Discovery of chiral catalysts by asymmetric activation for highly enantioselective diethylzinc addition to imines: using racemic and achiral diimines as effective activators

A library of chiral zinc complexes formed in situ by the combination of achiral and racemic diimines with 3,3′-di(3,5-ditrifluoromethylphenyl)-BINOL and diethylzinc were evaluated in the asymmetric addition of diethylzinc to N-acylimines. In the presence of 10 mol % of chiral ligand 4 and racemic diimine 5, high enantioselectivities of up to 97% ee and yields of up to 96% were achieved for a wide range of aromatic imines in dichloromethane at −30 °C.

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N-[1-(4-Bromophenyl)propyl]formamideC10H12BrNOEe = 96%[α]D20=+144.3 (c 0.26, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

N-[1-(3-Bromophenyl)propyl]formamideC10H12BrNOEe = 97%[α]D20=+109.8 (c 1.33, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

N-[1-(3-Chlorophenyl)propyl]formamideC10H12ClNOEe = 95%[α]D20=+114.8 (c 1.46, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

N-(1-Phenylpropyl)formamideC10H13NOEe = 88%[α]D20=+126.2 (c 0.48, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

N-[1-(4-Chlorophenyl)propyl]formamideC10H12ClNOEe = 94%[α]D20=+130.6 (c 0.68, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

N-[1-p-Tolypropyl]formamideC11H15NOEe = 91%[α]D20=+122.3 (c 0.54, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

N-[1-(4-Methoxyphenyl)propyl]formamideC11H15NO2Ee = 90%[α]D20=+132.6 (c 0.39, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

N-[1-(4-Cyanophenyl)propyl]formamideC11H12N2OEe = 92%[α]D20=+49.3 (c 1.75, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

N-[1-(4-(Trifluoro)phenyl)propyl]formamideC11H12F3NOEe = 94%[α]D20=+91.5 (c 0.82, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

4-(1-Formylaminopropyl)benzoic acid methyl esterC12H15NO3Ee = 93%[α]D20=+41.0 (c 0.57, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R