New Trends in Organocatalysed and Photochemical Vinylogous Transformations. Access to Novel Bioactive Heterocyclic Chemotypes

Abstract

The work here presented is focused on the application of organocatalysis as a powerful means to unlock the vinylogous reactivity of different poly-dentate substrate donors, thereby allowing new chemical transformations. More than eighty years ago, Reynold Clayton Fuson, an American chemist, first enunciated the principle of vinylogy realizing that, in a system of conjugate double bonds, the electronic properties of a leading functional group can be propagated along the C(sp2)-chain toward remote positions. This concept has been extensively exploited throughout the past decades as an opportunity to fuel new chemical transformations toward increasing molecular complexity. In this scenario, my efforts have been devoted to shed new light onto this established chemistry, by applying vinylogous chemistry, merged with organocatalysis, within new challenging frontiers. The first part of this thesis, the Introduction, is intended to introduce the reader for well-understanding the experimental work that I performed during my PhD, furnishing basic concepts of organocatalysis, photocatalysis, and vinylogous reactivity. The last part of the Introduction deepens two hot-topics of the vinylogous chemical realm on which I worked and that, from a personal perspective, represent charming fields that deserve to be further broadened in the future. Subsequently, Chapter II and Chapter III describe the development of two new protocols where the principle of vinylogy elegantly allows for the stereoselective generation of two new chiral and heterocyclic uracil- and imidazole-based chemotypes featuring in-cycle stereocenters. The chemistry involves a previously reported uracil-pronucleophile and an inedited imidazole-based pro-diene substrate to be employed in stereoselective and organocatalysed [4+2] cycloadditions with suitable dienophiles, to give rise to new classes of chiral tetrahydroquinazolindiones and dihydrobenzimidazoles, respectively. Importantly, several uracil-based congeners also revealed promising antiviral activity. Finally, the project described in Chapter IV discloses about the exploitation of the principle of vinylogy within the radical chemistry by using chiral dienamines as radical traps. In particular, a rare example of a photochemical-driven process is described, where the dual synergistic action of organocatalysis and dithiocarbamate catalysis allows for the stereoselective γ-functionalization of α-branched enals.