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

When alkene-containing substrates are functionalized using metal nitrenoid complexes, aziridination is typically the favored 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 perform 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 Cinchona alkaloid-derived 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 natural stereochemistry. It also reveals that chemoselectivity and enantioselectivity are intrinsically linked, fully in line with our hypothesis of the reaction being guided by attractive noncovalent interactions.