Synthesis of planar chiral [2.2]paracyclophane Schiff bases for the enantioselective Henry reaction

A series of diastereomerically pure Schiff base ligands based on [2.2]paracyclophane backbones were synthesized and separated. The new planar chiral [2.2]paracyclophane Schiff bases were used as ligands in Cu-catalyzed asymmetric Henry reactions with high yields and enantioselectivities.

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(Sp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-fluoro-[2.2]paracyclophaneC24H30FNO2[α]D20=+655.0 (c 0.10, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Sp,S)

(Rp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-fluoro-[2.2]paracyclophaneC24H30FNO2[α]D20=-280 (c 0.10, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Rp,S)

(Sp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-iodo-[2.2]paracyclophaneC24H30INO2[α]D20=+756.0 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Sp,S)

(Rp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-iodo-[2.2]paracyclophaneC24H30INO2[α]D20=-431.8 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Rp,S)

(Sp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-methoxy-[2.2]paracyclophaneC25H33NO3[α]D20=+964.0 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Sp,S)

(Rp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-methoxy-[2.2]paracyclophaneC25H33NO3[α]D20=-613.1 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Rp,S)

(Rp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-(2,3-dimethoxyphenyl)-[2.2]paracyclophaneC32H39NO4[α]D20=+434.1 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Rp,S)