Development of New Radical Cascades and Multi-component Reactions ― Application to the Synthesis of Nitrogen-containing Heterocycles

In this dissertation, Marie-Helene Larraufie develops original radical and pallado-catalyzed methodologies to enable the synthesis of several classes of bioactive nitrogen-containing heterocycles. New radical cascades employing the N-acylcyanamide moiety offer straightforward routes to quinazolinones and guanidines, as well as new insights into the mechanism of homolytic aromatic substitutions. In parallel, Larraufie expands the scope of visible light photoredox catalysis to the ring opening of epoxides and aziridines, thus providing new sustainable alternatives for the generation of radicals. Furthermore, in a collaborative effort with the Catellani group, the author investigates dual palladium/norbornene catalysis. First, she develops a C-amination coupling variant of the Catellani reaction with unprotected amines which provides an expeditious route to phenanthridines. Then, she examines the influence of the chelating effect on Pd(IV) intermediates reactivity with the help of experimental studies and DFT calculations. The work in this thesis has resulted in numerous publications in high impact journals.The clarity and depth of the experimental section will be useful for students and researchers working in this field.

Marie-Helene Larraufie graduated in 2008 from Ecole Superieure de Physique et de Chimie Industrielles (ESPCI-ParisTech). After an M.Sc. in organic and bioorganic chemistry at the Universite Pierre et Marie Curie in Paris, she joined the laboratory of Prof. Malacria for her Ph.D. studies. Her doctoral research under the direction of Prof. Fensterbank, Dr. Lacote and Dr. Ollivier focused on radical chemistry and pallado-catalyzed multi-component reactions. She defended her Ph.D. in 2011 and is now undertaking postdoctoral studies with Dr. B. Stockwell at Columbia University (New York, USA) thanks to a fellowship from Association pour la Recherche sur le Cancer.