Wynne and Stalick
1306, 1254, 1156, 1093, 1031, 969, 917, 839, 813 cm-1. 1H NMR
δ 7.82 (d, J ) 6, 2H), 7.50 (d, J ) 6, 2H), 7.40 (d, J ) 9, 1H),
7.15 (d, J ) 9, 2H), 6.93 (d, J ) 9, 1H), 6.97-6.69 (m, 2H),
6.40 (s, 1H), 5.80 (d, J ) 6, 2H), 5.47 (d, J ) 9, 1H), 4.20 (q, J
) 6, 2H), 3.75 (s, 2H), 3.72 (s, 3H), 2.31 (s, 3H), 0.99 (t, J ) 9,
3H), 0.87 (s, 9H), 0.48 (s, 6H). 13C NMR δ 169.5, 158.8, 142.6,
141.8, 137.7, 132.6, 130.0, 129.2, 128.4, 127.1, 121.5, 120.0,
119.5, 119.4, 118.0, 113.9, 113.6, 60.8, 58.5, 55.2, 54.6, 46.4,
26.2, 21.4, 19.3, 13.8. Anal. Calcd for C33H42N2O5SSi: C, 65.31;
H, 6.98; N, 4.62. Found: C, 65.67; H, 7.03; N, 4.34.
1H), 7.22 (s, 1H), 7.13 (t, J ) 9, 2H), 6.98 (t, J ) 6, 2H), 6.76
(d, J ) 6, 2H), 6.68 (s, 1H), 6.33 (d, J ) 9, 2H), 5.76 (d, J ) 6,
1H), 4.19 (q, J ) 3, 2H), 3.91 (s, 2H), 2.05 (s, 3H), 0.86 (t, J )
6, 3H), 0.79 (s, 9H), 0.42 (s, 6H). 13C NMR δ 186.7, 146.6, 142.0,
136.3, 131.5, 130.5, 130.3, 129.2, 128.1, 128.0, 126.0, 124.7,
121.9, 120.1, 120.1, 117.4, 114.0, 100.3, 96.3, 93.8, 50.7, 31.9,
29.7, 26.3, 21.2, 14.1. Anal. Calcd for C40H44N2O4SSi: C, 70.97;
H, 6.55; N, 4.14. Found: C, 71.36; H, 6.46; N, 3.83.
Gen er a l P r oced u r e. P r ep a r a tion of 5 fr om 4. Into a 50-
mL RB flask was placed a sample of compound 4 (8.42 mmol)
dissolved in 25 mL of freshly distilled THF. The solution was
allowed to stir under a positive flow of N2 for 15 min. To the
stirred solution was added 1.00 g of Bentonite K-10 clay. The
resulting solution was heated in an 80 °C oil bath for 12 h.
Upon completion, the reaction mixture was cooled, then diluted
with 20 mL of CH2Cl2 and vacuum filtered with the aid of a
Bu¨chner funnel to remove the clay from the reaction mixture.
The organic layer was dried over MgSO4 and concentrated
under reduced pressure. Final traces of solvent were removed
under vacuum for 4 h. Gradient flash column chromatography
(hexane:ethyl acetate) was performed to afford the desired
product 5.
[[[1-TBDMS-1H-in d ol-3-yl]-(4-ch lor o-p h en yl)-m eth yl]-
(tolu en e-4-su lfon yl)-a m in o]-a cetic a cid eth yl ester (4c):
A yellow oil, 63% yield. FTIR 3373, 3051, 2947, 2864, 1742,
1597, 1545, 1488, 1451, 1420, 1337, 1265, 1207, 1161, 1088,
1
1016, 969, 896, 839, 808, 740, 699 cm-1. H NMR δ 7.83 (d, J
) 9, 2H), 7.54 (d, J ) 9, 1H), 7.46-7.42 (m, 1H), 7.31 (d, J )
9, 2H), 7.24 (d, J ) 9, 2H), 7.18-6.88 (m, 4H), 6.69 (s, 1H),
6.43 (s, 1H), 5.83 (d, J ) 3, 1H), 3.82 (q, J ) 6, 2H), 2.42 (s,
3H), 2.36 (s, 2H), 1.01 (t, J ) 9, 3H), 0.88 (s, 9H), 0.50 (s, 6H).
13C NMR δ 156.2, 146.6, 142.0, 136.3, 131.5, 130.5, 130.3,
129.2, 128.2, 128.1, 128.0, 126.0, 124.7, 121.9, 120.1, 120.1,
117.4, 114.0, 50.7, 29.7, 26.2, 21.2, 19.3, 14.1. Anal. Calcd for
C
32H39ClN2O4SSi: C, 62.88; H, 6.43; N, 4.58. Found: C, 62.55;
1-P h en yl-2-(tolu en e-4-su lfon yl)-1,2,3,5-tetr a h yd r o-p y-
r id o[4,3-b]in d ol-4-on e (5a ): A brown oil, 61% yield. FTIR
3650, 3522, 3134, 3004, 3051, 2916, 1719, 1492, 1441, 1368,
H, 6.22; N, 4.88.
[[[1-TBDMS-1H-in d ol-3-yl]-p yr id in -2-yl-m eth yl]-(tolu -
en e-4-su lfon yl)-a m in o]-a cetic a cid eth yl ester (4d ):
A
1259, 1171, 1124, 1088, 989, 746, 678 cm-1 1H NMR δ
.
yellow powder, 61% yield, mp 87.5-93 °C. FTIR 3435, 3051,
8.18 (br s, 1NH), 7.78 (d, J ) 6, 2H), 7.62-7.40 (m, 2H), 7.31
(d, J ) 6, 2H), 7.17-7.02 (m, 7H), 4.97 (s, 1H), 4.32 (s, 1H),
2.35 (s, 3H). 13C NMR δ 185.6, 146.3, 141.6, 136.3, 134.6, 134.0,
133.8, 128.7 (overlapping peak), 127.8, 125.8, 124.9, 122.2,
121.8, 121.5, 119.7, 109.8, 51.7, 50.3, 22.4. Anal. Calcd for
2978, 1737, 1633, 1592, 1420, 1332, 1265, 1161, 1093, 1021,
1
896, 808, 740, 704 cm-1. H NMR δ 8.36 (d, J ) 6, 2H), 7.86
(d, J ) 6, 2H), 7.78-7.45 (m, 4H), 7.35 (d, J ) 6, 1H), 7.20-
6.78 (m, 3H), 6.78 (s, 1H), 5.78 (d, J ) 3, 1H), 4.01 (q, J ) 6,
2H), 2.43 (s, 3H), 2.32 (s, 2H), 1.13 (t, J ) 3, 3H), 0.75 (s, 9H),
0.45 (s, 6H). 13C NMR δ 169.3, 143.4, 141.5, 137.1, 133.3, 131.8,
129.4, 129.3, 128.6, 128.3, 128.0, 121.9, 119.9, 119.6, 117.3,
114.6, 113.9, 60.9, 58.3, 54.4, 54.3, 46.6, 26.1, 21.4, 19.2, 13.7.
Anal. Calcd for C31H39N3O4SSi: C, 64.44; H, 6.80; N, 7.27.
Found: C, 64.13; H, 7.12; N, 6.93.
C
24H20N2O3S: C, 69.21; H, 4.84; N, 6.73. Found: C, 68.97; H,
5.13; N, 6.49.
1-(4-Meth oxy-p h en yl)-2-(tolu en e-4-su lfon yl)-1,2,3,5-tet-
r a h yd r o-p yr id o[4,3-b]in d ol-4-on e (5b): Dark oil, 45% yield.
FTIR 3414, 3187, 3049, 2981, 2918, 1710, 1657, 1587, 1478,
1448, 1376, 1352, 1312, 1227, 1181, 1054, 1024, 1018, 998, 761
[[[1-TBDMS-1H-in d ol-3-yl]-(2-tr iflu or om eth yl-p h en yl)-
m eth yl]-(tolu en e-4-su lfon yl)-a m in o]-a cetic a cid eth yl es-
ter (4e): A yellow oil, 59% yield. FTIR 3269, 3051, 2937, 2854,
1742, 1597, 1550, 1493, 1467, 1451, 1420, 1337, 1311, 1239,
1
cm-1. H NMR δ 8.26 (br s, 1NH), 7.51 (d, J ) 6, 2H), 7.35 (d,
J ) 6, 2H), 7.21-7.15 (m, 3H), 7.07 (t, J ) 6, 1H), 7.04 (d, J
) 6, 1H), 6.89 (d, J ) 6, 1H), 6.81 (d, J ) 6, 2H), 5.07 (s, 1H),
4.05 (s, 2H), 3.77 (s, 3H), 1.55 (s, 3H). 13C NMR δ 158.9, 143.6,
142.9, 139.1, 137.6, 136.6, 132.5, 129.7, 129.2, 128.4, 127.2,
126.5, 125.4, 119.9, 119.4, 116.6, 113.7, 111.2, 55.2, 30.2, 29.7,
22.7. Anal. Calcd for C25H22N2O4S: C, 67.25; H, 4.97; N, 6.27.
Found: C, 67.04; H, 5.16; N, 6.19.
1213, 1161, 1119, 1036, 964, 927, 896, 808, 735, 709, 678 cm-1
.
1H NMR δ 7.82 (d, J ) 6, 2H), 7.75 (d, J ) 9, 2H), 7.59 (t, J )
6, 1H), 7.42 (t, J ) 6, 1H), 7.39-7.33 (m, 3H), 7.23 (d, J ) 6,
1H), 7.20-6.73 (m, 2H), 6.28 (s, 1H), 6.20 (d, J ) 3, 1H), 5.12
(d, J ) 3, 1H), 3.47 (q, J ) 6, 2H), 2.45 (s, 3H), 2.41 (s, 2H),
1.08 (t, J ) 9, 3H), 0.77 (s, 9H), 0.42 (s, 6H). 13C NMR δ 170.0,
168,7, 143.4, 141.7, 136.9, 131.7, 130.8, 129.7, 129.6, 129.5,
129.4, 129.0, 128.4, 127.4, 127.1, 122.1, 120.1, 118.6, 117.9,
114.1, 61.4, 55.1, 50.5, 48.3, 26.1, 21.5, 19.2, 14.1. Anal. Calcd
for C33H39F3N2O4SSi: C, 61.47; H, 6.10; N, 4.34. Found: C,
61.14; H, 5.86; N, 3.97.
1-(4-Ch lor o-p h en yl)-2-(t olu en e-4-su lfon yl)-1,2,3,5-t et -
r a h yd r o-p yr id o[4,3-b]in d ol-4-on e (5c): A brown oil, 57%.
FTIR 3352, 3097, 3081, 2975, 2961, 1719, 1643, 1602, 1302,
1
1156, 1093, 906, 813 cm-1. H NMR δ 8.46 (br s, 1NH), 7.79-
7.68 (m, 3H), 7.34-7.09 (m, 9H), 5.07 (s, 1H), 4.31 (s, 1H), 2.39
(s, 3H). 13C NMR δ 187.4, 146.7, 146.3, 142.3, 137.9, 135.9,
133.8, 130.3, 129.6, 129.1, 126.5, 125.2, 124.8, 122.6, 121.1,
120.8, 110.6, 52.3, 48.7, 23.1. Anal. Calcd for C24H19ClN2O3S:
C, 63.92; H, 4.25; N, 6.21. Found: C, 64.01; H, 4.52; N, 5.93.
[[[1-TBDMS-1H-in dol-3-yl]-th ioph en -2-yl-m eth yl]-(tolu -
en e-4-su lfon yl)-a m in o]-a cetic a cid eth yl ester (4f): A
brown powder, 43% yield, mp 87.5-93 °C. FTIR 3373, 3051,
2948, 2854, 2304, 1752, 1732, 1602, 1550, 1472, 1451, 1420,
1332, 1265, 1213, 1161, 1093, 1021, 964, 896, 839, 813, 740,
Gen er a l P r oced u r e. P r ep a r a tion of 8 fr om 4. Into a 50-
mL RB flask was placed a sample of compound 4 (8.42 mmol)
dissolved in 25 mL of freshly distilled THF. The solution was
allowed to stir under a positive flow of N2 for 15 min. To the
stirred solution was added 1.00 g of Bentonite K-10 clay. The
resulting solution was heated in an 80 °C oil bath for 12 h.
The reaction mixture was cooled and vacuum filtered with the
aid of a Bu¨chner funnel to remove the clay from the reaction
mixture. To the resulting combined organic layer was added
20 mL of THF, NaOH (16.84 mmol), and tetrabutylammonium
bromide (0.84 mmol). The solution was heated at reflux for 6
h, allowed to slowly cool to room temperature, diluted with
20 mL of CH2Cl2, and neutralized with 1 M HCl. The resulting
solution was washed with H2O (3 × 20 mL) and brine (1 × 15
mL). The organic layer was dried over MgSO4 and concen-
trated under reduced pressure. Final traces of solvent were
removed under vacuum for 4 h. Gradient flash column chro-
1
699, 668 cm-1. H NMR δ 7.83 (d, J ) 9, 1H), 7.55 (d, J ) 9,
2H), 7.41 (t, J ) 9, 1H), 7.26-6.98 (m, 3H), 6.97 (d, J ) 9,
2H), 6.97-6.89 (m, 2H), 6.68 (s, 1H), 6.09 (d, J ) 9, 1H), 4.11
(q, J ) 18, 2H), 2.38 (s, 2H), 2.32 (s, 3H), 0.91 (t, J ) 6, 3H),
0.86 (s, 9H), 0.54 (s, 6H). 13C NMR δ 169.3, 145.1, 142.7, 142.2,
141.6, 137.5, 129.8, 129.2, 129.0, 126.5, 125.7, 125.1, 121.8,
119.8, 119.7, 119.2, 117.4, 113.9, 60.8, 54.7, 51.1, 46.1, 26.1,
21.4, 19.2. Anal. Calcd for C30H38N2O4S2Si: C, 61.82; H, 6.57;
N, 4.81. Found: C, 61.71; H, 6.32; N, 5.18.
[[An t h r a ce n -9-yl-[1-TBDMS-1H -in d ol-3-yl]-m e t h yl]-
(tolu en e-4-su lfon yl)-a m in o]-a cetic a cid eth yl ester (4
g): A yellow oil, 61% yield. FTIR 3373, 3051, 2958, 2916, 2854,
1732, 1602, 1451, 1420, 1264, 1156, 1093, 1010, 964, 896, 839,
809, 735, 704 cm-1 1H NMR δ 8.17 (m, 2H), 7.86 (d, J ) 9,
.
2H), 7.54 (d, J ) 12, 2H), 7.43 (d, J ) 6, 1H), 7.36 (t, J ) 6,
4848 J . Org. Chem., Vol. 68, No. 12, 2003