α-Pinene-type chiral Schiff bases as tridentate ligands in asymmetric addition reactions

A group of tridentate Schiff bases derived from (+)-α-pinene were synthesized. The steric effects in the transition state, the importance of π–π stacking interactions as well as the electronic effects of aryl aldehydes according to Hammett constant values in the enantioselective addition of Et2Zn to aldehydes with the use of Schiff bases as chiral ligands are described. Also, a variety of aldehydes were cyanated using a catalyst prepared in situ from titanium tetraisopropoxide and chiral Schiff bases. The influence of a conjugated double-bond in the cyanation substrates on enantioselectivity was observed. The chemical structures of the chiral Schiff base–titanium alkoxide complexes are discussed based on their 1H and 13C NMR spectra. 3D models of the Zn2-complex catalyst and Ti-complex catalyst containing α-pinane-type Schiff bases based on X-ray diffraction experiments are postulated. The models presented were consistent with the reported chirality of the addition product and observed ee.

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2-((E)-((1S,2S,3R,5S)-3-(Hydroxymethyl)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ylimino)-methyl)phenolC18H25NO2Ee ⩾ 97%[α]D20=+70.8 (c 0.048, CH3OH)Source of chirality: (+)-α-pineneAbsolute configuration: (E)-(1S,2S,3R,5S)

2-((E)-((1S,2S,3R,5S)-3-(Hydroxymethyl)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ylimino)methyl)-6-methylphenolC19H27NO2Ee ⩾ 97%[α]D20=+63.0 (c 0.268, CH3OH)Source of chirality: (+)-α-pineneAbsolute configuration: (E)-(1S,2S,3R,5S)

2-tert-Butyl-6-((E)-((1S,2S,3R,5S)-3-(hydroxymethyl)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ylimino)methyl)-4-methylphenolC23H35NO2Ee ⩾ 97%[α]D20=-4.9 (c 0.41, CH3OH)Source of chirality: (+)-α-pineneAbsolute configuration: (E)-(1S,2S,3R,5S)

2,4-Di-tert-butyl-6-((E)-((1S,2S,3R,5S)-3-(hydroxymethyl)-2,6,6-trimethylbicyclo[3.1.1]-heptan-2-ylimino)methyl)phenolC26H41NO2Ee ⩾ 97%[α]D20=+37.5 (c 0.044, CH3OH)Source of chirality: (+)-α-pineneAbsolute configuration: (E)-(1S,2S,3R,5S)

4-Bromo-2-((E)-((1S,2S,3R,5S)-3-(hydroxymethyl)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ylimino)methyl)phenolC18H24BrNO2Ee ⩾ 97%[α]D20=+51.5 (c 0.466, CH3OH)Source of chirality: (+)-α-pineneAbsolute configuration: (E)-(1S,2S,3R,5S)

5-(Diethylamino)-2-((E)-((1S,2S,3R,5S)-3-(hydroxymethyl)-2,6,6-trimethylbicyclo[3.1.1]-heptan-2-ylimino)methyl)phenolC22H34N2O2Ee ⩾ 97%[α]D20=+92.1 (c 0.038, CH3OH)Source of chirality: (+)-α-pineneAbsolute configuration: (E)-(1S,2S,3R,5S)