The Journal of Organic Chemistry
Note
(S)-1-Benzyl-3-((R)-1-hydroxy-2-oxopropyl)-5-methoxy-3-(4-
Na) 427.0264, found 427.0252. The enantiomeric excess of 97% ee
was determined by HPLC (Daicel Chirapak IC-H, hexane/2-propanol
= 70/30, flow rate 0.5 mL/min, T = 30 °C, 254 nm, tR(minor) 11.44
min, tR(major) 25.42 min).
methoxyphenylamino)indolin-2-one (anti-4h): amorphous solid, 66
1
mg; yield 74%; [α]20 = +168.6 (c = 1.18, CHCl3); H NMR (300
D
MHz, CDCl3) δ(ppm) 2.04 (s, 3H), 3.69 (s, 3H), 3.76 (s, 3H), 4.03
(d, J = 9.0 Hz, 1H), 4.50 (d, J = 15.9 Hz,1H), 4.66 (d, J = 9.6 Hz, 1H),
4.85 (s, 1H), 4.96 (d, J = 15.3 Hz, 1H), 6.47−6.57 (m, 5H), 6.72 (d, J
= 8.4 Hz, 1H), 6.87 (d, J = 4.8 Hz, 2H), 7.01 (s, 1H), 7.18−7.19 (m,
2H), 7.26 (s, 1H); 13C NMR (75 MHz, CDCl3) δ (ppm) 29.3, 43.9,
55.3, 55.8, 68.4, 80.1, 110.5, 112.0, 114.2, 114.5, 122.2, 127.1, 127.4,
127.5, 128.5, 135.0, 136.8, 137.5, 155.2, 156.2, 175.5, 206.6; IR (neat)
ν (cm−1) 3422, 2920, 1712, 1605, 1511, 1492, 1385, 1273, 1241, 1179,
1098, 1034, 817, 699; HRMS (ESI) calcd for C26H26N2NaO5 (M+ +
Na) 469.1734, found 469.1727. The enantiomeric excess of 98%ee was
determined by HPLC (Daicel Chirapak IC-H, hexane/2-propanol =
75/25, flow rate 1 mL/min, T = 30 °C, 254 nm, tR(minor) 19.11 min,
tR(major) 52.30 min).
(R)-1-Benzyl-3-((R)-1-hydroxy-2-oxopropyl)-3-(4-
methoxyphenylamino)indolin-2-one (syn-4a): amorphous solid, 73.2
1
mg; yield 88%; [α]20 = −90 (c = 1, CHCl3); H NMR (300 MHz,
D
CDCl3) δ (ppm) 2.10 (s, 3H), 3.67 (s, 3H), 4.16 (s, 2H), 4.55−4.60
(m, 2H), 5.12 (d, J = 15.9 Hz, 1H), 6.52 (s, 4H), 6.58 (d, J = 7.8 Hz,
1H), 6.96−7.06 (m, 3H), 7.15−7.27 (m, 4H), 7.51(d, J = 7.2 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ (ppm) 27.4, 43.9, 55.3, 69.0, 80.3,
109.7, 114.0, 122.9, 123.2, 125.6, 125.7, 127.2, 127.5, 128.6, 129.8,
134.9, 136.7, 143.1, 155.5, 175.9, 207.6; IR (neat) ν (cm−1) 3423,
2920, 1712, 1613, 1511, 1439, 1383, 1357, 1241, 1178, 1081, 1032,
754, 698; HRMS (ESI) calcd for C25H24N2NaO4 (M+ + Na) 439.1628,
found 439.1624. The enantiomeric excess of 90% ee was determined
by HPLC (Daicel Chirapak IC-H, hexane/2-propanol = 75/25, flow
rate 1 mL/min, T = 30 °C, 254 nm, tR(major) 10.12 min, tR(minor)
29.39 min).
(S)-1-Benzyl-6-bromo-3-((R)-1-hydroxy-2-oxopropyl)-3-(4-
methoxyphenylamino)indolin-2-one (anti-4i): amorphous solid, 89.1
1
mg; yield 90%; [α]20 = +82.4 (c = 1.08, CHCl3); H NMR (300
D
MHz, CDCl3) δ (ppm) 2.24 (s, 3H), 3.70 (s, 3H), 3.95 (d, J = 8.7 Hz,
1H), 4.53 (d, J = 15.6 Hz, 1H), 4.67 (d, J = 9.0 Hz, 1H), 4.77 (s, 1H),
4.94 (d, J = 15.6 Hz, 1H), 6.47−6.50 (m, 2H), 6.55−6.58 (m, 2H),
6.72−6.72 (m, 1H), 6.84−6.87 (m, 2H), 7.17−7.22 (m, 5H); 13C
NMR (75 MHz, CDCl3) δ (ppm) 29.6, 43.8, 55.3, 68.6, 79.5, 113.3,
114.2, 122.9,123.8, 124.8, 125.8, 126.2, 126.9, 127.7, 128.7, 134.3,
136.8, 145.0, 155.5, 176.0, 207.0; IR (neat) ν (cm−1) 3424, 2921,
1715, 1606, 1510, 1485, 1454, 1429, 1355, 1242, 1127, 1003, 824, 733;
HRMS (ESI) calcd for C25H23BrN2NaO4 (M+ + Na) 517.0733, found
517.0722. The enantiomeric excess of 85% ee was determined by
HPLC (Daicel Chirapak IC-H, hexane/2-propanol = 70/30, flow rate
0.5 mL/min, T = 30 °C, 254 nm, tR(minor) 13.94 min, tR(major)
26.45 min).
(R)-1-Benzyl-3-((R)-1-hydroxy-2-oxopropyl)-3-(4-methoxypheny-
lamino)-5-methylindolin-2-one (syn-4g): amorphous solid, 72.7 mg;
1
yield 84%; [α]20 = −154 (c = 1, CHCl3); H NMR (300 MHz,
D
CDCl3) δ (ppm) 2.10 (s, 3H), 2.29 (s, 3H), 3.66 (s, 3H), 4.28 (s, 1H),
4.53−4.57 (m, 2H), 5.09 (d, J = 15.6 Hz, 1H), 6.47−6.53 (m, 5H),
6.95−6.98 (m, 3H), 7.20−7.21 (m, 3H), 7.30 (s, 1H); 13C NMR (75
MHz, CDCl3) δ (ppm) 21.1, 27.4, 44.0, 55.3, 68.9, 80.3, 109.5, 114.1,
122.5, 125.8, 126.1, 127.3, 127.5, 128.6, 130.2, 132.5, 135.0, 137.0,
140.6, 155.3, 175.8, 207.4; IR (neat) ν (cm−1) 3411, 2920, 1713, 1620,
1604, 1511, 1494, 1382, 1352, 1242, 1178, 1097, 1034, 812, 666;
HRMS (ESI) calcd for C26H26N2NaO4 (M+ + Na) 453.1785, found
453.1782. The enantiomeric excess of 91% ee was determined by
HPLC (Daicel Chirapak IC-H, hexane/2-propanol = 75/25, flow rate
1 mL/min, T = 30 °C, 254 nm, tR(major) 9.96 min, tR(minor) 29.50
min).
(S)-1-Benzyl-3-((R)-1-hydroxy-2-oxopropyl)-3-(4-methoxypheny-
lamino)-5-(trifluoromethoxy)indolin-2-one (anti-4j): amorphous
solid, 96.6 mg; yield 97%; [α]20 = +99.5 (c = 1.0, CHCl3); 1H
(R)-1-Benzyl-3-((R)-1-hydroxy-2-oxopropyl)-5-methoxy-3-(4-
D
methoxyphenylamino)indolin-2-one (syn-4h): amorphous solid, 75.6
NMR (300 MHz, CDCl3) δ (ppm) 2.21 (s, 3H), 3.69 (s, 3H), 4.55 (d,
J = 15.9 Hz, 1H), 4.72 (s, 1H), 4.97 (d, J = 16.2 Hz, 1H), 6.50−6.58
(m, 5H), 6.83−6.85 (m, 2H), 7.05−7.07 (m, 1H), 7.18−7.23 (m, 4H);
13C NMR (75 MHz, CDCl3) δ (ppm) 29.4, 43.9, 55.3, 69.0, 79.5,
110.4, 114.1, 119.1, 123.2, 123.5, 126.9, 127.5, 127.7, 128.7, 134.3,
136.6, 142.3, 144.6, 144.7, 155.7, 176.0, 206.9; IR (neat) ν (cm−1)
3420, 3263, 1719, 1681, 1620, 1511, 1491, 1453, 1256, 1220, 1179,
1036, 830, 699; HRMS (ESI) calcd for C26H23F3N2NaO5 (M+ + Na)
523.1451, found 523.1448. The enantiomeric excess of 94% ee was
determined by HPLC (Daicel Chirapak IC-H, hexane/2-propanol
=70/30, flow rate 0.5 mL/min, T = 30 °C, 254 nm, tR(minor) 14.70
min, tR(major) 27.00 min).
1
mg; yield 85%; [α]20 = −143 (c = 1, CHCl3); H NMR (300 MHz,
D
CDCl3) δ (ppm) 2.11 (s, 3H), 3.67 (s, 3H), 3.74 (s, 3H), 4.36 (s, 1H)
4.50−4.55 (m, 2H), 5.09 (d, J = 15.6 Hz, 1H), 6.48−6.51 (m, 5H),
6.67 (d, J = 8.4 Hz, 1H), 6.95 (m, 2H), 7.11 (s, 1H), 7.20−7.26 (m,
3H); 13C NMR (75 MHz, CDCl3) δ (ppm) 27.5, 44.0, 55.3, 55.7, 69.2,
80.2, 110.2, 112.5, 114.1, 114.3, 122.7, 127.1, 127.3, 127.6, 128.6,
134.9, 136.3, 136.8, 155.3, 156.0, 175.6, 207.4; IR (neat) ν (cm−1)
3422, 2920, 1712, 1605, 1511, 1492, 1385, 1273, 1241, 1179, 1098,
1034, 817, 699; HRMS (ESI) calcd for C26H26N2NaO5 (M+ + Na)
469.1734, found 469.1727. The enantiomeric excess of 91% ee was
determined by HPLC (Daicel Chirapak IC-H, hexane/2-propanol =
75/25, flow rate 1 mL/min, T = 30 °C, 254 nm, tR(major) 12.91 min,
tR(minor) 32.34 min).
(S)-3-((R)-1-Hydroxy-2-oxopropyl)-3-(4-methoxyphenylamino)-
indolin-2-one (anti-4k): amorphous solid, 63.7 mg; yield 98%; [α]20
D
(R)-1-Benzyl-6-bromo-3-((R)-1-hydroxy-2-oxopropyl)-3-(4-
= +52.1 (c = 0.96, CHCl3); 1H NMR (300 MHz, DMSO-d6) δ (ppm)
2.19 (s, 3H), 3.54 (s, 3H), 4.32 (s, 1H), 5.70 (s, 1H) 5.86 (s, 1H), 6.22
(d, J = 7.8 Hz, 2H), 6.52 (d, J = 7.5 Hz, 2H), 6.81−6.97 (m, 3H),
7.18−7.20 (m, 1H), 10.56 (s, 1H); 13C NMR (75 MHz, DMSO-d6) δ
(ppm) 29.2, 55.5, 68.0, 79.3, 110.3, 114.6, 116.8, 121.8, 125.0, 127.5,
129.6, 139.7, 143.4, 152.5, 177.5, 210.5; IR (neat) ν (cm−1) 3417,
1718, 1620, 1512, 1470, 1354, 1182, 1097, 1035, 946, 758; HRMS
(ESI) calcd for C18H18N2NaO4 (M+ + Na) 349.1159, found 349.1166.
The enantiomeric excess of 99% ee was determined by HPLC (Daicel
Chirapak IC-H, hexane/2-propanol = 70/30, flow rate 0.5 mL/min, T
= 30 °C, 254 nm, tR(minor) 15.62 min, tR(major) 25.11 min).
(S)-6-Bromo-3-((R)-1-hydroxy-2-oxopropyl)-3-(4-
methoxyphenylamino)indolin-2-one (syn-4i): amorphous solid, 81
1
mg; yield 82%; [α]20 = −78 (c = 1, CHCl3); H NMR (300 MHz,
D
CDCl3) δ (ppm) 2.13 (s, 3H), 3.70 (s, 3H), 4.27 (s, 1H), 4.52 (m,
2H), 5.07 (d, J = 16.2 Hz,1H), 6.55 (m, 4H), 6.73 (s, 1H), 6.94 (m,
2H), 7.17−7.24 (m, 4H), 7.37−7.40 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ (ppm) 27.4, 44.0, 55.3, 68.9, 80.1, 113.0, 114.1, 123.6, 123.7,
124.7, 125.8, 126.8, 127.1, 127.8, 128.7, 134.2, 136.1, 144.5, 155.9,
175.8, 207.1; IR (neat) ν (cm−1) 3424, 2921, 1715, 1606, 1510, 1485,
1454, 1429, 1355, 1242, 1127, 1003, 824, 733; HRMS (ESI) calcd for
C25H23BrN2NaO4 (M+ + Na) 517.0733, found 517.0722; The
enantiomeric excess of 86% ee was determined by HPLC (Daicel
Chirapak IC-H, hexane/2-propanol = 70/30, flow rate 0.5 mL/min, T
= 30 °C, 254 nm, tR(major) 12.62 min, tR(minor) 29.03 min).
methoxyphenylamino)indolin-2-one (anti-4l): amorphous solid, 73.4
1
mg; yield 91%; [α]20 = +43 (c = 1, CHCl3); H NMR (300 MHz,
D
DMSO-d6) δ (ppm) 2.18 (s, 3H), 3.51 (s, 3H), 4.29 (d, J = 6.3 Hz,
1H), 5.71 (s, 1H), 5.92 (d, J = 6.0 Hz, 1H), 6.18 (d, J = 8.7 Hz, 2H),
6.51 (d, J = 8.4 Hz, 2H), 6.84−7.04 (m, 3H), 10.67 (s, 1H); 13C NMR
(75 MHz, DMSO-d6) δ (ppm) 29.3, 55.5, 68.0, 79.0, 113.0, 114.6,
117.0, 122.2, 124.4, 126.9, 127.0, 139.4, 145.2, 152.7, 177.5, 210.1; IR
(neat) ν (cm−1) 3419, 2920, 1725, 1612, 1511, 1480, 1446, 1357,
1241, 1076, 908, 822, HRMS (ESI) calcd for C18H17BrN2NaO4 (M+ +
ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR, 13C NMR, and HPLC spectra for products and
crystal data for anti-5i. This material is available free of charge
3593
dx.doi.org/10.1021/jo202585w | J. Org. Chem. 2012, 77, 3589−3594