Abstract
Background: The asymmetric Michael-Henry cascade reaction of 1,2-dione with nitroolefins is an important method for the preparation of chiral bicycle[3,2,1] octane derivatives, which are useful intermediates for the synthesis of biologically active bicyclo octane skeletal compounds. However, limited success has been achieved so far for ionic liquid supported (ILS) chiral ligands in transition metal catalyzed asymmetric cascade reactions.
Methods: The catalyst was generated in situ by the combination of ammonium ILS diamine 6b ligand (3 mol%) with metal salt Ni(OAc)2 (3 mol%) in a solvent dimethylformamide. Then the substrates 1,2- cyclohexadione and nitroolefin were added and the reaction mixture was stirred at room temperature for 0.3-2.7 h.
Results: The ammonium ILS diamines were successfully utilized as chiral ligands in Ni(II)-catalyzed asymmetric Michael-Henry cascade reactions between 1,2-cyclohexadione and nitroolefins at room temperature. High yields (80-98%), high diastereoselectivities (up to 47:1) and enantioselectivities (84- 94% ee) were observed for the various bicyclo [3,2,1] octane derivatives containing many functional groups.
Conclusion: 1,2-cyclohexadione underwent asymmetric Michael-Henry cascade reaction with nitroolefins in the presence of ammonium ILS diamine/Ni(II) catalyst to give the bicyclo [3,2,1] octane derivatives in high yields with ee ranging from 84-94%. Furthermore, the catalytic system is recyclable.
Keywords: Ionic liquid, cyclohexanediamine, enantioselectivity, cascade Michael-Henry reaction, Ni(II)-complex, nitroolefin.
Graphical Abstract
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