INVESTIGATION OF NOVEL CATALYTIC TRANSFORMATIONS USING BIO-HYBRID AND TRANSITION METAL CATALYSIS

Abstract

This thesis is focused on the development of new catalytic tools to access complex structural scaffolds with a special emphasis given to heterocyclic compounds. The first chapter presents our work in the field of DNA-based asymmetric catalysis. After presenting how the DNA double-helix has been leveraged to promote and control various asymmetric transformations during the last decade, our efforts to extend this concept to new transformations are described. The behaviour of several processes was investigated, including a 1,3-dipolar cycloaddition, a Nazarov electrocyclisation, a conjugate silylation of enones and a propargylative dearomatisation. The chapter concludes with synthetic studies towards the asymmetric preparation of endiandric acid A. The second chapter is focused on the implementation of an enantioselective Michael addition/retro-Dieckmann sequence to the formation of a-functionalised alkenyl nitriles and related compounds, using both a bio-hybrid and a more traditional Lewis acid-catalysed approach. An introduction gives a brief overview of the various methods reported in the literature that allow a straightforward access to diversely substituted acrylic derivatives, emphasizing on the appeal of the tetrahydrothiophenone scaffold as an a-acrylate anion surrogate. Our results on the optimisation of a new enantioselective approach are then presented, followed by a discussion of the reaction’s scope. Finally, prospective studies on a potential application of our strategy to the synthesis of chromanes are described. The third chapter dwells on the preparation of phosphonated heterocycles, which hold a considerable biological interest. Building upon our group's previous work in the field of palladium-catalysed allylic alkylation, a straightforward and atomeconomic retrosynthetic approach was devised. We first developed a two-step synthesis of a-allyloxy phosphonate derivatives starting from the corresponding aldehydes. A subsequent ring-closing metathesis eventually delivered a set of oxygenated heterocycles. An investigation of potential late-stage functionalisations of the resulting products concludes the chapter.