A series of new planar and central chiral ligands based on [2.2]paracyclophane backbones were designed and prepared from enantiomerically pure 4-amino-13-bromo[2.2]paracyclophane and commercially available chiral amino alcohols. Their application in a copper-catalyzed asymmetric Henry reaction resulted in secondary alcohols with high yield and excellent selectivity for active aldehydes (up to 94% ee). This is a successful example of employing planar chiral [2.2]paracyclophane ligands in copper-catalyzed reaction.Schiff base of (4Sp,5Rp,13Rp)-5-acetyl-13-bromo-4-hydroxy-[2.2]paracyclophane and benzylamineC25H24BrNO[α]D20=-19.6 (c 0.40, CH2Cl2)Source of chirality: (4Sp,13Rp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (4Sp,5Rp,13Rp)Schiff base of (4Sp,5Rp,13Rp)-5-acetyl-13-bromo-4-hydroxy-[2.2]paracyclophane and (R)-2-phenylglycinolC26H26BrNO2[α]D20=-195.1 (c 0.50, CH2Cl2)Source of chirality: (4Sp,13Rp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (R,4Sp,5Rp,13Rp)Schiff base of (4Sp,5Rp,13Rp)-5-acetyl-13-bromo-4-hydroxy-[2.2]paracyclophane and (S)-tert-leucinolC24H30BrNO2[α]D20=-415.5 (c 0.20, CH2Cl2)Source of chirality: (4Sp,13Rp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (S,4Sp,5Rp,13Rp)Schiff base of (4Sp,5Rp,13Rp)-5-benzoyl-13-bromo-4-hydroxy-[2.2]paracyclophane and (R)-2-phenylglycinolC31H28BrNO2[α]D20=-265.5 (c 0.20, CH2Cl2)Source of chirality: (4Sp,13Rp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (R,4Sp,5Rp,13Rp)Schiff base of (4Rp,5Sp,13Sp)-5-acetyl-13-bromo-4-hydroxy-[2.2]paracyclophane and (S)-tert-leucinolC24H30BrNO2[α]D20=+817.8 (c 0.20, CH2Cl2)Source of chirality: (4Rp,13Sp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (S,4Rp,5Sp,13Sp)Schiff base of (4Rp,5Sp,13Sp)-5-acetyl-4-hydroxy-13-(3-meth-oxylphenyl)[2.2]paracyclophane and (S)-tert-leucinolC31H37NO3[α]D20=+567.5 (c 0.20, CH2Cl2)Source of chirality: (4Rp,13Sp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (S,4Rp,5Sp,13Sp)

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.(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)