Description of the thesis topic

Chiral amines are attractive targets in organic synthesis as useful building blocks to access complex scaffolds, but also due to their ubiquitous presence in numerous biologically relevant molecules. An extensive array of enantioselective methods has been developed to access these chiral amines using organic, organometallic or enzymatic catalysis. One alternative relies on the kinetic resolution of racemic mixture of amines, allowing to selectively convert one enantiomer while the other one ideally remains untouched. Organocatalyzed approaches were developed in this field, but they remain limited in terms of selectivities and applicability. The latter are mostly based on enantioselective N-acylations, where a chiral nucleophilic organocatalyst activates an electrophile to selectively transfer a functional group to one enantiomer. However, this strategy is greatly hampered by the strong and competitive nucleophilic character of the amine moiety, leading to background reactions resulting in poor selectivities.
This PhD project aims at tackling this challenge through the development of new organocatalyzed processes for the acylative kinetic resolution of amines, with the ambition of reaching high selectivities regardless the nucleophilicity of the amine derivatives employed. We also aim at exploiting even more challenging diamine derivatives through unusual activation modes, for their kinetic resolution (anti-diamines) as well as their desymmetrization (meso diamines). New classes of organocatalysts will be prepared and evaluated through innovative functionalization methods of (di)amines to achieve these objectives.

Work Context

The PhD work will be carried out within the Institut des Sciences Moléculaires de Marseille (iSm2), where four research teams work at the interface of synthetic chemistry, biochemistry, biology, and quantum chemistry.
The iSm2, a joint research unit (UMR7313) between the Centre National de la Recherche Scientifique (CNRS), the Ecole Centrale de Marseille (ECM), and Aix-Marseille Université (AMU), is located on the campus of the Faculty of Sciences of St-Jérôme, in Marseille.
The PhD will be conducted under the supervision of Drs. Julien Annibaletto (Associate Professor) and Cyril Bressy (Professor) within the stereO team, which specializes in the development of new synthetic methods in stereoselective catalysis. The team consists of 13 permanent staff members (professors, researchers, and engineers) as well as 11 PhD students and a postdoctoral researcher.