Catalytic asymmetric difunctionalization of alkenes: Aminohalogenation and aminooxygenation
Kim, Jin Woo
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Vicinal haloamines as versatile synthetic intermediates in organic synthesis and nitrogen-containing heterocycles are very important compounds. Vicinal haloamines can play a role as a motif to synthesize biologically important compounds such as amino acid, amino aldehyde, lactam and lactones. Also, a lot of medicinal agents and natural products have nitrogen-containing hetercycles. These two compounds can be produced from aminohalogenation. Palladium catalytic aminohalogenation developed by our group has showed already promising results with modest to high yield and regioselectivity. However, little was reported so far on catalytic, asymmetric aminohalogenation of olefins. Preliminary study on enantioselective aminohalogenation with some chiral ligands showed the asymmetric induction in spite of low enantioselectivity. Herein were other commercially available chiral ligands investigated to find out a suitable ligand for our aminohalogenation. Also, alternative halogen sources in addition to copper halide and other bases besides K 2 CO 3 were studied. Vicinal amino alcohols are useful intermediates in organic synthesis in regard that various medicinal drugs and natural products contain amino alcohols. When the reaction mechanism of copper catalytic carboamination developed by our group was studied, it was discovered the carbon radical species could be formed during carboamination and it could react faster with TEMPO, radical trapping agent than another carbon on benzene ring of tosyl functional group. This investigative work initiated the development of aminooxygenation. Since sharpless aminohydroxylation was developed, although many works on asymmetric intermolecular AH or diastereoselective intramolecular AH reaction have been reported, asymmetric AH reaction has not been studied yet. In this chapter for the first enantioselective aminooxygenation, for asymmetric induction, promising chiral ligands were screened and other reaction conditions such as reaction temperature, solvent were optimized. Under the optimized reaction condition, various aryl and aliphatic substrates were studied to investigate enantioselectivity as well as yield. TEMPO adduct were reduced or oxidized to alcohol or aldehyde, respectively to show enantioselectivity is not diminished. Also, the optical rotation of alcohol reduced from TEMPO adduct was compared to that of the known alcohol. In our catalytic asymmetric aminooxygenation, TEMPO which has been commonly used for radical trapping is re-highlighted as an important tool for aminooxygenation.