Seeking Passe-Partout in the Catalytic Asymmetric Aziridination of Imines: Evolving Toward Substrate Generality for a Single Chemzyme

The asymmetric catalytic aziridination reaction (AZ reaction) of imines derived from dianisylmethyl (DAM) amine and tetra-methyldianisylmethyl (MEDAM) amine were examined with boroxinate catalysts prepared from both the VANOL and VAPOL ligands. This included an evaluation of different protocols for the preparation of the catalyst. The AZ reaction of DAM and MEDAM imines prepared from nine different aryl and aliphatic aldehydes were examined. The MEDAM imines were superior to the DAM imines in the AZ reaction, giving much higher asymmetric inductions and higher overall yields of aziridines. The MEDAM imines were found to also be superior to the previously studied diphenylmethyl (benzhydryl or Bh) and tetra-tert-butyldianisylmethyl (BUDAM) imines especially for imines derived from aliphatic aldehydes. The average asymmetric induction over the nine different MEDAM imines studied was 97% cc with the VAPOL catalyst and 96% cc with the VANOL catalyst. The MEDAM imines can be deprotected to give N-H aziridines in all cases except for some electron-rich aryl aldehydes. The MEDAM imines are much more reactive than benzhydryl imines, and this was most evident when a diazoacetate ester is replaced by a diazoacetamide. The less reactive diazoacetamides give very low yields in their reactions with benzhydryl imines but high yields with MEDAM imines.