Synthesis of novel chiral 1,3-aminophenols and application for the enantioselective addition of diethylzinc to aldehydes

Novel chiral 1,3-aminophenols were efficiently synthesized by applying a Friedel–Crafts reaction and optical resolution. The catalytic activity of the aminophenols was studied for the addition of diethylzinc to benzaldehyde. The results showed that (S)-5a with bulky tert-butyl groups on the stereogenic carbon atom and 4,6-positions of phenol favored higher enantioselectivity (94% ee). The same ligand was also used with other aldehydes, to give optically active alcohols in good chemical yields and ee values (up to 99%).

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2-((R)-1-Amino-2-phenylethyl)-4-methylphenolC15H17NOEe >99%[α]D20=-48.0 (c 0.5, MeOH)Source of chirality: optical resolutionAbsolute configuration: (R)

(−)-2-(1-Aminoethyl)-4-methylphenolC9H13NOEe >99%[α]D20=-16.2 (c 0.5, 0.1 M HCl (aq))Source of chirality: optical resolution

(S)-2-(1-Amino-2,2-dimethylpropyl)-4-tert-butylphenolC15H25NOEe >99%[α]D20=-6.8 (c 0.326, diethyl ether)Source of chirality: (S)-2-(1-amino-2,2-dimethylpropyl)phenolAbsolute configuration: (S)

(S)-2-(1-Amino-2-methylpropyl)-4-tert-butylphenolC14H23NOEe >99%[α]D20=-13.9 (c 0.36, CHCl3)Source of chirality: (S)-2-(1-amino-2-methylpropyl)phenolAbsolute configuration: (S)

(S)-2-(1-Amino-2,2-dimethylpropyl)-4,6-di-tert-butylphenolC19H33NOEe >99%[α]D20=+22.0 (c 0.5, CH3COOCH2CH3)Source of chirality: (S)-2-(1-amino-2,2-dimethylpropyl)phenolAbsolute configuration: (S)

(S)-2-(1-Amino-2-methylpropyl)-4,6-di-tert-butylphenolC18H31NOEe >99%[α]D20=+5.8 (c 0.584, diethyl ether)Source of chirality: (S)-2-(1-amino-2-methylpropyl)phenolAbsolute configuration: (S)

(R)-2-(1-Amino-2-phenylethyl)-6-tert-butyl-4-methylphenolC19H25NOEe >99%[α]D20=-26.1 (c 1.8, CHCl3)Source of chirality: 2-((R)-1-amino-2-phenylethyl)-4-methylphenolAbsolute configuration: (R)

(−)-2-(1-Aminoethyl)-6-tert-butyl-4-methylphenolC13H21NOEe >99%[α]D20=-21.2 (c 0.6, CHCl3)Source of chirality: (−)-2-(1-aminoethyl)-4-methylphenol