Synthese de nouveaux ligands hemilabiles chiraux: Application a la synthese enantioselective.

摘要

Hemilabile ligands are unique due to the presence of a soft and a hard coordinating site in the same molecule. In the case of phosphine-type ligands, the phosphorus atom provides the soft site and can coordinate strongly to a transition metal. On the other hand, the labile part, which is represented by the hard site, will coordinate weakly to the same metal. Several labile functionalities are known in the literature such as oxygen, nitrogen, sulfur or carbon-based groups. Due to these properties, hemilabile ligands exhibit interesting reactivity for homogeneous catalysis and are complementary to classic ligands.;In order to gain insight about the origin of the specificity of Me-DuPHOS(MO) in this catalytic asymmetric reaction, new hemilabile ligands have been synthesized and tested in the addition of diethylzinc to the N-phosphinoylimine derived from benzaldehyde. Thus, these ligands allowed us to screen three main structural characteristics: the P-P linker, the projection of chirality from the phospholane unit and the hard site. This study revealed that the modification of the P-P linker led to comparable results to Me-DuPHOS(MO). Moreover, it demonstrated that the soft site is solely responsible for the excellent enantioselectivities observed. Furthermore, it showed that phosphine oxide-type hard site is optimal. This work also permitted the identification of new hemilabile ligands with simpler structures that are as effective as Me-DuPHOS(MO).;At the same time, precursors to functionalised aliphatic N-phosphinoylimines were synthesized. After the catalytic asymmetric addition of di-organozinc reagents, these compounds led to the synthesis of N-heterocycles such as pyrrolidine/piperidine and pyrrolidinone/piperidinone as well as alpha-chiral allylic amines. Finally, tetrahydroisoquinoline derivatives bearing a chiral center at Cl were synthesized with excellent enantiomeric excesses.;Keywords: Hemilabile ligand · Diphosphine monoxide · Monophosphine · Asymmetric catalysis · N-Heterocycle · Allylic amine · Tetrahydroisoquinoline;Me-DuPHOS(MO), which was developed in Professor Charette's group, belongs to this category and proved to be the ligand of choice in the catalytic asymmetric addition of di-organozinc reagents to N-phosphinoylimines.