Computational understanding of heterocyclisation reactions and synthesis of fluorinated isoquinolines

The present thesis deals with three different topics that have in common the formation of carbo- and heterocycles. As part of the CATMEC network (Catalytic Methods for Sustainable Synthesis. A Merged Experimental and Computational Approach), a multi-partner Innovative Training Network (ITN) European Joint Doctorate (EJD), the author of the thesis has carried out her work between the University of Sheffield and the Universidad del País Vasco. The whole work is organised as a synergy of experimental and computational studies to provide a deep understanding of the systems of interest. The first chapter contains an introduction about computational chemistry with a particular focus on DFT and its application. The second chapter regards asymmetric catalysis and includes two works made in collaboration with the group of Prof. Palomo at the Universidad del País Vasco. Bifunctional catalysts are employed to afford good levels of stereoselectivity in the α-functionalisation of challenging substrates, as substituted dienolates and trienolates, with olefins. Computational studies were performed mainly to rationalise the role of the catalyst. The third chapter in collaboration with the group of Prof. E. Occhiato at the Universitá degli Studi di Firenze presents two examples of gold catalysis applied to the [3,3]-rearrangement/Nazarov reaction of propargylic esters and the tandem Claisen rearrangement/hydroarylation reaction of propargyl vinyl ethers. The mechanisms of the reactions were studied computationally, as well as the effect of particular features in the substrates or in the catalysts. The last two chapters concern the synthesis of fluorinated isoquinolines and computational studies on particular issues encountered experimentally. The strategy employed is a two step reaction that includes a Rh-catalysed CH activation of oximes with difluoroalkenes and an electrocyclisation. The formation of an undesired side product induced us to undertake computational investigations on the electrocyclisation step.