Additions catalytiques enantioselectives de reactifs diorganozinciques utilisant un ligand diphosphine monoxyde

This thesis mainly describes the use of a diphosphine monoxide ligand (BozPHOS) in enantioselective catalysis.;We first demonstrated that Me-DuPHOS could become partially oxidized into BozPHOS in the presence of copper salts. It was eventually established that the diphosphine monoxide ligand is the key for achieving reactivity and enantioselectivities for the addition of dialkylzinc reagents to N-(P,P-diphenylphosphinoyl)imines.;We then developed a novel strategy to efficiently prepare aliphatic alpha-enolizable N-(P,P-diphenylphosphinoyl)imines in situ from sulfinic acid adducts. Our method is the first to use this class of imines, once incorrectly perceived to be unstable, in enantioselective catalysis. So we have stretched the boundaries of the diethylzinc addition on N-(P,P-diphenylphosphinoyl)imines catalyzed by the BozPHOS·CuEt complex in order to synthesize chiral alpha,alpha-dialkylamines. Under heterogeneous conditions, we were finally able to generate aliphatic alpha-enolizable N-(P,P-diphenylphosphinoyl)imines prepared from the same precursors.;In response to a need from the pharmaceutical industry, we also sought to develop a protocol suited to the automated parallel synthesis of alpha-chiral amines. Still using BozPHOS as a chiral ligand, we elaborated simple and safe conditions to prepare these compounds in one pot from aldehydes. In the course of our study, we discovered that the (BozPHOS)2·CuOTf complex, which is air-stable and easy to manipulate, could be used as a precatalyst for the addition of imines.;We also showed that BozPHOS is a versatile ligand. For instance, it can be used for the addition of dialkylzinc reagents to beta-nitroalkenes. Overall, our developed procedure gives excellent yields and enantioselectivities, and, most notably, offers a nice complementary variation to other available methods.;Finally, we focused our attention on diorganozinc reagents, which are generally difficult to synthesize but essential in enantioselective catalytic reactions. We discovered that it was possible to generate them using zinc alcoholates or carboxylates with an organomagnesium reagent while inducting the residual precipitation of magnesium salts. In this manner, we were able to synthesize a wide scope of pure diorganozinc compounds dissolved in diethyl ether and to use them in diverse enantioselective catalytic reactions.;Keywords: amine, catalysis, enantioselectivity, imine, diorganozinc, reagents, diphosphine monoxide, nitroalkane, organocopper, tandem reaction...