Design and synthesis of chiral hybrid spiro (isoxazole–isoxazoline) ligands

Novel chiral hybrid ligands containing an unsymmetrical spiro[4.5]decane skeleton with isoxazole and isoxazoline as the two coordinating units have been synthesized. Pd complexes of these ligands were found to be effective in activating olefins towards enantioselective tandem cyclization of a dialkenyl alcohol, providing the cyclized products in up to 97% ee.

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(R∗,S∗)-3′,3a′,4′,5,5′,6-Hexahydro-4H-spiro[2,1-benzisoxazole-7,6′-cyclopenta[c]isoxazole]C12H14N2O2Ee = >99%[α]D29=-134 (c 0.11, CHCl3)Relative configuration: (R∗,S∗)

(R∗,S∗)-3,3′-Diethyl-3′,3a′,4′,5,5′,6-hexahydro-4H-spiro[2,1-benzisoxazole-7,6′-cyclopenta[c]isoxazole]C16H22N2O2Ee = >99%[α]D29=-186 (c 0.10, CHCl3)Relative configuration: (R∗,S∗)

(R∗,S∗)-3,3′,3′-Trimethyl-3′,3a′,4′,5,5′,6-hexahydro-4H-spiro[2,1-benzisoxazole-7,6′-cyclopenta[c]isoxazole]C15H20N2O2Ee = >99%[α]D29=-202 (c 0.10, CHCl3)Relative configuration: (R∗,S∗)

(R∗,S∗)-3′,3′-Diisopropyl-3′,3a′,4′,5,5′,6-hexahydro-4H-spiro[2,1-benzisoxazole-7,6′-cyclopenta[c]isoxazole]C18H26N2O2Ee = >99%[α]D29=-178 (c 0.11, CHCl3)Relative configuration: (R∗,S∗)

(R∗,S∗)-3-tert-Butyl-3′,3′-diisopropyl-3′,3a′,4′,5,5′,6-hexahydro-4H-spiro[2,1-benzisoxazole-7,6′-cyclopenta[c]isoxazole]C22H34N2O2Ee = >99%[α]D29=-114 (c 0.10, CHCl3)Relative configuration: (R∗,S∗)