The synthesis of chiral amino diol tridentate ligands and their enantioselective induction during the addition of diethylzinc to aldehydes

A series of C2-symmetric chiral amino diol tridentate ligands 3a–g were prepared from achiral bulky organolithiums, achiral bulky primary amines, and optically active epichlorohydrin (ECH). The prepared C2-symmetric chiral amino diol tridentate ligands were capable of inducing enantioselectivity in the model reaction of aromatic and aliphatic aldehydes with diethylzinc with an ee of up to 96%. The enantioselectivity can be modulated by adjusting the steric hindrance of the achiral reagents employed in the synthesis of the chiral ligand. The configuration of the addition product depended on the configuration of the amino diol ligands, which can be simply controlled as desired by using the ECH with the desired configuration during the preparation of the ligand.

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Benzyl bis[3-(9-ethylfluoren-9-yl)-2(S)-hydroxypropyl] amineC43H45NO2[α]D20=+106.4 (c 1, THF)Source of chirality: (S)-9-ethylfluoren-9-yl propene oxideAbsolute configuration: (S,S)

Benzyl bis[3-triphenylmethyl-2(R)-hydroxypropyl] amineC51H49NO2[α]D20=+78.8 (c 1, THF)Source of chirality: (R)-4,4,4-triphenylbutene oxideAbsolute configuration: (R,R)

Benzyl bis[3-triphenylmet hyl-2(S)-hydroxypropyl] amineC51H49NO2[α]D20=-78.0 (c 1,THF)Source of chirality: (S)-4,4,4-triphenylbutene oxideAbsolute configuration: (S,S)

n-Butyl bis[3-triphenylmethyl-2(S)-hydroxypropyl] amineC48H51NO2[α]D20=-70.1 (c 1, THF)Source of chirality: (S)-4,4,4-triphenylbutene oxideAbsolute configuration: (S,S)

Benzyl bis[3-(1-pentyldibenzo[a,e]suber-1-yl)-2(S)-hydroxypropyl] amineC53H65NO2[α]D20=+66.8 (c 1, CH2Cl2)Source of chirality: (S)-1-pentyldibenzo[a,e]suber-1-ylpropene oxideAbsolute configuration: (S,S)

Cyclohexyl bis[3-triphenylmethyl-2(S)-hydroxypropyl] amineC50H53NO2[α]D20=-72.6 (c 1, THF)Source of chirality: (S)-4,4,4-triphenylbutene oxideAbsolute configuration: (S,S)

tert-Butyl bis[3-triphenylmethyl-2(S)-hydroxypropyl] amineC48H51NO2[α]D20=-82.55 (c 1, THF)Source of chirality: (S)-4,4,4-triphenylbutene oxideAbsolute configuration: (S,S)

Diphenylmethyl bis[3-triphenylmethyl-2(S)-hydroxypropyl] amineC57H53NO2[α]D20=-69.4 (c 1, THF)Source of chirality: (S)-4,4,4-triphenylbutene oxideAbsolute configuration: (S,S)