The Journal of Organic Chemistry
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disappearance of the substrate, the reaction mixture was cooled to 0
°C again. The reaction mixture was quenched with saturated aqueous
NH4Cl (1 mL) and extracted with CH2Cl2 (3 × 5 mL). The combined
organic layers were dried over anhydrous Na2SO4. After filtration and
evaporation of the solvent, the crude residue was resolved in 0.3 mL of
dioxane again. After addition of 0.2 mL of saturated HCl, the mixture
was stirred at room temperature for 15 min, saturated aqueous
NaHCO3 was added dropwise until gas was no longer evolved upon
addition, and the resulting mixture was extracted with CH2Cl2 (3 × 10
mL). The combined organic layers were dried over Na2SO4. After
filtration and evaporation of the solvent, the crude residue was purified
by flash chromatography (silica gel, hexane/ethyl acetate).
(S)-3-Amino-1-benzyl-3-methylindolin-2-one (3a′). ((SS)-N-tert-
butanesulfinyl ketimine was employed initially.) White amorphous
solid, 42 mg (83% yield). 98% ee determined by HPLC analysis
(Daicel Chiralcel AD column, hexane/2-propanol 90:10, 1.0 mL/min).
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Retention time: tmajor = 16.5 and tminor = 14.2 min. [α]D = −50 (c =
1.0, CHCl3).1H NMR (300 MHz, CDCl3): δ 7.41 (dd, J = 7.3, 0.8 Hz,
1H), 7.35 − 7.26(m, 5H), 7.19 (td, J = 7.7, 1.2 Hz, 1H), 7.10 − 7.02
(m, 1H), 6.74 (d, J = 7.7 Hz, 1H), 4.98 (d, J = 15.9 Hz, 1H), 4.82 (d, J
= 15.6 Hz, 1H), 1.82 (s, 2H), 1.52 (s, 3H).13C NMR (75 MHz,
CDCl3): δ 181.2, 141.7, 135.8, 133.2, 128.9, 127.7, 127.2, 123.4, 123.0,
109.3, 57.9, 43.7, 25.7. IR (KBr): ν = 3358, 2970, 2922, 1713, 1614,
1489, 1467, 1354, 1181, 1001, 753, 699 cm−1. HRMS: calcd for
C16H16N2O + H+ 253.1341, found 253.1345.
(RS)-2-Methyl-N-(3-methyl-2-oxoindolin-3-yl)propane-2-sulfina-
mide (2a). ((RS)-N-tert-Butanesulfinyl ketimine was employed
(R)-3-Amino-1-benzyl-4-chloro-3-methylindolin-2-one (3b).
((RS)-N-tert-butanesulfinyl ketimine was employed initially.) White
amorphous solid, 51 mg (89% yield). 92% ee determined by HPLC
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initially.) White amorphous solid, 30 mg (56% yield). [α]D = −59
1
(c = 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 9.34 (s, 0.45H),
9.13 (s, 0.55H), 7.43 (d, J = 7.2, 0.6H), 7.27−7.20 (m, 1.4H), 7.1−
7.01 (m, 1H), 6.89 (d, J = 15.6 Hz, 1H), 4.98 (d, J = 8.4 Hz, 1H), 4.57
(s, 0.45H), 4.25 (s, 0.55H), 1.66 (s, 1.6H), 1.56 (s, 1.4H), 1.23 (s,
4H), 1.19 (s, 5H). 13C NMR (75 MHz, CDCl3): δ 180.0, 179.0, 141.2,
140.4, 131.0, 129.7, 129.5, 129.3, 124.9, 124.8, 122.8, 122.5, 111.1,
110.6, 61.5, 61.0, 56.4, 56.1, 24.94, 24.86, 22.7, 22.4. IR (KBr): ν =
3181, 2979, 2919, 1721, 1621, 1473, 1367, 1329, 1204, 752, 663 cm−1.
HRMS: calcd for C13H18N2O2S + Na+ 289.0981, found 289.0984.
(RS)-N-((R)-1,3-Dimethyl-2-oxoindolin-3-yl)-2-methylpropane-2-
analysis (Daicel Chiralcel AD column, hexane/2-propanol 90:10, 1.0
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mL/min). Retention time: tmajor = 30.0 and tminor = 33.1 min. [α]D
=
+46 (c = 1.0, CHCl3).1H NMR (300 MHz, CDCl3) δ 7.37 − 7.21 (m,
5H), 7.10 (t, J = 8.0 Hz, 1H), 6.97 (dd, J = 8.2, 0.7 Hz, 1H), 6.63 (dd,
J = 7.8, 0.6 Hz, 1H), 4.98 (d, J = 15.9 Hz, 1H), 4.81 (d, J = 15.6 Hz,
1H), 1.92 (s, 2H), 1.71 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 179.3,
143.4, 135.3, 130.9, 129.8, 129.6, 128.9, 127.8, 127.1, 123.9, 108.0,
59.1, 43.8, 23.8. IR (KBr): ν = 3365, 2963, 2925, 2023, 1722, 1607,
1457, 1371, 1343, 1171, 779, 734, 699 cm−1. HRMS: calcd for
C16H15ClN2O + H+ 287.0946, found 287.0952.
sulfinamide (2b). ((RS)-N-tert-Butanesulfinyl ketimine was employed
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initially.) Pale yellow amorphous solid, 44 mg (78% yield). [α]D
=
(R)-3-Amino-1-benzyl-4-bromo-3-methylindolin-2-one (3c).
((RS)-N-tert-butanesulfinyl ketimine was employed initially.) White
amorphous solid, 53 mg (85% yield). 98% ee determined by HPLC
−55 (c = 1.0, CHCl3).1H NMR (300 MHz, CDCl3): δ 7.52 (d, J = 7.2,
1H), 7.36 (t, J = 7.5, 1H), 7.13 (t, J = 7.5, 1H), 6.88 (d, J = 7.8, 1H),
3.81 (s, 1H), 3.23 (s, 3H), 1.67 (s, 3H), 1.16 (s, 9H). 13C NMR (75
MHz, CDCl3): δ 176.7, 142.7, 130.4, 129.5, 124.9, 123.1, 108.5, 61.1,
56.3, 26.4, 25.4, 22.3. IR (KBr): ν = 3216, 2959, 2924, 1720, 1613,
1472, 1370, 1058, 752, cm−1. HRMS calcd for C14H20N2O2S + Na+:
303.1138, found 303.1149.
analysis (Daicel Chiralcel AD column, hexane/2-propanol 90:10, 1.0
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mL/min). Retention time: tmajor = 23.6 and tminor = 25.5 min. [α]D
=
1
+32 (c = 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 7.36 − 7.21
(m, 5H), 7.15 (dd, J = 8.2, 0.8 Hz, 1H), 7.03 (t, J = 8.0 Hz, 1H), 6.67
(dd, J = 7.7, 0.7 Hz, 1H), 4.99 (d, J = 15.9 Hz, 1H), 4.81 (d, J = 15.6
Hz, 1H), 1.95 (s, 2H), 1.71 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
179.3, 143.6, 135.3, 123.0, 128.9, 127.8, 127.1, 127.0, 118.9, 108.5,
59.8, 43.8, 23.7. IR (KBr): ν = 3363, 2964, 2924, 2023, 1719, 1608,
1489, 1371, 1178, 804, 700 cm−1. HRMS: calcd for C16H15BrN2O +
H+ 331.0446, found 331.0441.
(RS)-N-((R)-1-Benzyl-3-methyl-2-oxoindolin-3-yl)-2-methylpro-
pane-2-sulfinamide (2c). ((RS)-N-tert-Butanesulfinyl ketimine was
employed initially.) Pale yellow solid, mp = 77−78 °C, 57 mg (80%
yield). [α]Drt = −17 (c = 1.0, CHCl3). 1H NMR (300 MHz, CDCl3): δ
7.54 (d, J = 6.6, 1H), 7.33 − 7.20 (m, 6H), 7.10 (m, 1H), 6.74 (d, J =
7.8, 1H), 4.96 (d, J = 15.9, 1H), 4.87 (d, J = 15.9, 1H), 3.88 (s, 1H),
1.73 (s, 3H), 1.17 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 176.9,
141.9, 135.4, 130.2, 129.5, 128.8, 127.7, 127.1, 125.2, 123.1, 109.6,
61.3, 56.4, 43.7, 25.6, 22.4. IR (KBr): ν = 3243, 2959, 2925, 1718,
1611, 1488, 1469, 1365, 1184, 1058, 752, cm−1. HRMS calcd for
C20H24N2O2S + H+ 357.1631, found 357.1636.
Ethyl 2-((R)-3-((RS)-1,1-Dimethylethylsulfinamido)-3-methyl-2-
oxoindolin-1-yl)acetate (2d). ((RS)-N-tert-Butanesulfinyl ketimine
was employed initially.) Yellow amorphous solid, 44 mg (62%
yield). [α]Drt = −28 (c = 1.0, CHCl3).1H NMR (300 MHz, CDCl3): δ
7.55 (d, J = 7.2, 1H), 7.35 − 7.28 (m, 1H), 7.15 (t, J = 7.2, 1H), 6.75
(d, J = 7.8, 1H), 4.52 (d, J = 17.4, 1H), 4.39 (d, J = 17.7, 1H), 4.21 (q,
J = 7.2, 2H), 3.85 (s, 1H), 1.71 (s, 3H), 1.25 (t, J = 7.2, 3H), 1.
Seventeen (s, 9H). 13C NMR (75 MHz, CDCl3): δ 176.8, 167.2,
141.4, 130.0, 129.6, 125.2, 123.5, 123.2, 108.5, 61.9, 61.2, 56.4, 41.4,
25.7, 22.6, 22.3, 14.1. IR (KBr): ν = 3260, 2981, 2953, 1749, 1713,
1610, 1468, 1374, 1207, 1183, 1063, 1015, 760, cm−1. HRMS calcd for
C17H24N2O4S + Na+ 375.1349, found 375.1359.
(S)-3-Amino-1-benzyl-4-bromo-3-methylindolin-2-one (3c′).
((SS)-N-tert-Butanesulfinyl ketimine was employed initially.) White
amorphous solid, 54 mg (86% yield). 98% ee determined by HPLC
analysis (Daicel Chiralcel AD column, hexane/2-propanol 90:10, 1.0
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mL/min). Retention time: tmajor = 25.5 and tminor = 23.6 min. [α]D
=
−34 (c = 1.0, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.37 − 7.21 (m,
5H), 7.15 (dd, J = 8.2, 0.7 Hz, 1H), 7.03 (t, J = 8.0 Hz, 1H), 6.67 (dd,
J = 7.7, 0.6 Hz, 1H), 4.99 (d, J = 15.6 Hz, 1H), 4.81 (d, J = 15.6 Hz,
1H), 1.93 (s, 2H), 1.71 (s, 3H).13C NMR (75 MHz, CDCl3) δ 179.3,
143.6, 135.3, 131.3, 130.0, 128.9, 127.8, 127.1, 127.0, 118.9, 108.5,
59.8, 43.8, 23.7. IR (KBr): ν = 3363, 2957, 2923, 2024, 1722, 1610,
1457, 1370, 1173, 798, 698 cm−1. HRMS: calcd for C16H15BrN2O +
H+ 331.0446, found 331.0444.
(R)-3-Amino-1-benzyl-3,5-dimethylindolin-2-one (3d). ((RS)- N-
tert-Butanesulfinyl ketimine was employed initially.) White amorphous
solid, 40 mg (76% yield). 99% ee determined by HPLC analysis
(Daicel Chiralcel AD column, hexane/2-propanol 90:10, 1.0 mL/min).
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Retention time: tmajor = 12.2 and tminor = 15.9 min. [α]D = +50 (c =
1
(R)-3-Amino-1-benzyl-3-methylindolin-2-one (3a). ((RS)-N-tert-
Butanesulfinyl ketimine was employed initially.) White amorphous
solid, 41 mg (82% yield). 96% ee determined by HPLC analysis
(Daicel Chiralcel AD column, hexane/2-propanol 90:10, 1.0 mL/min).
1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 7.35−7.21 (m, 6H),
6.98 (d, J = 7.9 Hz, 1H), 6.61 (d, J = 7.9 Hz, 1H), 4.96 (d, J = 15.6 Hz,
1H), 4.80 (d, J = 15.6 Hz, 1H), 2.31 (s, 3H), 1.77 (s, 2H), 1.51 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 181.2, 139.3, 135.9, 133.3, 132.6,
129.0, 128.8, 127.6, 127.2, 124.2, 109.1, 57.9, 43.7, 25.7, 21.0. IR
(KBr): ν = 3284, 2964, 2923, 2022, 1713, 1602, 1496, 1373, 1262,
1178, 1099, 1026, 804, 697 cm−1. HRMS: calcd for C17H18N2O + H+
267.1497, found 267.1494.
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Retention time: tmajor = 14.0 and tminor = 16.6 min. [α]D = +48 (c =
1.0, CHCl3). 1H NMR (300 MHz, CDCl3): δ 7.41 (dd, J = 7.3, 0.8 Hz,
1H), 7.35 − 7.25 (m, 5H), 7.19 (td, J = 7.7, 1.3 Hz, 1H), 7.06 (td, J =
7.6, 0.8 Hz, 1H), 6.74 (d, J = 7.7 Hz, 1H), 4.98 (d, J = 15.6 Hz, 1H),
4.82 (d, J = 15.6 Hz, 1H), 1.82 (s, 2H), 1.52 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 181.2, 141.7, 135.8, 133.2, 128.9, 127.7, 127.2, 123.4,
123.0, 109.3, 57.9, 43.7, 25.7. IR (KBr): ν = 3356, 2957, 2925, 1715,
1611, 1489, 1465, 1377, 1179, 741, 706 cm−1. HRMS: calcd for
C16H16N2O + H+ 253.1341, found 253.1336.
(R)-3-Amino-1-benzyl-5-methoxy-3-methylindolin-2-one (3e).
((RS)-N-tert-butanesulfinyl ketimine was employed initially.) White
amorphous solid, 41 mg (72% yield). 97% ee determined by HPLC
analysis (Daicel Chiralcel AD column, hexane/2-propanol 70:30, 1.0
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mL/min). Retention time: tmajor = 7.6 and tminor = 12.2 min. [α]D
=
3314
dx.doi.org/10.1021/jo300110a | J. Org. Chem. 2012, 77, 3311−3317