New strategies for enantioselective catalysis of photochemical reactions
- Autores: Lukasz Wozniak
- Directores de la Tesis: Paolo Melchiorre (dir. tes.)
- Lectura: En la Universitat Rovira i Virgili ( España ) en 2017
- Idioma: español
- Tribunal Calificador de la Tesis: Mariola Tortosa Manzanares (presid.), Alexandr Shafir (secret.), Jacek Mlynarski (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencia y Tecnología Química por la Universidad Rovira i Virgili
- Materias:
- Enlaces
- Tesis en acceso abierto en: hdl.handle.net TDX
- Resumen
The main objective of this doctoral thesis was to develop enantioselective, photochemical, organocatalytic reactions to provide new strategies for the synthesis of enantioenriched chiral compounds. Asymmetric catalysis of photochemical reactions is complicated by two main factors. The majority of organic compounds are unable to absorb light in the visible spectrum. Photochemical activation then requires UV irradiation, which demands using specialized apparatus. The second reason stems from the difficulties that accompany the reactivity control of photochemical reactions. The short-lived excited-states, achieved upon absorption of a photon, have low activation barriers for many transformations, which renders the control of the selectivity a severe problem. Despite these difficulties, developing stereocontrolled photochemical transformations is desirable because they often provide access to molecules that cannot be accessed by using alternative thermal processes.
This thesis presents novel strategies to carry out enantioselective transformations driven by visible light. The first part describes the development of an enantioselective photo-organocatalytic perfluoroalkylation of β-ketoesters. The transformation exploits the ground-state association of chiral enolates and perfluoroalkyl iodides, which results in the formation of photochemically active electron donor-acceptor (EDA) complexes. The process was performed under phase transfer catalytic (PTC) conditions, and the use of a chiral PTC catalyst allowed control of the enantioselectivity. A series of compounds with quaternary perfluoroalkyl stereocenters were synthesized with high enantiomeric excess and good yields. Preliminary mechanistic studies suggested that visible light excitation of the EDA complex initiates a chain reaction mechanism.
The second part of the thesis details a new strategy to design organocatalytic asymmetric cascade processes. The new approach combines the distinct reactivity of two chiral organocatalytic intermediates, namely the excited-state reactivity of chiral iminium ions with the ground-state reactivity of enamines. The photochemical organo-cascade reaction leads to stereochemically dense cyclopentanols with high yields and excellent selectivity, compounds that cannot be accessed by other methods. The observed excellent selectivity originated by an asymmetric amplification mechanism, which is due to a kinetic resolution process operative in the second step of the cascade process.
Thesis investigations employed modern organic chemistry techniques. Chemical structure identity and purity of all synthesized compounds were proven by means of nuclear magnetic resonance analysis (1H NMR, 13C NMR, 19F NMR). New molecules were fully characterized using NMR spectroscopy methods (1H NMR, 13C NMR, 19F NMR) and high resolution mass spectrometry (HRMS). In case of chiral molecules, optical rotation was measured using polarimeter and enantiomeric excesses were determined by high-pressure liquid chromatography (HPLC) or gas chromatrography (GC) with a chiral stationary phase. The absolute configuration of the stereogenic centers was assigned by comparison with literature (when possible), or by single-crystal X ray crystallographic analysis. For deeper understanding of the mechanism of the photochemical processes, quantum yield (Q) measurements were performed. The quantum yield identifies the number of molecules that undergoes a defined process per number of photons absorbed by the system. This delivered important information about the underlying mechanism of the light-triggered transformations. As the light source, simple compact fluorescent light bulbs or light emitting diodes (LED) were used, which made the experimental protocols operationally simple. More sophisticated light sources have been used for quantum yield measurement. This experiment required monochromatic irradiation, which was obtained using a Xenon Lamp equipped with band-pass and cut-off filters.
