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)

An efficient catalytic system comprising of chiral C1-tetrahydro-1,1′-bisisoquinoline and CuCl in the ratio of 2:1 has been developed for the enantioselective Henry reaction. The catalytic efficiencies of the chiral C1-tetrahydro-1,1′-bisisoquinolines are governed to a great extent by the structural constraints and the type of substituent on the sp3-N. Aromatic and aliphatic aldehydes reacted with nitromethane to give β-nitroalcohols in very high yields (up to 95%) and enantioselectivities (up to 91% ee). The present catalyst system is simple in operation since no special precautions were taken to exclude moisture or air from the reaction flask and no additives were required for activation. Nonlinear effects have also been studied for this reaction.(R)-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC18H16N2[α]D20=+202.0 (c 0.9, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (R)