EXPLORING UNPRECEDENT SYNTHETIC ROUTES FOR CHIRAL AMINO DERIVATIVES

This PhD thesis focuses on the development of unprecedented synthetic strategies for the preparation of chiral amino derivatives through the integration of photoredox catalysis, organocatalysis, transition-metal catalysis, and continuous-flow chemistry. The work explores the synthetic potential of light-driven processes to access reactive open-shell intermediates under mild and sustainable conditions, enabling transformations that are difficult or inaccessible using conventional two-electron pathways. A major part of this research is devoted to the generation and exploitation of nitrogen-centered radicals, with particular emphasis on nitrogen lactam radicals. Novel precursors and activation strategies were developed to access these intermediates under visible-light photoredox conditions. Their reactivity was investigated in asymmetric organophotoredox processes, leading to the enantioselective α-functionalization of aldehydes. This methodology enables the direct construction of C–N bonds with high stereocontrol and was successfully applied to the synthesis of pharmaceutically relevant compounds, including a key intermediate of levetiracetam. The thesis also explores metallaphotoredox catalysis as a powerful platform for complexity-building reactions. In particular, deoxygenative arylation strategies were applied to the synthesis of dopamine-like compounds, both in batch and continuous-flow conditions, demonstrating the advantages of flow chemistry in terms of efficiency, scalability, and reaction control. Additional studies include asymmetric reductions and functional group manipulations carried out in collaboration with industry, as well as research activities conducted during an international research stay at the university of Cologne, covering asymmetric epoxidation and the development of novel cross-linking reagents for protein structure analysis. Overall, this work highlights the versatility of dual catalytic strategies and photochemical approaches for the sustainable synthesis of chiral nitrogen-containing molecules, offering new tools and perspectives for modern synthetic organic chemistry.

Grantor dc:publisher

Università degli Studi di Milano

Year dc:date

2026

Author dc:creator

• COLOMBO, ELEONORA

Contributors dc:contributor

• tutor: M. Benaglia ; cotutor: A. Puglisi ; coordinatore di dottorato: L. Prati
• E. Colombo
• BENAGLIA, MAURIZIO
• PRATI, LAURA

• Photocatalysi
• flow-chemistry
• nitrogen-radicals
• Settore CHEM-05/A - Chimica organica

Statement dc:rights

• info:eu-repo/semantics/embargoedAccess
• license:Creative commons
• license uri:http://creativecommons.org/licenses/by-sa/4.0/

Language dc:language

eng

Handle dc:identifier

https://hdl.handle.net/2434/1211315

OAI identifier oai:identifier

oai:air.unimi.it:2434/1211315