Molecules 2012, 17
7527
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(230–400 mesh). H-NMR and 13C-NMR spectra were recorded on a Bruker AC 200 instrument
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(200 MHz for H, 50 MHz for C). Chemical shift values () are reported in ppm relative to Me4Si
( 0.0 ppm). Optical rotations were measured on a JASCO-DIP-1000 digital polarimeter with a sodium
lamp. The enantiomeric excesses (ee’s) were determined by HPLC. HPLC analysis was performed on
Younglin M930 Series and Younglin M720 Series, measured at 254 nm using the indicated chiral
column. Mass spectra were obtained on Jeol JMS-DX303 instrument.
3.2. Typical Procedure for the Conjugate Addition Reaction of 3-Phenyloxindole (1a) with Methyl
Vinyl Ketone (2a)
To a solution of 3-phenyloxindole (1a, 0.3 mmol, 93 mg) and catalyst III (0.015 mmol, 11.4 mg) in
toluene (1.8 mL) was added methyl vinyl ketone (2a, 0.36 mmol, 25 mg). Reaction mixture was
stirred for 2 h at room temperature, concentrated, and purified by flash column chromatography
(EtOAc-hexane = 1:3) to afford the Michael adduct 3a (100 mg, 88%).
(R)-tert-Butyl 2-oxo-3-(3-oxobutyl)-3-phenylindoline-1-carboxylate (3a): []21D= + 43.4 (c = 1,
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CHCl3); H-NMR (CDCl3) δ 7.94 (d, J = 8.0 Hz, 1H), 7.42–7.11 (m, 8H), 2.80–2.70 (m, 1H),
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2.55–2.28 (m, 2H), 2.12–2.04 (m, 1H), 2.00 (s, 3H), 1.63 (s, 9H); C-NMR (CDCl3) 206.5, 176.3,
148.8, 139.7, 139.2, 130.2, 128.5, 127.3, 126.5, 124.5, 124.4, 115.1, 84.5, 55.8, 38.5, 31.4, 29.8, 28.0;
HRMS (EI+): m/z calcd for C24H27NO4 [M]+: 393.1940; found 393.1938; HPLC (85:15, n-hexane-i-
PrOH, 254 nm, 1.0 mL/min) Chiralpak AD-H column, tR = 6.85 min (minor), tR = 9.86 min (major),
91% ee.
3.3. Typical Procedure for the Conjugate Addition Reaction of 3-Phenyloxindole (1a) with
1,1-Bis(benzenesulfonyl)ethylene (4a)
To a solution of 3-phenyloxindole (1, 0.3 mmol, 93 mg) and catalyst III (0.015 mmol, 11.4 mg) in
CH2Cl2 (1.2 mL) was added 1,1-bis(benzenesulfonyl)ethylene (4a, 0.45 mmol, 138.7 mg). Reaction
mixture was stirred for 2 h at room temperature, concentrated, and purified by flash column
chromatography (EtOAc-hexane:1:5) to afford the Michael adduct 5a (168 mg, 90%).
(R)-tert-Butyl 3-(2,2-bis(phenylsulfonyl)ethyl)-2-oxo-3-phenylindoline-1-carboxylate (5a): []24D = 24.8
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(c = 0.4, CHCl3); H-NMR (CDCl3) 8.07–7.97 (m, 3H), 7.77–7.67 (m, 3H), 7.64–7.46 (m, 6H),
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7.38–7.16 (m, 7H), 4.45–4.41 (m, 1H), 3.40–3.29 (m, 2H), 1.59 (s, 9H); C-NMR (CDCl3) 175.2,
149.2, 141.2, 140.8, 138.0, 134.7, 134.4, 131.0, 129.3, 128.9, 128.8, 128.0, 126.7, 125.7, 124.6, 116.3,
84.3, 80.6, 55.2, 32.1, 28.0; HPLC (90:10, n-hexane-i-PrOH, 254 nm, 0.5 mL/min) Chiralcel OD-H
column, tR = 18.8 min (major), tR = 23.9 (minor), 91% ee.
4. Conclusions
In conclusion, we have developed a highly efficient catalytic enantioselective conjugate addition
reactions of 3-aryl-substituted oxindoles to methyl vinyl ketone using 5 mol% of binaphthyl-modified
bifunctional catalyst V. The desired Michael products were obtained in good to high yields and
enantioselectivities (81–91% ee) for the 3-aryloxindoles examined in this work. We believe that this