Synthesis of novel chiral oxazoline ligands and application in the highly enantioselective diethylzinc addition to N-diphenylphosphinoylimines

Two sets of novel chiral oxazoline ligands were designed and conveniently prepared from readily available l-aspartic acid and evaluated in enantioselective diethylzinc addition to N-diphenylphosphinoyl imines. In the presence of stoichiometric amounts of these ligands, high enantioselectivities (up to 95% ee) and yields (up to 85%) were achieved for several aromatic imines in toluene at room temperature. Furthermore, the effect of the structure of the ligand on the reaction was studied.

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(R)-1-Phenyl-2-((S)-2-phenyl-4,5-dihydrooxazol-4-yl)ethanolC17H17NO2[α]D20=+79.3 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (R,S)

(S)-1-Phenyl-2-((S)-2-phenyl-4,5-dihydrooxazol-4-yl)ethanolC17H17NO2[α]D20=-142.0 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

(R)-2-((S)-2-(4-Fluorophenyl)-4,5-dihydrooxazol-4-yl)-1-phenylethanolC17H16FNO2[α]D20=+75.3 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (R,S)

(S)-2-((S)-2-(4-Fluorophenyl)-4,5-dihydrooxazol-4-yl)-1-phenylethanolC17H16FNO2[α]D20=-148.7 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

(R)-2-((S)-2-(4-Chlorophenyl)-4,5-dihydrooxazol-4-yl)-1-phenylethanolC17H16ClNO2[α]D20=+82.0 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (R,S)

(S)-2-((S)-2-(4-Chlorophenyl)-4,5-dihydrooxazol-4-yl)-1-phenylethanolC17H16ClNO2[α]D20=-154.0 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

(R)-2-((S)-2-(4-Bromophenyl)-4,5-dihydrooxazol-4-yl)-1-phenylethanolC17H16BrNO2[α]D20=+67.0 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (R,S)

(S)-2-((S)-2-(4-Bromophenyl)-4,5-dihydrooxazol-4-yl)-1-phenylethanolC17H16BrNO2[α]D20=-142.7 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)

(R)-2-((S)-2-(Naphthalen-1-yl)-4,5-dihydrooxazol-4-yl)-1-phenylethanolC21H19NO2[α]D20=+131.7 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (R,S)

(S)-2-((S)-2-(Naphthalen-1-yl)-4,5-dihydrooxazol-4-yl)-1-phenylethanolC21H19NO2[α]D20=-82.7 (c 0.3, CH2Cl2)Source of chirality: l-aspartic acidAbsolute configuration: (S,S)