| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1347910 | Tetrahedron: Asymmetry | 2012 | 15 Pages |
Herein we describe a straightforward method for the determination of the absolute configuration of 3-indolyl(bromo)acetate 7, 3-indolyl(alkoxy)acetates 8a–f and 3-indolyl(amino)acetate 8g, based on 1H NMR spectral analysis. The conformational preferences for two diastereomeric esters were calculated by DFT, which matched very well with the experimental results. X-ray diffraction analysis allowed us to validate the methodology, and independent absolute configuration evidence was obtained by vibrational circular dichroism.
Graphical abstractAbsolute configuration assignment by 1H NMR and VCD.Figure optionsDownload full-size imageDownload as PowerPoint slide
(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(1H-indol-3-yl)acetateC20H27NO2ee >98% (by 1H NMR)[α]D20=-68.8 (c 1.6, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (10R,11S,14R)
(R)-sec-Butyl 2-(1H-indol-3-yl)acetateC14H17NO2ee >98% (by 1H NMR)[α]D20=-13.3 (c 0.60, EtOH)Source of chirality: (R)-(−)-2-ButanolAbsolute configuration: (10R)
Methyl 3-(2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-1H-indole-1-carboxylateC22H29NO4ee >98% (by 1H NMR)[α]D20=-51.9 (c 1.5, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (10R,11S,14R)
(R)-Methyl 3-(2-sec-butoxy-2-oxoethyl)-1H-indole-1-carboxylateC16H19NO4ee >98% (by 1H NMR)[α]D20=-18.3 (c 1.2, EtOH)Source of chirality: (R)-(−)-2-ButanolAbsolute configuration: (10R)
tert-Butyl 3-(2-((1R,2R,5S)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-1H-indole-1-carboxylateC25H35NO4ee > 98% (by 1H NMR)[α]D20=-40.8 (c 1.2, EtOH)Source of chirality: (1R,2S,5R)-(-)-MentholAbsolute configuration: (10R,11S,14R)
Methyl 2,6-dibromo-3-((S)-1-bromo-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-1H-indole-1-carboxylateC22H26Br3NO4ee >98% (by 1H NMR)[α]D20=-5.0 (c 0.5, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8S,10R,11S,14R)
Methyl 2,6-dibromo-3-((R)-1-bromo-2-((1R,2R,5S)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-1H-indole-1-carboxylateC22H26Br3NO4ee >98% (by 1H NMR)[α]D20=-2.0 (c 0.6, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8R,10R,11S,14R)
Methyl 3-((S)-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-1-methoxy-2-oxoethyl)-1H-indole-1-carboxylateC23H31NO5ee >98% (by 1H NMR)[α]D20=-16.0 (c 1.3, EtOH)Source of chirality: (1R,2S,5R)-(-)-MentholAbsolute configuration: (8S,10R,11S,14R)
Methyl 3-((R)-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-1-methoxy-2-oxoethyl)-1H-indole-1-carboxylateC23H31NO5ee > 98% (by 1H NMR)[α]D20=-102.9 (c 1.6, EtOH)Source of chirality: (1R,2S,5R)-(-)-MentholAbsolute configuration: (8R,10R,11S,14R)
Methyl 3-((S)-1-ethoxy-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-1H-indole-1-carboxylateC24H33NO5ee >98% (by 1H NMR)[α]D20=-18.9 (c 1.6, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8S,10R,11S,14R)
Methyl 3-((R)-1-ethoxy-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-1H-indole-1-carboxylateC24H33NO5ee >98% (by 1H NMR)[α]D20=-70.8 (c 1.2, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8R,10R,11S,14R)
Methyl 3-((S)-1-isopropoxy-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-1H-indole-1-carboxylateC25H35NO5ee >98% (by 1H NMR)[α]D20=-14.8 (c 2.2, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8S,10R,11S,14R)
Methyl 3-((R)-1-isopropoxy-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-2-oxoethyl)-1H-indole-1-carboxylateC25H35NO5ee >98% (by 1H NMR)[α]D20=-83.2 (c 2.5, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8R,10R,11S,14R)
Methyl 3-((S)-2-sec-butoxy-1-methoxy-2-oxoethyl)-1H-indole-1-carboxylateC17H21NO5ee >98% (by 1H NMR)[α]D20=+41.3 (c 0.8, EtOH)Source of chirality: (R)-(−)-2-ButanolAbsolute configuration: (8S,10R)
Methyl 3-((R)-2-sec-butoxy-1-methoxy-2-oxoethyl)-1H-indole-1-carboxylateC17H21NO5ee >98% (by 1H NMR)[α]D20=-51.7 (c 1.2, EtOH)Source of chirality: (R)-(−)-2-ButanolAbsolute configuration: (8R,10R)
tert-Butyl 3-((S)-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-1-methoxy-2-oxoethyl)-1H-indole-1-carboxylateC26H37NO5ee > 98% (by 1H NMR)[α]D20=-12.5 (c = 1.2, EtOH).Source of chirality: (1R,2S,5R)-(-)-MentholAbsolute configuration: (8S,10R,11S,14R)
tert-Butyl 3-((R)-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-1-methoxy-2-oxoethyl)-1H-indole-1-carboxylateC26H37NO5ee >98% (by 1H NMR)[α]D20=-88.75 (c 0.8, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8R,10R,11S,14R)
Methyl 2,6-dibromo-3-((S)-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-1-methoxy-2-oxoethyl)-1H-indole-1-carboxylateC23H29Br2NO5ee > 98% (by 1H NMR)[α]D20=-96.1 (c 0.8, EtOH)Source of chirality: (1R,2S,5R)-(-)-MentholAbsolute configuration: (8S,10R,11S,14R)
Methyl 2,6-dibromo-3-((R)-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-1-methoxy-2-oxoethyl)-1H-indole-1-carboxylateC23H29Br2NO5ee >98% (by 1H NMR)[α]D20=-5.0 (c 0.8, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8R,10R,11S,14R)
Methyl 3-((S)-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-1-(methylamino)-2-oxoethyl)-1H-indole-1-carboxylateC23H32N2O4ee >98% (by 1H NMR)[α]D20=-10.9 (c 1.27, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8S,10R,11S,14R)
Methyl 3-((R)-2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-1-(methylamino)-2-oxoethyl)-1H-indole-1-carboxylateC23H32N2O4ee >98% (by 1H NMR)[α]D20=-87.0 (c 1.21, EtOH)Source of chirality: (1R,2S,5R)-(−)-MentholAbsolute configuration: (8R,10R,11S,14R)
