6106
K. C. Nicolaou et al. / Tetrahedron 63 (2007) 6088–6114
126.3, 125.8, 120.4, 120.2, 116.1, 110.3, 52.5, 51.6,
38.5, 29.6, 24.7, 21.0; HRMS (ESI-TOF) calcd for
C16H16BrNO4Na+ [M+Na+] 388.0155, found 388.0148.
gel, EtOAc/hexanes, 4:6); IR (film) nmax 3309, 2972, 2868,
1712, 1689, 1515, 1464, 1440, 1379, 1346, 1271, 1234,
1182, 1140, 1117, 1042, 1000, 878, 798, 775, 742 cmꢁ1
;
1H NMR (600 MHz, CD3CN) d 9.49 (br s, 1H), 7.49 (br s,
1H), 7.33 (br s, 1H), 7.18 (t, J¼7.2 Hz, 1H), 3.90 (s, 3H),
3.67 (br s, 2H), 3.30 (hept, J¼6.6 Hz, 1H), 1.04 (d,
J¼6.6 Hz, 6H), 0.97 (s, 6H); 13C NMR (150 MHz,
CD3CN) d 220.1, 162.9, 137.6, 128.1, 127.2, 126.6, 121.8,
116.1, 115.6, 110.4, 52.6, 50.6, 35.0, 29.5, 23.0 (2C), 20.4
(2C); HRMS (ESI-TOF) calcd for C18H22BrNO4Na+
[M+Na+] 418.0624, found 418.0620.
4.5.24. Methyl 4-bromo-1-hydroxy-3-[(1-oxo-1,2,3,4-tet-
rahydronaphthalen-2-yl)methyl]-1H-indole-2-carboxyl-
ate (39). Rf¼0.35 (silica gel, EtOAc/hexanes, 4:6); IR (film)
nmax 3310, 2944, 2850, 1708, 1676, 1598, 1519, 1451, 1399,
1352, 1300, 1242, 1221, 1116, 1022, 980, 881, 776,
734 cmꢁ1; 1H NMR (400 MHz, CD3CN) d 9.27 (br s, 1H),
7.92 (d, J¼7.7 Hz, 1H), 7.51–7.43 (m, 2H), 7.31 (t,
J¼7.7 Hz, 2H), 7.26 (d, J¼7.7 Hz, 1H), 7.18 (t, J¼7.7 Hz,
1H), 4.06 (br s, 1H), 3.74 (s, 3H), 3.39 (br s, 1H), 3.02–
2.92 (m, 2H), 2.91–2.80 (m, 1H), 2.07–1.97 (m, 1H), 1.95
(s, 1H); 13C NMR (125 MHz, CD3CN) d 199.7, 162.8,
145.4, 138.0, 134.1, 133.4, 129.9, 127.7, 127.4, 127.2,
126.5, 126.2, 120.8, 119.8, 116.2, 110.4, 52.5, 50.6, 29.0,
28.7, 24.9; HRMS (ESI-TOF) calcd for C21H18BrNO4Na+
[M+Na+] 450.0311, found 450.0297.
4.5.29. Methyl 4-bromo-3-(2,2-difluoro-3-oxo-3-phenyl-
propyl)-1-hydroxy-1H-indole-2-carboxylate (44).
Rf¼0.47 (silica gel, EtOAc/hexanes, 4:6); IR (film) nmax
3360, 2955, 2919, 1698, 1520, 1449, 1311, 1264, 1184,
1
1127, 914, 764, 716 cmꢁ1; H NMR (500 MHz, CD3CN)
d 9.24 (br s, 1H), 8.04–8.02 (m, 2H), 7.68 (t, J¼7.3 Hz,
1H), 7.53–7.50 (m, 3H), 7.38–7.36 (m, 1H), 7.24–7.21 (m,
1H), 4.46 (t, J¼17.7 Hz, 2H), 3.80 (s, 3H); 13C NMR
(125 MHz, CD3CN) d 190.5, 162.1, 137.2, 135.4, 133.0,
130.7 (t, J¼3.4 Hz, 2C), 129.7 (2C), 127.4, 127.2, 127.1,
121.1, 119.1, 115.9, 110.4, 108.9, 52.7, 29.7 (t, J¼23.8 Hz);
HRMS (ESI-TOF) calcd for C19H15BrF2NO+4 [M+H+]
438.0147, found 438.0145.
4.5.25. Methyl 4-bromo-1-hydroxy-3-(2-methyl-3-oxo-
pentyl)-1H-indole-2-carboxylate (40). Rf¼0.37 (silica
gel, EtOAc/hexanes, 4:6); IR (film) nmax 3300, 2965, 2923,
1708, 1680, 1514, 1441, 1341, 1247, 1184, 1148, 1116,
1090, 1033, 975, 881, 771, 734 cmꢁ1; 1H NMR (600 MHz,
CD3CN) d 9.22 (br s, 1H), 7.45 (d, J¼7.9 Hz, 1H), 7.32
(d, J¼7.9 Hz, 1H), 7.19 (t, J¼7.9 Hz, 1H), 3.91 (s, 3H),
3.49 (br s, 1H), 3.35 (br s, 1H), 3.03–2.97 (m, 1H), 2.51–
2.43 (m, 1H), 2.34–2.26 (m, 1H), 0.99 (d, J¼7.0 Hz, 3H),
0.89 (d, J¼7.2 Hz, 3H); 13C NMR (150 MHz, CD3CN)
d 215.2, 162.6, 138.0, 127.2, 126.6, 126.3, 120.6, 119.4,
116.1, 110.4, 52.6, 48.9, 35.3, 27.7, 15.9, 7.9; HRMS
(ESI-TOF) calcd for C16H18BrNO4Na+ [M+Na+]
390.0311, found 390.0307.
4.5.30. Methyl 4-bromo-3-[3-(4-chlorophenyl)-2,2-di-
fluoro-3-oxopropyl]-1-hydroxy-1H-indole-2-carboxylate
(45). Rf¼0.31 (silica gel, EtOAc/hexanes, 2:8); IR (film)
1
nmax 1702, 1588, 1448, 1401, 1265, 1091, 762 cmꢁ1; H
NMR (500 MHz, CD3CN) d 9.24 (br s, 1H), 7.96 (d,
J¼8.8 Hz, 2H), 7.53–7.50 (m, 3H), 7.37 (d, J¼7.5 Hz,
1H), 7.23 (t, J¼8.8 Hz, 1H), 4.45 (t, J¼17.5 Hz, 2H), 3.82
(s, 3H); 13C NMR (125 MHz, CD3CN) d 189.0, 161.6,
140.8, 136.8, 132.0 (t, J¼3.6 Hz, 2C), 131.2, 129.5 (2C),
129.4, 128.5, 126.8, 126.7, 120.6, 115.4, 110.0, 108.3,
52.2, 29.3 (t, J¼23.8 Hz); HRMS (ESI-TOF) calcd for
C19H14BrClF2NO+4 [M+H+] 471.9757, found 471.9752.
4.5.26. Methyl 4-bromo-1-hydroxy-3-(3-oxo-3-phenyl-
propyl)-1H-indole-2-carboxylate (41). Rf¼0.35 (silica
gel, EtOAc/hexanes, 4:6); IR (film) nmax 3357, 2914, 1708,
1674, 1594, 1520, 1441, 1395, 1310, 1242, 1146, 1117,
1
771, 737, 686 cmꢁ1; H NMR (600 MHz, CD3CN) d 9.29
4.5.31. Methyl 4-bromo-3-(2,2-difluoro-3-oxo-3-thien-
2-ylpropyl)-1-hydroxy-1H-indole-2-carboxylate (46).
Rf¼0.25 (silica gel, EtOAc/hexanes, 4:6); IR (film) nmax
3335 (br), 3105, 2954, 1714, 1679, 1614, 1517, 1447,
1411, 1345, 1311, 1266, 1186, 1148, 1127, 1058, 932,
(br s, 1H), 7.99–7.94 (m, 2H), 7.60–7.55 (m, 1H), 7.49–
7.43 (m, 3H), 7.30 (br s, 1H), 7.18 (t, J¼7.7 Hz, 1H), 3.85
(s, 3H), 3.63 (br s, 2H), 3.35 (t, J¼7.7 Hz, 2H); 13C NMR
(150 MHz, CD3CN) d 200.1, 162.5, 137.8, 133.9, 129.5,
128.7, 128.6, 127.1, 126.2, 125.5, 121.0, 120.4, 116.0,
110.3, 52.5, 41.7, 20.2 (3C); HRMS (ESI-TOF) calcd for
C19H16BrNO4Na+ [M+Na+] 424.0155, found 424.0154.
1
879, 839, 761, 733 cmꢁ1; H NMR (500 MHz, CD3CN)
d 9.36 (br s, 1H), 7.95 (dd, J¼4.5, 1.3 Hz, 1H), 7.86–7.84
(m, 1H), 7.51 (d, J¼8.5 Hz, 1H), 7.38 (d, J¼7.0 Hz, 1H),
7.26–7.18 (m, 2H), 4.44 (t, J¼17.0 Hz, 2H), 3.84 (s, 3H);
13C NMR (125 MHz, CD3CN) d 183.8, 162.1, 139.3,
138.3, 137.2, 137.1 (t, J¼5.4 Hz), 130.1, 127.5, 127.3,
127.1, 121.1, 118.9, 115.9, 110.5, 108.8, 52.7, 30.0 (t, J¼
23.8 Hz); HRMS (ESI-TOF) calcd for C17H13BrF2NO4S+
[M+H+] 443.9711, found 443.9711.
4.5.27. Methyl 4-bromo-3-(4,4-dimethyl-3-oxopentyl)-1-
hydroxy-1H-indole-2-carboxylate (42). Rf¼0.46 (silica
gel, EtOAc/hexanes, 4:6); IR (film) nmax 3283, 2942, 2872,
1725, 1707, 1519, 1437, 1396, 1349, 1243, 1178, 1149,
1119, 984, 884, 779, 737 cmꢁ1 1H NMR (600 MHz,
;
CD3CN) d 9.34 (br s, 1H), 7.44 (br s, 1H), 7.29 (br s, 1H),
7.17 (t, J¼7.4 Hz, 1H), 3.90 (s, 3H), 3.40 (br s, 2H), 2.87
(t, J¼7.9 Hz, 2H), 1.09 (s, 9H); 13C NMR (150 MHz,
CD3CN) d 215.7, 162.6, 138.6, 127.2, 126.3, 124.8, 121.5,
120.5, 116.1, 110.3, 52.7, 44.6, 39.7, 26.6, 20.1 (3C);
HRMS (ESI-TOF) calcd for C17H20BrNO4Na+ [M+Na+]
404.0468, found 404.0456.
4.5.32. Methyl 4-bromo-1-hydroxy-3-(3-oxobutyl)-1H-
indole-2-carboxylate (47). Rf¼0.37 (silica gel, EtOAc/hex-
anes, 1:1); IR (film) nmax 3342, 2942, 1707, 1519, 1437, 1396,
1
1354, 1243, 1184, 1119, 879, 773, 737 cmꢁ1; H NMR
(400 MHz, CD3CN) d 9.36 (br s, 1H), 7.45 (d, J¼8.2 Hz,
1H), 7.30 (d, J¼8.2 Hz, 1H), 7.18 (t, J¼8.2 Hz, 1H), 3.91
(s, 3H), 3.44 (t, J¼8.0 Hz, 2H), 2.78 (t, J¼8.0 Hz, 2H),
2.11 (s, 3H); 13C NMR (125 MHz, CD3CN) d 208.7, 162.5,
137.9, 127.2, 126.3, 125.6, 121.1, 120.4, 116.0, 110.4,
4.5.28. Methyl 4-bromo-1-hydroxy-3-(2,2,4-trimethyl-3-
oxopentyl)-1H-indole-2-carboxylate (43). Rf¼0.45 (silica