AMIDYL RADICALS IN LIGHT PROMOTED REACTIONS

The present thesis work is devoted to the study of four different topics as depicted in Figure 1, the enantioselective addition of amidyl radicals in α position to aldehydes, (Figure 1A), the addition of N lactam radicals to nucleophiles such as heteroarenes, arenes and aldehydes (Figure 1B), the preliminary investigation of the enantioselective addition of N-acetyl radicals to olefins (Figure 1C) and the development of the enantioselective α-SCF3 addition to β-ketoesters (Figure 1D). Figure 1 Research outline. In particular, Chapter 1 provides an overall introduction to the main topics encountered in this PhD thesis: Chapter 1.1 deals with a general definition of photocatalysis, the main photocatalytic activation pathway and same selected literature example to compare light catalysed reactions with and non-light catalysed reactions. The nitrogen radicals are introduced and classified in Chapter 1.2 with an historical overview of the previous literature work, while Chapter 1.3 reports the main advantages to perform a photochemical transformation exploiting the flow technology. Chapter 2 is focused on the results obtained and it is divided in four main topics plus an appendix (illustrated in Figure 1): Chapter 2.1 deals with the enantioselective addition of amidyl radicals to aldehydes employing an imidazolidinone organocatalyst to promote the selectivity of the transformation. Moreover, we report also the development of the flow process for this transformation. Chapter 2.2 concerns the development and the study of a new class of amidyl radicals: the N lactam radicals. We are able to synthetize suitable nitrogen radical precursors and employ them in the photocatalytic addition of γ, δ, ε lactam radicals to heteroarenes, arenes and aldehydes. Moreover, we perform a wide reaction scope and a deepen mechanism investigation. After having deeply studied the employment of these new radicals, we selected a pharmaceutical target to applied the N lactam radicals and the results are reported in Chapter 2.3. A new photocatalytic synthesis of Levetiracetam, an antiepileptic drug, was developed. Chapter 2.4 reports the idea and the initial attempts done to develop the enantioselective addition of N-acetyl radicals to electronrich olefins. The experiments reported in the Appendix concerned the enantioselective addition of the enantioselective α-SCF3 addition to β-ketoesters were executed at the beginning of the PhD period before starting work on amidyl radicals in light promoted reactions. Chapter 3 provides all the experimental part of the PhD thesis including the synthetic procedures, 1H-NMR, 19F-NMR and 13C-NMR of the unknown compounds and the HPLC traces of the enantiomeric excess of the asymmetric transformations.

Grantor dc:publisher

Università degli Studi di Milano

Year dc:date

2024

Author dc:creator

• BOSELLI, MONICA FIORENZA

Contributors dc:contributor

• tutor: A. Puglisi ; co-tutor: M. Benaglia ; coordinatore: D. Passarella
• M.F. Boselli
• PUGLISI, ALESSANDRA
• PASSARELLA, DANIELE

• photocatalysi
• Nitrogen radical
• amidyl radical
• Flow Chemistry
• Settore CHIM/06 - Chimica Organica

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

http://dx.doi.org/10.13130/boselli-monica-fiorenza_phd2024-06-14
10.13130/boselli-monica-fiorenza_phd2024-06-14

OAI identifier oai:identifier

oai:air.unimi.it:2434/1055472