Allylic Amination of Alkenyl Alcohols: Simultaneous Control of Chemoselectivity and Enantioselectivity in Nitrene Transfer Using Ion-Paired Catalysts

Abstract

When alkene-containing substrates are functionalized using metal nitrenoid complexes, aziridination is typically the favoured reaction outcome. In certain cases, careful catalyst control may permit allylic C-H amination but enantioselective protocols are very rare. This work describes the use of ion-paired Rh paddlewheel complexes to permit enantioselective allylic amination where the typically preferred aziridination outcome can be overcome by the directing effect operating between the catalyst and the alcohol functional group in the substrate. A survey of different functional groups reveals that in this case alcohols provide the optimum directing effect and we carry out a systematic study to elucidate the important features of the chiral cation associated with the anionic rhodium dimer. This reveals that the key inherent structural features of the natural alkaloids are necessary to obtain high enantio-and chemoselectivity, including the basic quinoline nitrogen and the free alcohol with the natural stereochemistry. It also revealed that chemoselectivity and enantioselectivity are intrinsically linked, fully in line with our hypothesis of the reaction being guided by attractive non-covalent inter-actions.