LIGHT AND ELECTRICITY: POWERFUL TOOLS FOR NEW SUSTAINABLE STEREOSELECTIVE SYNTHESIS

Aimed from the increasing need to identify new reactions, exploiting green energy sources, three different synthetic routes have been developed and analysed during this thesis work: the electrochemical dehydrogenative homo-coupling of β-Naphtylamines derivatives; the stereoselective cyclization of aryl-enones under homogeneous and heterogeneous conditions and the late-stage C-H iron (III) catalyzed electrophotochemical perfluoroalkylation. Chapter 1 provides a detailed description of the synthetic techniques employed. Chapter 1.1 explains how electrochemistry emerged in the field of organic chemistry thanks to technological development, underlining the principles of electrochemical reactions and its application in stereoselective transformations. The physical properties of light are reported in Chapter 1.2, as starting point to introduce Photoredox catalysis under homogeneous, heterogeneous and flow conditions. In addition, Chapter 1.3 shows a concise overview of electrophotocatalysis focusing on the difference between electrochemical mediated photoredox catalysis (e-PRC) and interfacial photoelectrochemistry (i-PCR). Chapter 2 concerns the electrochemical dehydrogenative homo-coupling of β-Naphtylamines derivatives: first, Chapter 2.1 reports a comprehensive description of the electrochemical homo- and cross- coupling between phenols and naphthols depicted in literature. Also, the behaviour of anilines and β-naphtylamines under electrochemical oxidative conditions is well analysed. With this literature in hands, we explored the possibility to carry out a stereoselective version of electrochemical homo-coupling using β-Naphtylamines bearing chiral auxiliaries. Chapter 2.2 is focused on the discussions of the results obtained for the intermolecular and intramolecular homo-coupling of chiral β-Naphtylamides and amines. Moreover, the possibility to remove the chiral auxiliary is also investigated and a proposed mechanism is well depicted. A brief resume of the data collected is reported in the conclusion (Chapter 2.3). The stereoselective cyclization of aryl-enones under homogeneous and heterogeneous conditions is outlined in Chapter 3. In particular, Chapter 3.1 consists in an historical background of the aryl-enones cyclization starting from the preliminary studies on the metal-catalysed cyclization to the metal-free photocatalyzed approaches. Considering the results reported, we envisioned to develop stereoselective methods for the metal-free photocyclization in order to synthetize trans-cyclopentane rings and functionalized bicyclo[3.2.0]heptane. Chapter 3.2 shows all the results obtained for the synthetic routes designed. First, we explored the enantioselective version of the photocyclization for the synthesis of trans-cyclopentane rings under homogeneous conditions. In order to address the stereochemical outcome from the reaction, a chiral auxiliary has been introduced on the aryl-enones to be cyclized and removed after the photocyclization. Then, with the aim to recover and reuse the catalyst, Eosin Y has been immobilized onto a sold support and the photocyclization carried in a heterogeneous environment. Lastly, at the end of the chapter, it is depicted the deep study on the stereoselective synthesis of bicyclo[3.2.0]heptanes. A concise resume of the results analysed is then reported in Chapter 3.3. The last part of this thesis, Chapter 4, is related to the topic explored during the visiting research period at University of Gӧttingen. In particular Chapter 4.1 points out on the role of fluorinated groups in medicinal chemistry. Moreover, electrochemical, photochemical and electrophotochemical approaches for the monofluoromethylation, difluoromethylation, trifluomethylation and perfluoroalkylation reported in literature have been selected and explained. Taking into account the advantages and the powerful of electrophotocatalysis, it is developed a versatile strategy to generate fluorinated radicals (both electrophilic and nucleophilic) through decarboxylative Iron (III) electrophotocatalysis. The discussions of the obtained results is shown in Chapter 4.2. After a brief description of the electrophotochemical set-up, this chapter presents the electrophotochemical method developed for the fluoroalkylation of xanthines derivatives and other bioactive molecules. In addition, the perfluoro C-H functionalization of Pirimidine and Purine analogues is carefully detailed. Chapter 4.3 collects the main results of the previous chapter giving a concise conclusion. Lastly, Chapter 5 provides all the experimental part of the PhD thesis including the synthetic procedures, 1H-NMR, 19F-NMR and 13C-NMR of the unknown compounds and the HPLC traces of the enantiomeric excess of the asymmetric transformations. Also, all the information regarding DFT calculations and kinetic studies are here reported.