Design and synthesis of the first spiro bis(isoxazoline) derivatives as asymmetric ligands

[GRAPHICS] A chiral bis(isoxazoline) ligand (SPRIX) containing a rigid spiro skeleton was designed and synthesized via a double intramolecular nitrile oxide cycloaddition, The optically pure SPRIX greatly accelerated the Cu(acac)(2)-catalyzed asymmetric reaction of diisopropylzinc with cyclohexenone to give the Michael adduct with 49% ee. This is the first example of the use of an isoxazoline ligand for a transition metal catalyzed reaction. The X-ray crystallographic analysis of the hexacoordinated copper complex of SPRIX confirmed the ligand character.