed using an α-amino-oxy acid auxiliary and applying photoredox catalysis. This simple strategy features mild conditions, broad scope and wide functional group tolerance representing a new enviromentally friendly option to prepare these highly valuable heterocycles. Furthermore, the synthetic value of the method is highlighted by the preparation of a natural product derivative and the implementation of the reaction in a continuous flow setupWe acknowledge the financial support by the Spanish Government (RTI2018-095038-B-I00) and ERC (ERC-CG, 647550

A CONTINUOUS FLOW SULFURYL CHLORIDE BASED REACTION – SYNTHESIS OF A KEY INTERMEDIATE IN A NEW ROUTE TOWARD EMTRICITABINE AND LAMIVUDINE

We demonstrate a continuous two-step sequence where a sulfenyl chloride is formed, trapped by vinyl acetate and chlorinated further via a Pummerer rearrangement. This sequence produces a key intermediate in our new approach to the oxathiolane core used to prepare the anti-retroviral medicines Emtricitabine and Lamivudine. During batch scale-up to tens of grams, we found that the sequence featured a strong exotherm, temperature and pressure sensitivity, and evolution of hydrogen chloride and sulfur dioxide. These reactions are ideal candidates for implementation in a continuous, mesoscale system for the sake of superior control. In addition, we found that fast reagent additions at controlled temperatures decreased byproduct formation. Herein, we discuss the flow implementation and the final reactor design that led to a 141g/h throughput system. </p

Photolysis of Tertiary Amines in the Presence of CO₂: The Paths to Formic Acid, α‑Amino Acids, and 1,2-Diamines

The photolysis of triethylamine (<b>1a</b>) in the presence of carbon dioxide leads to the hydrogenation of CO₂, the α-C–C coupling of <b>1a</b>, and the CO₂ insertion into the α-C–H σ-bond of amine <b>1a</b>. This reaction is proposed to proceed through the radical ion pair [R₃N^•+·CO₂^•–] generated by the photoionization of amine <b>1a</b> and the electron capture by CO₂. The presence of lithium tetrafluoroborate in the reaction medium promotes the efficient and stereoselective α-C–C coupling of <b>1a</b> by enhancing the production of α-dialkylamino radicals and the isomerization of <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetraethylbutane-2,3-diamine (<b>4a</b>)

Supramolecular Chemistry of Carbon Nanotubes

International audienceThis chapter aims to present recent examples of supramolecular functionalization of carbon nanotubes. The non-covalent functionalization appears as a solution for the future applications in nanotechnologies since it allows the functionalization and manipulation of nanotubes without the introduction of sp 3 defects in the π-conjugated system. Thus, the optical and electronic properties of the nanotubes remain preserved. In the first part of this chapter, we present the use of surfactant for the dispersion of nanotubes and its application for sorting. Then we report several examples of functionalization of nanotubes based on π-stacking interactions with pyrene derivatives. Finally, in the last part we review the wrapping of photo/electroactive polymers around the nanotube sidewalls. We put a particular focus on polyflurorene-based polymers and we show their utilization for the separation of nanotubes in diameter and chirality