| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1345044 | Tetrahedron: Asymmetry | 2014 | 7 Pages |
The organocatalyzed enantioselective cascade sulfa-Michael/Michael addition reaction of (E)-3-mercapto-2-butenoic acid esters to (E)-3-aryl-2-(indol-3-ylcarbonyl)acrylonitriles has been developed. This process was promoted by a chiral squaramide catalyst to afford chiral 3-substituted indole derivatives containing tetrahydrothiophene with three contiguous stereocenters in excellent diastereoselectivities (up to >20:1 dr) with moderate to good yields and enantioselectivities (up to 93%, 89% ee).
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(3S,4R,5S)-[4-Cyano-4-(1H-indole-3-carbonyl)-5-phenyl-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC24H22N2O3See = 63%, dr = 16:1[α]D25 = −28.3 (c 1.76, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-Cyano-4-(1H-indole-3-carbonyl)-5-(2-methoxy-phenyl)-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC25H24N2O4See = 89%, dr = >20:1[α]D25 = −43.8 (c 1.81, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-Cyano-4-(1H-indole-3-carbonyl)-5-o-tolyl-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC25H24N2O3See = 72% dr = >20:1[α]D25 = −20.9 (c 1.88, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-Cyano-5-(4-fluoro-phenyl)-4-(1H-indole-3-carbonyl)-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC24H21FN2O3See = 62%, dr = >20:1[α]D25 = −42.2 (c 1.25, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[5-(4-Chloro-phenyl)-4-cyano-4-(1H-indole-3-carbonyl)-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC24H21ClN2O3See = 50%, dr = >20:1[α]D25 = −39.6 (c 1.34, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[5-(4-Bromo-phenyl)-4-cyano-4-(1H-indole-3-carbonyl)-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC24H21BrN2O3See = 43%, dr = >20:1[α]D25 = −37.4 (c 1.08, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-Cyano-4-(1H-indole-3-carbonyl)-5-(4-methoxy-phenyl)-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC25H24N2O4See = 62%, dr = >20:1[α]D25 = −44.9 (c 2.19, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-Cyano-4-(1H-indole-3-carbonyl)-5-p-tolyl-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC25H24N2O3See = 55%, dr = >20:1[α]D25 = −53.3 (c 1.74, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-Cyano-4-(1H-indole-3-carbonyl)-5-naphthalen-1-yl-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC28H24N2O3See = 46%, dr = >20:1[α]D25 = +12.9 (c 1.46, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-Cyano-4-(5-methoxy-1H-indole-3-carbonyl)-5-phenyl-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC25H24N2O4See = 57%, dr = >20:1[α]D25 = −63.8 (c 1.31, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-Cyano-4-(5-methyl-1H-indole-3-carbonyl)-5-phenyl-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC25H24N2O3See = 52%, dr = >20:1[α]D25 = −78.5 (c 1.18, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-Cyano-4-(1-methyl-indole-3-carbonyl)-5-phenyl-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC25H24N2O3See = 52%, dr = >20:1[α]D25 = −93.3 (c 0.59, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[4-(5-Chloro-1H-indole-3-carbonyl)-4-cyano-5-phenyl-tetrahydrothiophen-3-yl]-acetic acid ethyl esterC24H21ClN2O3See = 10%, dr = >20:1[α]D25 = −31.1 (c 1.22, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
(3S,4R,5S)-[5-(4-Bomophenyl)-4-cyano-4-(1H-indole-3-carbonyl)-tetrahydrothiophen-3-yl]-acetic acid tert-butyl esterC26H25BrN2O3See = 50%, dr = >20:1[α]D25 = +54.6 (c 1.59, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (3S,4R,5S)
