Asymmetric nitrene transfer reactions: Sulfimidation, aziridination and C-H amination using azide compounds as nitrene precursors

Nitrogen functional groups are found in many biologically active compounds and their stereochemistry has a profound effect on biological activity. Nitrene transfer reactions such as aziridination, C-H bond amination, and sulfimidation are useful methods for introducing nitrogen functional groups, and the enantiocontrol of the reactions has been extensively investigated. Although high enantioselectivity has been achieved, most of the reactions use (N-arylsulfonylimino)phenyliodinane, which co-produces iodobenzene, as a nitrene precursor and have a low atom economy. Azide compounds, which give nitrene species by releasing nitrogen, are ideal precursors but rather stable. Their decomposition needs UV irradiation, heating in the presence of a metal complex, or Lewis acid treatment. The examples of previous azide decomposition prompted us to examine Lewis acid and low-valent transition-metal complexes as catalysts for azide decomposition. Thus, we designed new ruthenium complexes that are composed of a low-valent Ru(II) ion, apical CO ligand, and an asymmetry-inducing salen ligand. With these ruthenium complexes and azides, we have achieved highly enantioselective nitrene transfer reactions under mild conditions. Recently, iridium-salen complexes were added to our toolbox. Ru(CO)-salen complexes decompose azide compounds, atom-efficient nitrene precursors, under mild conditions and catalyze asymmetric nitrene transfer reactions such as sulfimidation, olefin aziridination and C-H amination in highly enantioselective manners. The reactions are chemoselective and the C-H amination occurs at benzylic and allylic positions in a highly regioselective manner. For example, 1-ethyl-4-(n-propyl)benzene is aminated only at the benzylic position of the ethyl group. The appropriate tuning of salen ligands, especially the aryl substituents at C2, is essential for obtaining high enantio- and regioselectivity. Ir-salen complexes are also efficient catalysts for the intramolecular C-H amination reaction.