Enantioselective Friedel–Crafts alkylation of indoles with β,γ-unsaturated α-ketoesters catalyzed by new squaramide-linked bisoxazoline–Zn(OTf)2 complexes

Enantioselective Friedel–Crafts alkylation reactions of indoles with β,γ-unsaturated α-ketoesters catalyzed by novel chiral C2-symmetric squaramide-linked bisoxazoline–Zn(OTf)2 complexes were investigated. The corresponding indole ketoesters were obtained in good to excellent yields (up to 98%) and with high enantioselectivities (up to 94% ee). This is the first report on the use of chiral squaramide-linked bisoxazoline SQBOX in a catalytic enanitioselective Friedel–Crafts alkylation reaction.

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(S)-4-(1H-Indol-3-yl)-2-oxo-4-phenylbutyric acid methyl esterC19H17NO3ee = 93%[α]D20 = +26.3 (c 3.15, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-(4-chlorophenyl)butyric acid methyl esterC19H16ClNO3ee = 88%[α]D20 = +20.9 (c 3.35, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-(4-bromophenyl)butyric acid methyl esterC19H16BrNO3ee = 81%[α]D20 = +11.9 (c 3.15, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-(4-florophenyl)butyric acid methyl esterC19H16FNO3ee = 89%[α]D20 = +41.7 (c 3.00, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-(4-methoxyphenyl)butyric acid methyl esterC20H19NO4ee = 89%[α]D20 = +20.1 (c 2.85, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-(4-methylphenyl)butyric acid methyl esterC20H19NO3ee = 91%[α]D20 = +28.0 (c 1.20, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-(4-nitrophenyl)butyric acid methyl esterC19H16N2O5ee = 79%[α]D20 = +13.6 (c 1.70, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-(2-nitrophenyl)butyric acid methyl esterC19H16N2O5ee = 71%[α]D20 = +64.8 (c 1.70, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-(3,4-dimethoxyphenyl)butyric acid methyl esterC21H21NO5ee = 89%[α]D20 = +80.7 (c 3.35, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1-Methyl-1H-indol-3-yl)-2-oxo-4-phenylbutyric acid methyl esterC20H19NO3ee = 32%[α]D20 = +18.7 (c 3.20, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(5-Methyl-1H-indol-3-yl)-2-oxo-4-phenylbutyric acid methyl esterC15H14O3ee = 91%[α]D20 = +11.0 (c 3.00, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(5-Chloro-1H-indol-3-yl)-2-oxo-4-phenylbutyric acid methyl esterC19H16ClNO3ee = 83%[α]D20 = +75.0 (c 3.05, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(5-Methoxy-1H-indol-3-yl)-2-oxo-4-phenylbutyric acid methyl esterC20H19NO4ee = 94%[α]D20 = +96.1 (c 4.35, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-phenylbutyric acid ethyl esterC20H19NO3ee = 89%[α]D20 = +35.4 (c 2.79, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-phenylbutyric acid benzyl esterC25H21NO3ee = 85%[α]D20 = +35.1 (c 3.45, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-phenylbutyric acid isopropyl esterC21H21NO3ee = 86%[α]D20 = +136.0 (c 3.40, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-4-(1H-Indol-3-yl)-2-oxo-4-phenylbutyric acid allyl esterC21H19NO3ee = 89%[α]D20 = +34.4 (c 3.45, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-Methyl 4-(2-hydroxy-4-methoxyphenyl)-2-oxo-4-phenylbutanoateC18H18O5ee = 95%[α]D20 = −2.5 (c 0.40, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)