Structural and electronic effects of oxazolidine ligands derived from (1R,2S)-ephedrine in the asymmetric addition of diethylzinc to aldehydes

The purpose of this research was to determine the activity of chiral oxazolidine ligands prepared from (1R,2S)-ephedrine for the enantioselective addition of diethylzinc to aldehydes. The configuration on the newly formed C2 stereogenic center was determined as (2S) by X-ray structural analysis. Oxazolidine ligands reveal medium enantioselectivity with the ee exceeding 57%, and the yields obtained being 68–99%. The results indicate that the absolute configuration of the addition product depends not only on the N3-methyl as an important stereocontrol element but also on both the electronic and steric effects of the substrates and oxazolidine ligands.

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4-Bromo-2-((2S,4S,5R)-3,4-dimethyl-5-phenyloxazolidin-2-yl)phenolC17H18BrNO2Ee = 99%[α]D20=-79.2 (c 0.096, CH3OH)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (2S,4S,5R)

2-((2S,4S,5R)-3,4-Dimethyl-5-phenyloxazolidin-2-yl)-6-methylphenolC18H21NO2Ee = 99%[α]D20=+8.2 (c 0.56, CH3OH)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (2S,4S,5R)

2-((2S,4S,5R)-3,4-Dimethyl-5-phenyloxazolidin-2-yl)-6-isopropylphenolC20H25NO2Ee = 99%[α]D20=+5.0 (c 2.09, CH3OH)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (2S,4S,5R)

2-tert-Butyl-6-((2S,4S,5R)-3,4-dimethyl-5-phenyloxazolidin-2-yl)-4-methylphenolC22H29NO2Ee = 99%[α]D20=-7.2 (c 0.40, CH3OH)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (2S,4S,5R)

2,4-Di-tert-butyl-6-((2S,4S,5R)-3,4-dimethyl-5-phenyloxazolidin-2-yl)phenolC25H35NO2Ee = 99%[α]D20=-27.85 (c 0.406, CH3OH)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (2S,4S,5R)

1-((2S,4S,5R)-3,4-Dimethyl-5-phenyloxazolidin-2-yl)naphthalen-2-olC21H21NO2Ee = 99%[α]D20=-8.4 (c 0.16, CH3OH)Source of chirality: (1R,2S)-ephedrineAbsolute configuration: (2S,4S,5R)