Absolute configuration assignment of oxindole derivatives by vibrational circular dichroism exciton coupling

A convenient and reliable approach for the absolute configuration assignment of oxindole derivatives 2a–m by vibrational circular dichroism (VCD) measurements and evaluation of the VCD bisignated couplet resulting from the interaction of the C2 and C9 carbonyl groups is presented. The absolute configuration assignments were further tested by 1H NMR measurements and by X-ray diffraction analysis.

Absolute configuration assignment by vibrational circular dichroism exciton coupling.Figure optionsDownload as PowerPoint slide

2-((R)-1,3-Dimethyl-2-oxoindolin-3-yl)-N-((R)-1-(naphthalen-1-yl)ethyl)acetamideC24H24N2O2Ee >98% (by 1H NMR)[α]D20 = +64.0 (c 1.0, CHCl3)Source of chirality: (R)-(+)-1-(1-naphthyl)-ethylamineAbsolute configuration: (3R,11R)

2-((S)-1,3-Dimethyl-2-oxoindolin-3-yl)-N-((R)-1-(naphthalen-1-yl)ethyl)acetamideC24H24N2O2Ee >98% (by 1H NMR)[α]D20 = +34.7 (c 1.0, CHCl3)Source of chirality: (R)-(+)-1-(1-naphthyl)-ethylamineAbsolute configuration: (3S,11R)

N-((R)-sec-Butyl)-2-((R)-1,3-dimethyl-2-oxoindolin-3-yl)acetamideC16H22N2O2Ee >98% (by 1H NMR)[α]D20 = +23.0 (c 1.0, CHCl3)Source of chirality: (R)-(−)-sec-ButylamineAbsolute configuration: (3R,11R)

N-((R)-sec-Butyl)-2-((S)-1,3-dimethyl-2-oxoindolin-3-yl)acetamideC16H22N2O2Ee >98% (by 1H NMR)[α]D20 = −37.0 (c 1.0, CHCl3)Source of chirality: (R)-(−)-sec-ButylamineAbsolute configuration: (3S,11R)

N-((R)-1-Cyclohexylethyl)-2-((R)-1,3-dimethyl-2-oxoindolin-3-yl)acetamideC20H28N2O2Ee >98% (by 1H NMR)[α]D20 = +48.5 (c 1.0, CHCl3)Source of chirality: (R)-(−)-1-CyclohexylethylamineAbsolute configuration: (3R,11R)

N-((R)-1-Cyclohexylethyl)-2-((S)-1,3-dimethyl-2-oxoindolin-3-yl)acetamideC20H28N2O2Ee >98% (by 1H NMR)[α]D20 = −8.5 (c 1.0, CHCl3)Source of chirality: (R)-(−)-1-CyclohexylethylamineAbsolute configuration: (3S,11R)

2-((R)-1,3-Dimethyl-2-oxoindolin-3-yl)-N-((1R,2R)-2-hydroxycyclohexyl)acetamideC18H24N2O3Ee >98% (by 1H NMR)[α]D20 = +43.3 (c 1.0, CHCl3)Source of chirality: (1R,2R)-trans-2-AminocyclohexanolAbsolute configuration: (3R,11R,12R)

2-((S)-1,3-Dimethyl-2-oxoindolin-3-yl)-N-((1R,2R)-2-hydroxycyclohexyl)acetamideC18H24N2O3Ee >98% (by 1H NMR)[α]D20 = −24.5 (c 1.0, CHCl3)Source of chirality: (1R,2R)-trans-2-AminocyclohexanolAbsolute configuration: (3S,11R,12R)

2-((R)-1,3-Dimethyl-2-oxoindolin-3-yl)-N-((R)-1-hydroxy-3-phenylpropan-2-yl)acetamideC21H24N2O3Ee >98% (by 1H NMR)[α]D20 = +45.8 (c 1.0, CHCl3)Source of chirality: (R)-(+)-2-Amino-3-phenyl-1-propanolAbsolute configuration: (3R,11R)

2-((S)-1,3-Dimethyl-2-oxoindolin-3-yl)-N-((R)-1-hydroxy-3-phenylpropan-2-yl)acetamideC21H24N2O3Ee >98% (by 1H NMR)[α]D20 = +8.5 (c 1.0, CHCl3)Source of chirality: (R)-(+)-2-Amino-3-phenyl-1-propanolAbsolute configuration: (3S,11R)

2-((R)-1,3-Dimethyl-2-oxoindolin-3-yl)-N-(((1S,2R,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)methyl)acetamideC22H30N2O2Ee >98% (by 1H NMR)[α]D20 = +14.5 (c 1.0, CHCl3)Source of chirality: (−)-cis-MyrtanylamineAbsolute configuration: (3R,12R,13S,15S)

2-((S)-1,3-Dimethyl-2-oxoindolin-3-yl)-N-(((1S,2R,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)methyl)acetamideC22H30N2O2Ee >98% (by 1H NMR)[α]D20 = −34.8 (c 1.0, CHCl3)Source of chirality: (−)-cis-MyrtanylamineAbsolute configuration: (3S,12R,13S,15S)

2-((R)-1-Ethyl-3-methyl-2-oxoindolin-3-yl)-N-((R)-1-(naphthalen-1-yl)ethyl)acetamideC25H26N2O2Ee >98% (by 1H NMR)[α]D20 = +62.0 (c 1.0, CHCl3)Source of chirality: (R)-(+)-1-(1-naphthyl)-ethylamineAbsolute configuration: (3R,11R)

2-((S)-1-Ethyl-3-methyl-2-oxoindolin-3-yl)-N-((R)-1-(naphthalen-1-yl)ethyl)acetamideC25H26N2O2Ee >98% (by 1H NMR)[α]D20 = +13.3 (c 1.0, CHCl3)Source of chirality: (R)-(+)-1-(1-naphthyl)-ethylamineAbsolute configuration: (3S,11R)

2-((R)-3-Ethyl-1-methyl-2-oxoindolin-3-yl)-N-((R)-1-(naphthalen-1-yl)ethyl)acetamideC25H26N2O2Ee >98% (by 1H NMR)[α]D20 = +62.8 (c 1.0, CHCl3)Source of chirality: (R)-(+)-1-(1-naphthyl)-ethylamineAbsolute configuration: (3R,11R)

2-((S)-3-Ethyl-1-methyl-2-oxoindolin-3-yl)-N-((R)-1-(naphthalen-1-yl)ethyl)acetamideC25H26N2O2Ee >98% (by 1H NMR)[α]D20 = +30.3 (c 1.0, CHCl3)Source of chirality: (R)-(+)-1-(1-naphthyl)-ethylamineAbsolute configuration: (3S,11R)

(R)-(−)-2-(1,3-Dimethyl-2-oxoindolin-3-yl)acetic acidC12H13N1O3[α]D20 = −15.5 (c 1.0, EtOH)Source of chirality: (R)-(−)-4-Phenyl-2-oxazolidinone in (3R,14R)-7Absolute configuration: (3R)

Methyl (R)-2-(1,3-dimethyl-2-oxoindolin-3-yl)acetateC13H15N1O3[α]D20 = −23.5 (c 1.0, CHCl3)Source of chirality: (R)-(−)-4-Phenyl-2-oxazolidinone in (3R,14R)-7Absolute configuration: (3R)