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)

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 cyclopropane-based bisoxazolines were synthesized from (R)- and (S)-amino alcohols, and applied to copper-catalyzed enantioselective nitroaldol reactions between nitromethane and various aldehydes. The reactions generated β-hydroxy nitroalkanes in high yields (97%) and with good enantioselectivities (up to 87% ee). The effects of the oxazoline stereocenters constructed in the Henry reactions were also studied.(1R,2S)-1,2-Bis[4(S)-isopropyloxazolin-2-yl]-3,3-dimethylcyclopropaneC17H28N2O2[α]D20=-131.3 (c 1.6, CHCl3)Source of chirality: (S)-valinol(1R,2S)-1,2-Bis [4(S)-tert-butyloxazolin-2-yl]-3,3-dimethylcyclopropaneC19H32N2O2[α]D20=-135.8 (c 2.1, CHCl3)Source of chirality: (S)-tert-leucinol(1R,2S)-1,2-Bis[4(S)-benzyloxazolin-2-yl]-3,3-dimethylcyclopropaneC25H28N2O2[α]D20=-56.5 (c 0.78, CHCl3)Source of chirality: (S)-phenylalaninol(1R,2S)-1,2-Bis[4(R)-phenyloxazolin-2-yl]-3,3-dimethylcyclopropaneC23H24N2O2[α]D25=+160.2 (c 1.5, CHCl3)Source of chirality: (R)-phenylglycinol(1R,2S)-1,2-Bis[4(S)-phenyloxazolin-2-yl]-3,3-dimethylcyclopropaneC23H24N2O2[α]D20=-152.3 (c 2.0, CHCl3)Source of chirality: (S)-phenylglycinolAbsolute configuration: (1R,2S)(1R,2S)-1,2-Bis[4(R)-phenyloxazolin-2-yl]-3,3-dimethylcyclopropaneC17H28N2O2[α]D25=+126.5 (c 2.4, CHCl3)Source of chirality: (R)-phenylglycinolAbsolute configuration: (1R,2S)