O-Methylatrolactic acid as a new reagent for determination of the enantiomeric purity and absolute configuration of chiral alcohols and amines

Easily available in both enantiomeric forms, O-methylatrolactic acid (MAA) was successfully used as a new chiral derivatizing agent. Enantiomeric purities and the absolute configurations of chiral secondary alcohols and amines were determined using the observed differences in 1H NMR chemical shifts. The Mosher’s stereochemical model explains the conformational preferences of the respective diastereomeric MAA esters and amides. This was confirmed by the results of DFT calculations for the respective conformers.

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(S)-2-((S)-2-Methoxy-2-phenyl-propionylamino)-4-methyl-pentanoic acid methyl esterC17H25NO4De = 100%[α]D20=+12.7 (c 0.88, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2S,2′S)

(2S,3S)-2-((S)-2-Methoxy-2-phenyl-propionylamino)-3-methyl-pentanoic acid methyl esterC17H25NO4De = 100%[α]D20=+35.8 (c 0.30, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2S,2′S,3′S)

(S)-2-((S)-2-Methoxy-2-phenyl-propionylamino)-4-methylsulfanyl-butyric acid methyl esterC16H23NO4SDe = 100%[α]D20=+36.4 (c 0.84, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2S,2′S)

(S)-2-((S)-2-Methoxy-2-phenyl-propionylamino)-3-phenyl-propionic acid methyl esterC20H23NO4De = 100%[α]D20=+98.7 (c 1.14, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2S,2′S)

(S)-3-(1H-Indol-3-yl)-2-((S)-2-Methoxy-2-phenyl-propionylamino)-propionic acid methyl esterC22H24N2O4De = 100%[α]D20=+75.6 (c 0.24, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2S,2′S)

(S)-2-Methoxy-2-phenyl-N-((R)-1-phenyl-ethyl)-propionamideC18H21NO2De = 100%[α]D20=+130.3 (c 0.26, CH2Cl2)Absolute configuration: (2S,2′R)

(R)-2-Aminopropanol-(R)-O-methylatrolactic acid amideC13H19NO3De = 100%[α]D20=-39.7 (c 1.36, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2R,2′R)

(S)-Phenylalanin-2-ol-(R)-O-methylatrolactic acid amideC19H23NO3De = 100%[α]D20=-43.0 (c 0.64, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2R,2′S)

(−)-Ephedrine-(R)-O-methylatrolactic acid amideC20H25NO3De = 100%[α]D20=+3.4 (c 0.76, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2R,1′S,2′R)

(R)-Propan-2-ol-O-methylatrolactateC13H18O3Ee >98%[α]D20=+24.4 (c 0.31, CH2Cl2)Source of chirality: O-methylatrolactic acidAbsolute configuration: (R)

(R,S)-sec-Butyl-O-methylatrolactateC14H20O3De = 100%[α]D20=+40.4 (c 0.76, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (1R,2′S)

(−)-Bornyl-(S)-O-methylatrolactateC20H28O3De = 100%[α]D20=-37.9 (c 0.83, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2S,2′S)

(−)-Menthyl (R)-O-methylatrolactateC20H30O3De = 100%[α]D20=-49.5 (c 1.1, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2R,1′R,2′S,3′R)

(−)-Bornyl (R)-O-methylatrolactateC20H28O3De = 100%[α]D20=-11.1 (c 0.92, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2R,2′S)

(−)-cis-Caran-trans-4-yl (R)-O-methylatrolactateC20H28O3De = 100%[α]D20=-42.3 (c 1.0, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2R,1′R,2′R,3′S,4′R)

(−)-Menthyl (S)-O-methylatrolactateC20H30O3De = 100%[α]D20=-73.3 (c 0.63, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (2S,1′R,2′S,3′R)

(−)-cis-Caran-trans-4-yl (S)-O-methylatrolactateC20H28O3De = 100%[α]D20=-74.2 (c 0.90, CH2Cl2)Source of chirality: natural compoundsAbsolute configuration: (1S,1′R,2′R,4′S,5′R)

(S)-1-Phenylethyl-(S)-O-methylatrolactateC18H20O3De = 100%[α]D20=-44.2 (c 0.75, CH2Cl2)Absolute configuration: (2S,2′S)

(S)-2-Methoxy-2-phenyl-propionic acid (S)-methoxycarbonyl-phenyl-methyl esterC19H20O5De = 100%[α]D20=+61.3 (c 1.05, CH2Cl2)Absolute configuration: (2S,2′S)