Chiral Brønsted acid catalyzed intermolecular Friedel–Crafts alkylation of styrenes with indoles: construction of all-carbon quaternary stereocenters

A chiral Brønsted acid catalyzed Friedel–Crafts reaction of terminal 1,1-diaryalkenes with indoles is described. This reaction provides indole derivatives with acyclic all-carbon quaternary stereocenters in excellent yields and with excellent enantioselectivities, and features high atom efficiency without the generation of side products.

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(S)-2-(1-(1H-Indol-3-yl)-1-(4-methoxyphenyl)ethyl)phenolC23H21NO2[α]D25 = +23.1 (c 0.74, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(5-Methoxy-1H-indol-3-yl)-1-(4-methoxyphenyl)ethyl)phenolC24H23NO3[α]D25 = +45.3 (c 0.70, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(4-Methoxyphenyl)-1-(5-methyl-1H-indol-3-yl)ethyl)phenolC24H23NO2[α]D25 = +27.2 (c 0.71, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(5-Chloro-1H-indol-3-yl)-1-(4-methoxyphenyl)ethyl)phenolC23H20ClNO2[α]D25 = +28.8 (c 0.60, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(5-Bromo-1H-indol-3-yl)-1-(4-methoxyphenyl)ethyl)phenolC23H20BrNO2[α]D25 = +37.9 (c 0.83, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(4-Methoxyphenyl)-1-(5-nitro-1H-indol-3-yl)ethyl)phenolC23H20N2O4[α]D25 = +50.5 (c 0.66, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(6-Fluoro-1H-indol-3-yl)-1-(4-methoxyphenyl)ethyl)phenolC23H20FNO2[α]D25 = +15.2 (c 0.60, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(6-Chloro-1H-indol-3-yl)-1-(4-methoxyphenyl)ethyl)phenolC23H20ClNO2[α]D25 = +19.6 (c 0.56, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(4-Methoxyphenyl)-1-(6-methyl-1H-indol-3-yl)ethyl)phenolC24H23NO2[α]D25 = +15.1 (c 0.53, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(4-Methoxyphenyl)-1-(7-methyl-1H-indol-3-yl)ethyl)phenolC24H23NO2[α]D25 = +28.3 (c 0.54, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(4-((tert-Butyldimethylsilyl)oxy)phenyl)-1-(1H-indol-3-yl)ethyl)phenolC28H33NO2Si[α]D25 = +12.2 (c 0.37, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(4-(Benzyloxy)phenyl)-1-(1H-indol-3-yl)ethyl)phenolC29H25NO2[α]D25 = +14.9 (c 0.71, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(Benzo[d][1,3]dioxol-5-yl)-1-(1H-indol-3-yl)ethyl)phenolC23H19NO3[α]D25 = +35.8 (c 0.52, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(1H-Indol-3-yl)-1-(4-methoxyphenyl)ethyl)-4-methoxyphenolC24H23NO3[α]D25 = +20.3 (c 0.37, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(1H-Indol-3-yl)-1-phenylethyl)-4-methoxyphenolC23H21NO2[α]D25 = +23.1 (c 0.59, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(1H-Indol-3-yl)-1-(4-methoxyphenyl)ethyl)-4-fluorophenolC23H20FNO2[α]D25 = +22.1 (c 0.33, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(1H-Indol-3-yl)-1-(4-methoxyphenyl)ethyl)-5-fluorophenolC23H20FNO2[α]D25 = +16.9 (c 0.49, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(1H-Indol-3-yl)-1-(4-methoxyphenyl)ethyl)-5-methylphenolC24H23NO2[α]D25 = +28.3 (c 0.42, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(4-(Dimethylamino)phenyl)-1-(1H-indol-3-yl)ethyl)phenolC24H24N2O[α]D25 = +22.1 (c 0.14, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(1H-Indol-3-yl)-1-(6-methoxynaphthalen-2-yl)ethyl)phenolC27H23NO2[α]D25 = +13.1 (c 0.51, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)

(S)-2-(1-(1H-Indol-3-yl)-1-(4-methoxyphenyl)ethyl)naphthalen-1-olC27H23NO2[α]D25 = −6.4 (c 0.50, CHCl3)Source of chirality: Enantioselective synthesisAbsolute configuration: (S)