6974
D. Z aꢀ rate-Z aꢀ rate et al. / Tetrahedron 71 (2015) 6961e6978
0
0
00
0
0
1
.0 Hz, 1H, H-5 ), 7.23 (ddd, J¼8.5, 7.0, 1.5 Hz, 1H, H-6 ), 7.30 (d,
(br t, J¼8.0 Hz, 1H, H-6 ), 7.31 (d, J¼8.0 Hz, 1H, H-7 ), 7.62 (d,
0
0
00
0
13
J¼8.5 Hz,1H, H-7 ), 7.63 (d, J¼8.0 Hz,1H, H-4 ), 8.12e8.16 (m, 2H, H-
J¼8.0 Hz, 1H, H-4 ), 8.14 (br s, 1H, NH). C NMR (125 MHz, CDCl
3
):
13
0
0
0
2
), 8.23e8.26 (m, 2H, H-3). C NMR (125 MHz, CDCl
3
):
d
¼26.6 (C-1 ),
d
¼25.8 (CH
3
CO), 29.5 (C-4), 77.1 (C-3),110.2 (C-3 ),111.2 (C-7 ),118.6
0
00
0
00
00
0
0
0
0
0
27.2 (CH
3
CO), 48.6 (C-1 ), 80.0 (C-2 ),108.5 (C-3 ),109.8 (C-7 ),117.2
(C-4 ), 119.5 (C-5 ), 122.1 (C-6 ), 122.9 (C-2 ), 127.4 (C-3a ), 136.1 (C-
0
00
00
00
00
0
þ
(
2
1
C
C-3 ), 118.8 (C-4 ), 119.4 (C-5 ), 122.1 (C-6 ), 123.5 (C-3), 126.6 (C-
7a ), 209.9 (CH
3
CO). MS (70 eV): m/z (%)¼203 (M , 6), 160 (1), 144
0
0
00
000
00
þ
),127.9 (C-3a ),131.0 (C-2),133.3 (C-2 ),134.8 (C-1),136.4 (C-7a ),
), 204.7 (CH CO). Anal. Calcd for
22 20 2 5
H N O : C, 67.34; H, 5.14; N, 7.14. Found: C, 67.32; H, 5.17; N, 7.14.
(8), 131 (12), 130 (100), 103 (6), 77 (4). HRMS (EI) m/z [M ] calcd for
50.7 (C-4), 164.2 (ArCO
2
3
C
12
H13NO
2
: 203.0946. Found: 203.0939.
4
.8.2. 4-(1-Allyl-1H-indol-3-yl)-3-hydroxybutan-2-one
4
.7.3. 3-Oxo-1-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)butan-2-yl 4-
(24b). According to the general procedure, by using 26b (0.060 g,
0.15 mmol) and K CO (0.043 g, 0.31 mmol), 24b (0.026 g, 70%) was
obtained as a pale yellow oil: R 0.44 (hexane/EtOAc, 7:3). IR (film):
¼3449, 2918, 1712, 1613, 1467, 1437, 1419, 1356, 1187, 1088, 1014,
nitrobenzoate (26c). According to the general procedure, by using
1
5
2
3
a (0.500 g, 2.13 mmol), 23c (0.300 g,1.94 mmol), and ZnCl
2
(0.792 g,
f
.82 mmol), 26c (0.620 g, 82%) was obtained as a yellow solid: R
f
0.40
n
ꢀ
ꢂ1 1
(
hexane/EtOAc, 7:3); mp 88e89 C. IR (film):
n
¼3285, 2124, 1721,
991, 926, 741 cm . H NMR (300 MHz, CDCl
3
):
d¼2.19 (s, 3H, CH
3
CO),
1607, 1527, 1467, 1349, 1276, 1182, 1117, 1103, 1014, 872, 844, 743,
3.12 (ddd, J¼15.0, 6.6, 0.5 Hz, 1H, H-4), 3.30 (ddd, J¼15.0, 4.8, 0.9 Hz,
ꢂ1 1
719 cm . H NMR (500 MHz, CDCl
3
):
d
¼2.15 (s, 3H, CH
3
CO), 2.38 (t,
1H, H-4), 3.49 (br d, J¼5.0 Hz, 1H, OH), 4.47e4.54 (m, 1H, H-3), 4.68
0
00
0
00
00
J¼3.3 Hz,1H, H-3 ), 3.36e3.46 (m, 2H, H-1 ), 4.83 (d, J¼3.3 Hz, 2H, H-
(dt, J¼5.4, 1.7 Hz, 2H, H-1 ), 5.04 (ddt, J¼17.1, 2.9, 1.7 Hz, 1H, H-3 ),
0
00
0
00
00
1
), 5.55 (dd, J¼7.0, 5.5 Hz,1H, H-2 ), 7.11 (s,1H, H-2 ), 7.16 (td, J¼8.0,
5.18 (ddt, J¼10.2, 2.9, 1.7 Hz, 1H, H-3 ), 5.96 (ddt, J¼17.1, 10.2, 5.4 Hz,
0
0
00
00
0
0
0
1
1
8
2
.0 Hz, 1H, H-5 ), 7.27 (td, J¼8.0, 1.0 Hz, 1H, H-6 ), 7.38 (d, J¼8.0 Hz,
1H, H-2 ), 7.02 (s, 1H, H-2 ), 7.12 (ddd, J¼7.8, 6.9, 1.2 Hz, 1H, H-5 ),
0
0
00
0
H, H-7 ), 7.64 (d, J¼8.0 Hz, 1H, H-4 ), 8.12e8.16 (m, 2H, H-2),
7.21 (ddd, J¼8.1, 6.9, 1.2 Hz, 1H, H-6 ), 7.29 (br d, J¼8.1 Hz, 1H, H-7 ),
13
13
0
0
.22e8.26 (m, 2H, H-3). C NMR (125 MHz, CDCl
3
):
d
¼26.5 (C-1 ),
7.62 (dd, J¼7.8, 1.1 Hz, 1H, H-4 ). C NMR (75 MHz, CDCl
3
):
d
¼25.8
0
00
000
000
0
00
0
0
7.1 (CH
3
CO), 35.7 (C-1 ), 73.6 (C-3 ), 77.5 (C-2 ), 79.9 (C-2 ), 109.3
(CH
3
CO), 29.5 (C-4), 48.7 (C-1 ), 77.1 (C-3), 109.1 (C-3 ), 109.7 (C-7 ),
0
0
00
00
00
00
00 0 0 0 0
(
C-3 ), 109.6 (C-7 ), 119.0 (C-4 ), 119.9 (C-5 ), 122.4 (C-6 ), 123.5 (C-
117.2 (C-3 ), 118.8 (C-4 ), 119.2 (C-5 ), 121.7 (C-6 ), 126.6 (C-2 ), 128.0
0
0
00
00
0
00
0
3
), 126.0 (C-2 ), 128.2 (C-3a ), 131.1 (C-2), 134.7 (C-1), 136.0 (C-7a ),
), 204.6 (CH CO). Anal. Calcd for
: C, 67.69; H, 4.65; N, 7.18. Found: C, 67.70; H, 4.63; N, 7.16.
(C-3a ), 133.3 (C-2 ), 136.2 (C-7a ), 209.8 (CH
3
CO). HRMS (EI) m/z
þ
150.7 (C-4), 164.2 (ArCO
2
3
[M ꢂOH] calcd for C15
H16NO: 226.1232. Found: 226.1231.
C
22 18 2 5
H N O
4
.8.3. 3-Hydroxy-4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)butan-2-one
(24c). According to the general procedure, by using 26c (0.290 g,
0.744 mmol) and K CO (0.308 g, 2.23 mmol), 24c (0.11 g, 61%) was
obtained as a pale yellow oil: R 0.32 (hexane/EtOAc, 7:3). IR (film):
¼3462, 3282, 1711, 1466, 1356, 1185, 1086, 743 cm
(500 MHz, CDCl ):
4
.7.4. 1-(1-(3-Methoxybenzyl)-1H-indol-3-yl)-3-oxobutan-2-yl 4-
nitrobenzoate (26d). According to the general procedure, by using
a (0.632 g, 2.69 mmol), 23d (0.578 g, 2.45 mmol), and ZnCl
2
3
1
2
f
ꢂ1
1
(
1.000 g, 7.35 mmol), 26d (0.851 g, 74%) was obtained as a yellow
n
. H NMR
ꢀ
solid: R
f
0.46 (hexane/EtOAc, 7:3); mp 150e151 C. IR (film):
n
¼1719,
3
d
¼2.17 (s, 3H, CH CO), 2.37 (t, J¼2.5 Hz, 1H, H-
3
0
0
1602, 1525, 1490, 1466, 1437, 1347, 1266, 1167, 1102, 1041, 1013, 871,
3 ), 3.07 (ddd, J¼15.0, 6.5, 1.0 Hz, 1H, H-4), 3.27 (ddd, J¼15.0, 4.5,
1.0 Hz, 1H, H-4), 3.46 (d, J¼5.0 Hz, 1H, OH), 4.45e4.49 (m, 1H, H-3),
ꢂ1 1
8
CH
CH
43, 781, 743, 718 cm . H NMR (300 MHz, CDCl
3
):
d
¼2.13 (s, 3H,
0
00
0
3
CO), 3.33e3.49 (m, 2H, H-1 ), 3.67 (s, 3H, CH
3
O), 5.20 (s, 2H,
4.79 (d, J¼2.5 Hz, 1H, H-1 ), 7.11 (s, 1H, H-2 ), 7.14 (ddd, J¼8.0, 7.0,
0
000
0
0
2
eN), 5.55 (dd, J¼7.2, 5.7 Hz, 1H, H-2 ), 6.56e6.60 (m, 1H, H-2 ),
1.0 Hz, 1H, H-5 ), 7.24 (ddd, J¼8.5, 7.0, 1.5 Hz, 1H, H-6 ), 7.35 (br d,
13
000
000
0
0
6
.63 (br d, J¼7.5 Hz,1H, H-6 ), 6.75 (dd, J¼8.1, 2.4 Hz,1H, H-4 ), 7.00
J¼8.5 Hz, 1H, H-7 ), 7.62 (dt, J¼8.0, 1.5 Hz, 1H, H-4 ). C NMR
0
0
00
00
000
00
(
s, 1H, H-2 ), 7.09e7.23 (m, 3H, H-5 , H-6 , H-5 ), 7.28 (br d,
(125 MHz, CDCl
3
):
d
¼25.8 (CH
3
CO), 29.5 (C-4), 35.6 (C-1 ), 73.5 (C-
0
0
00
00
00
0
0
0
J¼7.8 Hz, 1H, H-7 ), 7.63 (dd, J¼7.6, 0.6 Hz, 1H, H-4 ), 8.04e8.09 (m,
3 ), 77.1 (C-3), 77.7 (C-2 ), 109.4 (C-7 ), 110.0 (C-3 ), 119.0 (C-4 ),
1
3
0
0
0
0
0
2
H, H-2), 8.13e8.19 (m, 2H, H-3). C NMR (75 MHz, CDCl
3
):
d
¼26.5
119.7 (C-5 ), 122.1 (C-6 ), 126.0 (C-2 ), 128.4 (C-3a ), 135.9 (C-7a ),
209.6 (CH CO). Anal. Calcd for C15 : C, 74.67; H, 6.27; N, 5.81.
Found: C, 74.71; H, 6.23; N, 5.86.
0
0
(
C-1 ), 27.0 (CH
3
CO), 49.7 (CH
2
000
eN), 55.0 (CH
3
O), 79.7 (C-2 ),108.7 (C-
3
H15NO
2
0
0
0
00
00
000
00
3
6
), 109.8 (C-7 ), 112.4 (C-4 ), 112.8 (C-2 ), 118.7 (C-4 ), 118.9 (C-
),119.4 (C-5 ),122.1 (C-6 ),123.4 (C-3),126.9 (C-2 ),127.8 (C-3a ),
00
00
00
00
000
0
00
00
129.7 (C-5 ), 130.8 (C-2), 134.6 (C-1), 136.5 (C-7a ), 138.8 (C-1 ),
4.8.4. 3-Hydroxy-4-(1-(3-methoxybenzyl)-1H-indol-3-yl)butan-2-
one (24d). According to the general procedure, by using 26d
0
00
150.5 (C-4), 159.8 (C-3 ), 164.1 (ArCO
2
), 204.6 (CH
: 472.1634. Found: 472.1643.
3
CO). HRMS (EI)
þ
m/z [M ] calcd for C27
H
24
N
2
O
6
(0.120 g, 0.254 mmol) and K
2
CO
3
(0.070 g, 0.51 mmol), 24d (0.078 g,
0.38 (hexane/EtOAc, 7:3
95%) was obtained as a pale yellow oil: R
f
4
.8. General procedure for the preparation of 24aed
(ꢁ2)). IR (film):
n
¼3459, 2921, 1711, 1601, 1489, 1465, 1436, 1353,
ꢂ1 1
1
262, 1150, 1085, 1044, 779, 741 cm . H NMR (300 MHz, CDCl ):
3
A mixture of 26 (1.0 mol equiv) and K
in THF/MeOH (1:1) (20 mL) was stirred at room temperature for
0 min. Afterward a saturated aqueous solution of NH Cl (10 mL)
was added, then extracted with EtOAc (2ꢁ10 mL). The organic layer
SO ), and the
2
CO
3
(2.0e3.0 mol equiv)
d
¼2.16 (s, 3H, CH
3
CO), 3.11 (dd, J¼15.3, 6.6 Hz, 1H, H-4), 3.29 (dd,
O),
4.44e4.53 (m,1H, H-3), 5.21 (s, 2H, H-1 ), 6.60 (br s, 1H, H-2 ), 6.65
J¼15.3, 4.8 Hz, 1H, H-4), 3.49 (br s, 1H, OH), 3.71 (s, 3H, CH
3
0
0
000
3
4
0
00
000
(br d, J¼7.8 Hz, 1H, H-6 ), 6.77 (dd, J¼8.3, 2.1 Hz, 1H, H-4 ), 7.04 (s,
0
0
0
0
000
was washed with water (2ꢁ10 mL) and dried (Na
2
4
1H, H-2 ), 7.06e7.26 (m, 4H, H-5 , H-6 , H-7 , H-5 ), 7.63 (dd, J¼6.6,
0
13
solvent was removed under vacuum. The residue was purified by
column chromatography on silica gel (20 g/g crude, hexane/EtOAc,
1.2 Hz, 1H, H-4 ). C NMR (75 MHz, CDCl
3
):
d
¼25.8 (CH
3
CO), 29.5
0
0
0
(CH
2
-4), 49.8 (C-1 ), 55.1 (CH
3
O), 77.1 (C-3), 109.4 (C-3 ), 109.7 (C-
0
000
000
0
000
0
9
:1) to give the desired products 24aed.
7 ), 112.4 (C-2 ), 112.7 (C-4 ), 118.8 (C-4 ), 118.9 (C-6 ), 119.3 (C-5 ),
1
139.0 (C-1 ), 159.8 (C-3 ), 209.7 (CH
calcd for C20H21NO : 323.1521. Found: 323.1513.
0
0
0
000
0
21.9 (C-6 ), 127.0 (C-2 ), 128.1 (C-3a ), 129.7 (C-5 ), 136.4 (C-7a ),
0
00
000
þ
4.8.1. 3-Hydroxy-4-(1H-indol-3-yl)butan-2-one (actinopolymorphol
3
CO). HRMS (EI) m/z [M ꢂOH]
B) (24a). According to the general procedure, by using 26a (0.450 g,
.28 mmol) and K CO (0.353 g, 2.56 mmol), 24a (0.23 g, 89%) was
obtained as a pale yellow oil: R
3
1
2
3
f
0.22 (hexane/EtOAc, 7:3). IR (film):
4.9. 1-(1H-Indol-3-yl)-3-methylbutane-2,3-diol (tanakine)
(25)
ꢂ1 1
n
¼3406, 1709, 1618, 1457, 1425, 1355, 1244, 1093, 743 cm . H NMR
(
500 MHz, CDCl
3
):
d
¼2.17 (s, 3H, CH CO), 3.10 (dd, J¼15.0, 6.5 Hz,
3
1
(
H, H-4), 3.29 (dd, J¼15.0, 3.0 Hz, 1H, H-4), 3.48 (br s, 1H, OH), 4.50
To a solution of 24a (0.100 g, 0.49 mmol) in anhydrous THF
0
0
ꢀ
br s, 1H, H-3), 7.04 (s, 1H, H-2 ), 7.12 (br t, J¼8.0 Hz, 1H, H-5 ), 7.18
(3 mL) at 0 C a 3.0 M Et
2
O solution of MeMgBr (0.293 g, 2.46 mmol)