Synthesis of novel chiral tridentate aminophenol ligands for enantioselective addition of diethylzinc to aldehydes

Novel chiral tridentate aminophenol ligand (S)-3a was obtained by a Mannich-type reaction of cresol, paraformaldehyde, and (S)-1-(2-methoxyphenyl)-2-methylpropan-1-amine followed by a deprotection step. This tridentate aminophenol ligand shows high yield and enantioselectivity in the diethylzinc additions to a broad range of substrates, including alkyl, aryl, and α,β-unsaturated aldehydes.

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2-(((S)-1-(2-Methoxyphenyl)-2-methylpropylamino)methyl)-4-methylphenolC19H25NO2Ee >99%[α]D23=-18.6 (c 0.582, CHCl3)Source of chirality: (S)-1-(2-methoxyphenyl)-2-methylpropan-1-amineAbsolute configuration: (S)

2-(((S)-1-(2-Methoxyphenyl)-2,2-dimethylpropylamino)methyl)-4-methylphenolC20H27NO2Ee >99%[α]D23=+6.6 (c 0.696, CHCl3)Source of chirality: (S)-1-(2-methoxyphenyl)-2,2-dimethylpropan-1-amineAbsolute configuration: (S)

2-((S)-1-(2-Hydroxy-5-methylbenzylamino)-2-methylpropyl)phenolC18H23NO2Ee >99%[α]D23=-19.0 (c 0.400, CHCl3)Source of chirality: (S)-1-(2-methoxyphenyl)-2-methylpropan-1-amineAbsolute configuration: (S)

2-((S)-1-(2-Hydroxy-5-methylbenzylamino)-2,2-dimethylpropyl)phenolC19H25NO2Ee >99%[α]D23=-22.5 (c 0.516, CHCl3)Source of chirality: (S)-1-(2-methoxyphenyl)-2,2-dimethylpropan-1-amineAbsolute configuration: (S)