Light-triggered Catalytic Asymmetric Allylic Benzylation of Isatin-derived MBH Carbonates

The formation of new C-C bonds is among the most thriving fields of research in synthetic organic chemistry. In fact, novel C-C bond-forming transformations give access to new, unprecedented carbon backbones. An even more challenging goal is the development of synthetic methods able to forge quaternary all-carbon centres in an enantioselective fashion, that allow the synthesis of complex, valuable molecules like natural products. The growing attention to environment is now directing research towards greener chemical solutions: atom economy, environmentally friendly solvents, mild reaction conditions, and the use of renewable resources. Photochemistry and organocatalysis, the two co-protagonists of this thesis project, are in full agreement with the principles of Green Chemistry. The development of light-triggered transformations along with the employment of purely organic chiral catalysts allow milder reaction conditions, thus energy saving. This thesis project is focused on the development and the optimisation of the asymmetric allylic alkylation reaction, using non-stabilised, photo-generated nucleophiles. To the best of our knowledge, only very few examples of asymmetric allylic alkylation with non-stabilised nucleophiles have been reported, and none of them through an organocatalysed strategy. For this purpose, Morita-Baylis-Hillman (MBH) carbonates derived from isatin, a biologically active molecule, are selected as electrophiles. Starting from racemic MBH carbonates, quaternary all-carbon stereocentres are created in an enantioselective fashion via a dual activation strategy. The chiral organocatalyst activates the electrophile and is responsible for the stereoinduction event, while light irradiation activates the 2-methylbenzophenone derivative to form the photoenol intermediate as non-stabilised C-nucleophile. In addition, the reaction is also optimised under a microuidic photoreactor for in-flow continuous synthesis.