The Journal of Organic Chemistry
Article
127.5, 128.3, 130.2, 133.9, 135.2, 136.9, 149.4, 149.8, 192.1. HRMS
(ESI): calcd for C17H14ClO4 [M − H] 317.0581, found 317.0579.
[3-(3,4-Dimethoxyphenyl)oxiran-2-yl]-furan-2-yl-methanone
(2S,3R)-3-(3,4-Dimethoxyphenyl)-2-hydroxy-3-(1-methyl-1H-pyr-
rol-2-yl)-1-phenylpropan-1-one (3b). Obtained using the general
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electrolysis procedure as a yellow oil. Yield: 98.7 mg, 27%. H NMR
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(CDCl3, 400 MHz): δ 3.13 (s, 3H), 3.46 (d, J = 8.0 Hz, 1H), 3.69 (s,
3H), 3.82 (s, 3H), 4.39 (s, 1H), 5.82 (dd, J = 7.6, 2.0 Hz, 1H), 6.17 (t,
J = 3.2 Hz, 1H), 6.35 (dd, J = 4.0, 2.4 Hz, 2H), 6.54 (d, J = 2.0 Hz,
1H), 6.65−6.69 (m, 2H), 7.55 (t, J = 7.6 Hz, 2H), 7.68 (t, J = 7.6 Hz,
1H), 7.96 (d, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 34.1,
47.2, 55.7, 75.2, 106.6, 108.2, 110.6, 112.5, 121.5, 122.0, 128.7, 129.2,
132.5, 134.1, 148.1, 148.5, 200.0. HRMS (ESI): calcd for C22H24NO4
[M + H] 366.1705, found 366.1700.
(2S,3S)-3-(3,4-Dimethoxyphenyl)-2-hydroxy-3-(1-methyl-1H-pyr-
rol-2-yl)-1-phenylpropan-1-one (4b). General electrolysis procedure.
Yellow oil. Yield: 179.1 mg, 49%. 1H NMR (CDCl3, 400 MHz): δ 3.08
(s, 3H), 3.75 (d, J = 6.4 Hz, 1H), 3.78 (s, 3H), 3.80 (s, 3H), 4.44 (d, J
= 5.2 Hz, 1H), 5.56 (t, J = 6.0 Hz, 1H), 6.08−6.09 (m, 1H), 6.24−6.25
(m, 1H), 6.45 (s, 1H), 6.70−6.80 (m, 3H), 7.42 (t, J = 7.6 Hz, 2H),
7.55 (t, J = 7.6 Hz, 1H), 7.74 (d, J = 7.2 Hz, 2H). 13C NMR (100
MHz, CDCl3): δ 33.8, 47.6, 55.8, 55.9, 76.0, 106.8, 108.3, 111.2, 112.0,
120.7, 122.1, 128.3, 128.6, 129.3, 132.0, 133.5, 135.0, 148.0, 148.9,
201.2. HRMS (ESI): calcd for C22H24NO4 [M + H] 366.1705, found
366.1694.
(1e). White crystal. Yield: 4.94 g, 90%. Mp: 125−126 °C. H NMR
(CDCl3, 400 MHz): δ 3.90 (s, 6H), 4.11 (d, J = 1.6 Hz, 1H), 4.13 (d, J
= 2.0 Hz, 1H), 6.61 (dd, J = 3.6, 1.6 Hz, 1H), 6.81 (d, J = 2.0 Hz, 1H),
6.87 (d, J = 8.4 Hz, 1H), 6.95 (dd, J = 8.4, 2.0 Hz, 1H), 7.47 (d, J = 3.6
Hz, 1H), 7.68 (d, J = 0.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ
55.9, 56.0, 59.8, 60.7, 108.0, 111.1, 112.7, 118.9, 119.6, 127.7, 147.7,
149.3, 149.7, 151.2, 182.1. HRMS (ESI): calcd for C15H13O5 [M − H]
273.0763, found 273.0766.
[3-(3,4,5-Trimethoxyphenyl)oxiran-2-yl]phenylmethanone (1f).13
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White solid. Yield: 5.85 g, 93%. Mp: 111−112 °C. H NMR (CDCl3,
400 MHz): δ3.87 (s, 3H), 3.89 (s, 6H), 4.04 (d, J = 1.6 Hz, 1H), 4.27
(d, J = 2.0 Hz, 1H), 6.60 (s, 2H), 7.51 (t, J = 7.6 Hz, 2H), 7.62−7.66
(m, 1H), 8.03 (d, J = 7.2 Hz, 2H).
Phenyl(3-phenyloxiran-2-yl)methanone (1g).14 White solid. Yield:
4.04 g, 90%. Mp: 83−84 °C. 1H NMR (CDCl3, 400 MHz): δ 4.09 (s,
1H), 4.31 (d, J = 2.0 Hz, 1H), 7.37−7.43 (m, 5H), 7.50 (t, J = 7.6 Hz,
2H), 7.63 (t, J = 7.6 Hz, 1 H), 8.02 (d, J = 8.0 Hz, 2H).
[3-(4-Methoxyphenyl)oxiran-2-yl]phenylmethanone (1h).15
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White solid. Yield: 4.63 g, 91%. Mp: 77−78 °C. H NMR (CDCl3,
(2S,3R)-3-(3,4-Dimethoxyphenyl)-2-hydroxy-1-phenyl-3-(1H-pyr-
rol-2-yl)propan-1-one (3c). Brown solid. Yield: 56.2 mg, 16%. Mp:
52−53 °C. 1H NMR (CDCl3, 400 MHz): δ 3.65 (s, 3H), 3.80 (s, 3H),
3.98 (d, J = 7.2 Hz, 1H), 4.58 (s, 1H), 5.73 (dd, J = 7.2, 2.0 Hz, 1H),
6.12 (s, 1H), 6.20 (dd, J = 5.6, 3.2 Hz, 1H), 6.32 (d, J = 1.6 Hz, 1H),
6.40 (dd, J = 8.4, 2.0 Hz, 1H), 6.65 (d, J = 8.4 Hz, 1H), 6.79−6.80 (m,
1H), 7.56 (t, J = 7.6 Hz, 2H), 7.69 (t, J = 7.6 Hz, 1H), 7.93 (d, J = 6.8
Hz, 2H), 9.17 (bs, 1H). 13C NMR (100 MHz, CDCl3): δ 47.9, 55.6,
55.7, 76.2, 106.4, 108.1, 110.7, 112.0, 117.3, 121.0, 128.2, 129.2 130.0,
132.0, 134.0, 134.3, 148.1, 148.3, 199.6. HRMS (ESI): calcd for
C21H22NO4 [M + H] 352.1549, found 352.1552; calcd for C21H20NO4
[M − H] 350.1392, found 350.1406.
400 MHz): δ 3.83 (s, 3H), 4.03 (d, J = 2.0 Hz, 1H), 4.30 (d, J = 2.0
Hz, 1H), 6.94 (d, J = 8.8 Hz, 2H), 7.31 (d, J = 8.8 Hz, 2H), 7.50 (t, J =
7.6 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 8.02 (d, J = 7.2 Hz, 2H).
[3-(4-Methoxyphenyl)oxiran-2-yl]-(4-methoxyphenyl)methanone
(1i).16 White solid. Yield: 5.17 g, 91%. Mp: 116−117 °C. H NMR
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(CDCl3, 400 MHz): δ 3.83 (s, 3H), 3.98 (s, 3H), 4.02 (d, J = 2.0 Hz,
1H), 4.26 (d, J = 2.0 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.4
Hz, 2H), 7.30 (d, J = 8.8 Hz, 2H), 8.02 (d, J = 8.4 Hz, 2 H).
4.4. General Procedure for the Electrolysis of the Chalcone
Epoxides. To an H-cell was added a solution of LiClO4 supporting
electrolyte (0.2 M) in CH3CN and CH2Cl2 (50 mL, volume ratio =
4:1). Mediator, BMDPI, (0.1 mmol), chalcone epoxide 1 (1 mmol),
and arylation reagent 2 (3 mmol) were added to the cell, respectively.
At room temperature, the solution was electrolyzed at a controlled
potential of 0.88 V vs Ag/AgNO3 (0.1 M in CH3CN) (the first
oxidation peak of BMDPI). The working electrode was platinum net
(25 mm × 35 mm) and the counter electrode was iron rod (d = 7
mm). The electrolysis was monitored by TLC and was terminated
when the starting chalcone epoxide was consumed. After the
electrolysis, the solvent of anode cell was removed by evaporation
under reduced pressure. The residue was dissolved in 20 mL of
dichloromethane and washed with 20 mL of water. The aqueous phase
was extracted with dichloromethane (3 × 10 mL), the combined
organic phases were dried by MgSO4, and column chromatography on
silica gel eluted with a mixture of petroleum ether and EtOAc gave the
pure product.
(2S,3S)-3-(3,4-Dimethoxyphenyl)-2-hydroxy-1-phenyl-3-(1H-pyr-
rol-2-yl)propan-1-one (4c). General electrolysis procedure. Purple
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solid. Yield: 80.8 mg, 23%. Mp: 92−94 °C. H NMR (CDCl3, 400
MHz): δ 3.83 (s, 3H), 3.86 (s, 3H), 3.95 (d, J = 5.6 Hz, 1H), 4.51 (d, J
= 2.8 Hz, 1H), 5.65−5.68 (m, 2H), 6.05 (dd, J = 5.6, 2.8 Hz, 1H),
6.67−6.68 (m, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.92−6.93 (m, 1H), 7.03
(dd, J = 8.4, 2.0 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.62 (t, J = 7.6 Hz,
1H), 7.84 (d, J = 7.2 Hz, 2H), 8.39 (bs, 1H). 13C NMR (100 MHz,
CDCl3): δ 48.0, 55.9, 76.3, 107.5, 107.6, 111.2, 111.8, 117.9, 120.4,
128.5, 128.5, 128.9, 133.0, 133.9, 134.2, 148.0, 149.0, 200.8. HRMS
(ESI) calcd for C21H22NO4 [M + H] 352.1549, foun: 352.1542; calcd
for C21H20NO4 [M − H] 350.1392, found 350.1407.
(2S,3R)-3-(3,4-Dimethoxyphenyl)-2-hydroxy-3-(1-methyl-1H-
indol-3-yl)-1-phenylpropan-1-one (3d). Yellow solid. Yield: 216.1
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mg, 52%. Mp: 71−72 °C. H NMR (CDCl3, 400 MHz): δ 3.66 (s,
(2S,3S)-3-(3,4-Dimethoxyphenyl)-3-(furan-2-yl)-2-hydroxy-1-phe-
3H), 3.76−3.82 (m, 7H), 4.74 (s, 1H), 5.83 (d, J = 5.2 Hz, 1H), 6.52
(s, 1H), 6.56 (d, J = 8.4 Hz, 1H), 6.64 (d, J = 8.4 Hz, 1H), 6.94 (t, J =
7.2 Hz, 1H), 7.17 (t, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 1H), 7.50−
7.53 (m, 3H), 7.65 (t, J = 7.6 Hz, 1H) 7.92 (d, J = 7.6 Hz, 2H). 13C
NMR (100 MHz, CDCl3): δ 32.8, 46.8, 55.7, 76.3, 109.2, 110.6, 112.6,
115.4, 118.9, 119.2, 121.4, 121.7, 127.4, 127.7, 128.6, 129.1, 130.5,
134.0, 134.4, 136.9, 148.0, 148.3, 200.5. HRMS (ESI) calcd for
C26H26NO4 [M + H] 416.1862, found 416.1852.
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nylpropan-1-one (3a). Yellow oil. Yield: 105.7 mg, 30%. H NMR
(CDCl3, 400 MHz): δ 3.70 (s, 3H), 3.76 (d, J = 6.8 Hz, 1H), 3.83 (s,
3H), 4.49 (d, J = 2.8 Hz, 1H), 5.84 (dd, J = 6.8, 2.8 Hz, 1H), 6.33−
6.36 (m, 2H), 6.49−6.52 (m, 2H), 7.70 (d, J = 8.8 Hz, 1H), 7.38 (s,
1H), 7.54 (t, J = 7.6 Hz, 2H), 7.66 (t, J = 7.6 Hz, 1H), 7.90 (d, J = 7.2
Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 49.2, 55.6, 55.7, 74.6, 107.8,
110.4, 110.7, 112.5, 121.5, 127.6, 128.6, 129.0, 134.0, 134.2, 141.6,
148.4, 148.5, 154.6, 199.9. HRMS (ESI) calcd for C21H20NaO5 [M +
Na] 375.1208, found 375.1208.
(2S,3S)-3-(3,4-Dimethoxyphenyl)-2-hydroxy-3-(1-methyl-1H-
indol-3-yl)-1-phenylpropan-1-one (4d). Yellow solid. Yield: 128.8
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(2S,3R)-3-(3,4-Dimethoxyphenyl)-3-(furan-2-yl)-2-hydroxy-1-phe-
mg, 31%. Mp: 69−70 °C. H NMR (CDCl3, 400 MHz): δ 3.72 (s,
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nylpropan-1-one (4a). Yellow oil. Yield: 148.0 mg, 42%. H NMR
3H), 3.77−3.88 (m, 7H), 4.82 (d, J = 2.4 Hz, 1H), 5.76 (dd, J = 7.2,
2.8 Hz, 1H), 6.80−6.86 (m, 2H), 6.92 (d, J = 8.0 Hz, 1H), 6.95 (s,
1H), 7.06−7.12 (m, 3H), 7.21 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 8.0 Hz,
2H), 7.63 (t, J = 7.2 Hz, 1H), 7.83 (d, J = 7.6 Hz, 2H). 13C NMR (100
MHz, CDCl3): δ 32.8, 46.2, 55.9, 56.0, 76.4, 77.3, 109.1, 111.1, 111.3,
112.0, 118.7, 119.0, 120.3, 121.4, 127.7, 128.4, 128.7, 128.8, 133.8,
134.4, 135.5, 136.5, 147.8, 148.9, 200.9. HRMS (ESI): calcd for
C26H24NO4 [M − H] 414.1705, found 414.1708.
(CDCl3, 400 MHz): δ3.86 (s, 3H), 3.87 (s, 3H), 3.87 (d, J = 6.8 Hz,
1H), 4.50 (d, J = 3.2 Hz, 1H), 5.53 (dd, J = 7.2, 3.2 Hz, 1H), 5.98 (d, J
= 3.2 Hz, 1H), 6.25 (dd, J = 3.2, 1.6 Hz, 1H), 6.82 (d, J = 8.4 Hz, 1H),
6.98−7.03 (m, 2H), 7.29 (dd, J = 2.0, 0.8 Hz, 1H), 7.49 (t, J = 7.6 Hz,
2H), 7.62 (t, J = 7.6 Hz, 1H), 7.90 (d, J = 8.4 Hz, 2H). 13C NMR (100
MHz, CDCl3): δ 49.5, 55.9, 75.9, 108.6, 110.2, 111.1, 112.2, 120.9,
128.5, 128.9, 131.5, 133.8, 134.4, 141.8, 148.4, 148.9, 152.7, 200.6.
HRMS (ESI): calcd for C21H20NaO5 [M + Na] 375.1208, found
375.1197.
(2S,3R)-3-(3,4-Dimethoxyphenyl)-2-hydroxy-3-(1H-indol-3-yl)-1-
phenylpropan-1-one (3e). Yellow solid. Yield: 164.6 mg, 41%. Mp:
787
dx.doi.org/10.1021/jo5022184 | J. Org. Chem. 2015, 80, 781−789