Aziridine-containing molecules are significant both as biologically active natural products and as versatile synthetic intermediates. Because of the pharmaceutical potential of these compounds and the current lack of general, one-step methods to form them enantioselectively, a new catalytic, asymmetric aziridination method is proposed. Specifically, this project will develop a one-step transformation of readily accessible enones and unsaturated imides into enantioenriched aziridines using easily prepared catalysts and readily available nitrogen sources. Because chiral (salen)AI(lll) catalysts provide high enantioselectivity in conjugate addition reactions, these catalysts will be used to activate the unsaturated substrates. An ambiphilic nitrogen source, such as Chloramine-T, will allow both C-N bonds to be formed in one synthetic step. To exemplify the utility of this reaction, this aziridination will be used to make both synthetic intermediates and a small molecule with anti-leukemia activity. This practical method to form enantioenriched aziridines will facilitate synthesis and biological testing of new aziridine compounds, potentially leading to new medicines. This proposal seeks to develop a general, one-step method for the preparation of three-atom rings containing carbon atoms and one nitrogen atom. These rings are present in medically important compounds such as the anti-cancer drug mitomycin C and are used in the preparation of other chemicals with biological activity. This practical method will facilitate the synthesis of these known biologically active molecules as well as allow the rapid preparation of new compounds with anti-cancer or other medicinal properties.
| Watson, Mary P; Jacobsen, Eric N (2008) Asymmetric intramolecular arylcyanation of unactivated olefins via C-CN bond activation. J Am Chem Soc 130:12594-5 |
