Phd in CHEMICAL SCIENCES

Thesis title: Advances in Asymmetric Synthesis: From Organocatalysis to Photocatalytic Strategies and Total Synthesis

This research work describes the development of a unified methodological strategy for asymmetric synthesis, built upon the synergy between organocatalysis, carbon dot-mediated photocatalysis, and the rational design of total synthesis. The goal was to establish sustainable, stereoselective, and scalable synthetic pathways for the construction of complex organic architectures. In the first part, the organocatalytic activation of fluorinated substrates was explored, a major synthetic challenge due to the strength of the C–F bond and the low nucleophilicity of fluoride. By exerting precise control over the catalytic environment and employing Lewis-base organocatalysts, it was possible to achieve highly selective transformations, demonstrating the efficiency of metal-free strategies in promoting enantioselective reactions on chemically demanding systems. In parallel, a carbon dot-based photocatalytic methodology was developed as a sustainable and effective approach for redox processes and asymmetric transformations under visible light. Carbon dots, easily synthesized and functionalized, exhibited excellent catalytic behavior, enabling high yields and significant enantioselectivities under mild, green, and experimentally straightforward conditions. The final part of the work focuses on the convergent total synthesis of (–)-parthenolide, selected as a model case to validate the coherence and robustness of the proposed approach. The synthetic sequence encompasses key transformations such as Horner–Wadsworth–Emmons reaction, Michael addition, and iodolactonization, the latter representing a crucial step for defining the diastereochemistry of the lactone ring and introducing strategically functionalized intermediates. Optimization studies revealed a clear balance between kinetic and thermodynamic control, with the ability to tune the diastereomeric ratio through the choice of solvent and reaction conditions. Overall, this work demonstrates that the combination of organocatalysis, photocatalysis, and asymmetric total synthesis constitutes a coherent and innovative synthetic strategy, capable of integrating sustainability, efficiency, and stereochemical precision in the preparation of complex and potentially bioactive molecular targets.