Asymmetric Transition Metal-Catalysed Alkyl Addition to Imines : High throughput screening of iridium and rhodium catalysts

The research project presented in this book deals with the development of the alkylation of protected aldimines using organoaluminium and organozinc compounds as alkylating agents. To this end, efforts have been focused into the methylation reaction using trimethylaluminium and dimethylzinc. The identificaton of suitable metal catalysts as well as diphosphine ligands was carried out by means of extensive high throughput screening. A preliminary screening of a range of aldimines bearing different protecting groups aimed at selecting the most interesting substrate. The diphenylphosphinoyl (dpp) protecting group turned out to be the best activating group for aldimines tested within the framework of this study. The presence of a phosphorus atom on this protecting group is a feature which was notably used to determine the enantiomeric excess by 31P NMR spectroscopy, thus providing a novel and efficient screening tool at disposal. On the one hand an iridium catalyst proved to be efficient when associated to AlMe3 or DABAL-Me3 in the non-enantioselective 1,2-addition. On the other hand, a rhodium catalyst was found to be able to catalyse the enantioselective 1,2-addition of Me2Zn.