Highly enantioselective Friedel–Crafts alkylation of indole with electron deficient trans-β-nitroalkenes using Zn(II)–oxazoline–imidazoline catalysts

The catalytic asymmetric Friedel–Crafts alkylation of indole with trans-β-nitroolefins has been developed via the catalysis of Zn(II)–oxazoline–imidazoline complexes. The reaction furnished nitroalkylated indoles in excellent yields (up to 95%) and with high enantioselectivities (up to 99% ee). The effects of solvent, temperature, the metal-triflate, and the ligand structure on the reaction are discussed. The substrates of the reaction can be substituted aromatic nitroolifins. The higher reactivity and enantioselectivity of the reaction could be due to the activation and asymmetric induction of chiral Lewis acids coordinated by the nitroolefin through a 1,3-metal bonded intermediate.

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(S)-3-(2-Nitro-1-phenylethyl)-1H-indoleC16H14N2O2ee = 98.7%[α]D20=+29.6 (c 0.9, CH2Cl2)Source of chirality: Asymmetric catalysisAbsolute configuration: (S)

(S)-3-(2-Nitro-1-(p-tolyl)ethyl)-1H-indoleC17H16N2O2ee = 96.6%[α]D20=+19.1 (c 0.9, CH2Cl2)Source of chirality: Asymmetric catalysisAbsolute configuration: (S)

(S)-3-(1-(4-Methoxyphenyl)-2-nitroethyl)-1H-indoleC17H16N2O3ee = 97.2%[α]D20=+31.3 (c 0.9, CH2Cl2)Source of chirality: Asymmetric catalysisAbsolute configuration: (S)

(S)-3-(1-(4-Chlorophenyl)-2-nitroethyl)-1H-indoleC16H13ClN2O2ee = 98.5%[α]D20=+11.7 (c 0.9, CH2Cl2)Source of chirality: Asymmetric catalysisAbsolute configuration: (S)

(S)-3-(1-(4-Bromoophenyl)-2-nitroethyl)-1H-indoleC16H13BrN2O2ee = 96.1%[α]D20=+3.3 (c 0.9, CH2Cl2)Source of chirality: Asymmetric catalysisAbsolute configuration: (S)

(S)-3-(2-Nitro-1-(4-nitrophenyl)ethyl)-1H-indoleC16H13N3O4ee = 94.9%[α]D20=-9.6 (c 0.9, CH2Cl2)Source of chirality: Asymmetric catalysisAbsolute configuration: (S)

(R)-3-(1-(2,4-Dichlorophenyl)-2-nitroethyl)-1H-indoleC16H12Cl2N3O2ee = 98.9%[α]D20=+67.5 (c 0.9, CH2Cl2)Source of chirality: Asymmetric catalysisAbsolute configuration: (R)

(R)-3-(1-(2,6-Dichlorophenyl)-2-nitroethyl)-1H-indoleC16H12Cl2N3O2ee = 97.6%[α]D20=+47.9 (c 0.9, CH2Cl2)Source of chirality: Asymmetric catalysisAbsolute configuration: (R)

(R)-3-(1-Ferrocenyl)-2-nitroethyl)-1H-indoleC20H18FeN2O2ee = 96.9%[α]D20=+27.3 (c 0.9, CH2Cl2)Source of chirality: Asymmetric catalysisAbsolute configuration: (R)