A C2-symmetric chiral bipyridyldiol–titanium complex as a catalyst for the asymmetric trimethylsilylcyanation of substituted benzaldehydes

This article describes a novel C2-symmetric ligand that comprises a central bipyridine-pinene-derived core and two functionalized two diphenylmethanol subunits. The [8′-(hydroxy-diphenyl-methyl)-10,10,10′,10′-tetramethyl-[5,5′]bi[6-aza-tricyclo[7.1.1.02,7]undecyl]-2(7),3,5,2′(7′),3′,5′-hexane-8-yl]-diphenyl-methanol 1 is an effective catalyst in the enantioselective addition of trimethylsilylcyanide to various aromatic aldehydes with asymmetric inductions of up to 98% ee. Importantly, the correlation between Hammett substituent constants and the enantiomeric excess, and the electron-releasing group at the meta- and para-positions of substituted benzaldehydes were demonstrated to be associated with the high enantioselectivity of the trimethylsilylcyanation reaction that involves trimethylsilylcyanide.

Figure optionsDownload as PowerPoint slide

[8′-(Hydroxy-diphenyl-methyl)-10,10,10′,10′-tetramethyl-[5,5′]bi[6-aza-tricyclo[7.1.1.02,7]undecyl]-2(7),3,5,2′,4′,6′-hexane-8-yl]-diphenyl-methanolC50H48N2O2Ee: 97%[α]D16=-427.5 (c 0.32, CH2Cl2)Source of chirality: (1R)-(+)-α-pineneAbsolute configuration: (1S,1′S,8R,8′R,9S,9′S)

Hydroxy-phenyl-acetonitrileC8H7NO[α]D23.7=-15.0 (c 1.15, CH2Cl2)Absolute configuration: S

Acetoxy-phenyl-acetonitrileC10H9NO2[α]D24.2=-4.3 (c 0.64, CH2Cl2)Absolute configuration: S

Hydroxy-(2-methoxy-phenyl)-acetonitrileC9H9NO2[α]D19=-14.0 (c 1.09, CH2Cl2)Absolute configuration: S

Acetoxy-(2-methoxy-phenyl)-acetonitrileC11H11NO3[α]D24.2=-10.4 (c 0.26, CH2Cl2)Absolute configuration: S

Hydroxy-(3-methoxy-phenyl)-acetonitrileC9H9NO2[α]D24=-14.5 (c 1.41, CH2Cl2)Absolute configuration: S

Acetoxy-(3-methoxy-phenyl)-acetonitrileC11H11NO3[α]D24=-4.1 (c 1.13, CH2Cl2)Absolute configuration: S

Hydroxy-(4-methoxy-phenyl)-acetonitrileC9H9NO2[α]D24=-15.5 (c 1.13, CH2Cl2)Absolute configuration: S

Acetoxy-(4-methoxy-phenyl)-acetonitrileC11H11NO3[α]D24=-3.1 (c 1.10, CH2Cl2)Absolute configuration: S

Hydroxy-o-tolyl-acetonitrileC9H9NO[α]D24.2=-26.7 (c 1.85, CH2Cl2)Absolute configuration: S

Acetoxy-o-tolyl-acetonitrileC11H11NO2[α]D23.7=-17.0 (c 1.54, CH2Cl2)Absolute configuration: S

Hydroxy-m-tolyl-acetonitrileC9H9NO[α]D24.2=-25.8 (c 1.10, CH2Cl2)Absolute configuration: S

Acetoxy-m-tolyl-acetonitrileC11H11NO2[α]D23.6=-3.0 (c 1.20, CH2Cl2)Absolute configuration: S

Hydroxy-p-tolyl-acetonitrileC9H9NO[α]D24.2=-26.3 (c 1.41, CH2Cl2)Absolute configuration: S

Acetoxy-o-p-tolyl- acetonitrileC11H11NO2[α]D23.2=-3.1 (c 1.6, CH2Cl2)Absolute configuration: S

(2-Chloro-phenyl)-hydroxy-acetonitrileC8H6ClNO[α]D19.4=-1.2 (c 2.06, CH2Cl2)Absolute configuration: S

Acetoxy-(2-chloro-phenyl)-acetonitrileC10H8ClNO2[α]D24=-0.9 (c 1.93, CH2Cl2)Absolute configuration: S

(3-Chloro-phenyl)-hydroxy-acetonitrileC8H6ClNO[α]D24.2=-16.7 (c 1.51, CH2Cl2)Absolute configuration: S

Acetoxy-(3-chloro-phenyl)-acetonitrileC10H8ClNO2[α]D23.9=-0.9 (c 0.4, CH2Cl2)Absolute configuration: S

Acetoxy-(4-chloro-phenyl)-acetonitrileC10H8ClNO2[α]D24=-5.6 (c 1.15, CH2Cl2)Absolute configuration: S

3-(Cyano-hydroxy-methyl)-benzonitrileC9H6N2O[α]D22.8=-15.0 (c 1.29, CH2Cl2)Absolute configuration: S

2,2-Dimethylpropioxy-(3-cyano-phenyl)-acetonitrileC11H8N2O2[α]D16=-6.2 (c 1.15, CH2Cl2)Absolute configuration: S

4-(Cyano-hydroxy-methyl)-benzonitrileC9H6N2O[α]D22.6=-3.5 (c 1.48, CH2Cl2)Absolute configuration: S

2,2-Dimethylpropioxy-(4-cyano-phenyl)-acetonitrileC14H14N2O2[α]D22=-0.5 (c 1.15, CH2Cl2)Absolute configuration: S