Page 13 of 24
The Journal of Organic Chemistry
1
(
2S,2aS,2a R,3aR,5S,7S,8bR,10aR)-2-methyl-7-(prop-1-en-
J = 12.2, 6.3, 2.3 Hz, 1H), 1.79–1.69 (m, 4H), 1.40 (ddd, J =
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2-yl)-5-((triethylsilyl)oxy)-2-((trimethylsilyl)oxy)-
13.5, 12.4, 10.3 Hz, 1H), 1.34 (s, 3H), 0.92 (s, 9H), 0.13 (s, 3H),
0.11 (s, 3H); C{ H} NMR (CDCl , 101 MHz) δ 173.9, 148.6,
3
1
13
1
1
,2a ,3a,4,5,6,7,8,8b,10a-
decahydrobenzo[6,7]oxireno[2',3':3a,4]azuleno[1,8-bc]furan-
130.5, 126.5, 109.4, 79.7, 75.3, 75.0, 70.5, 55.8, 48.9, 45.8, 44.3,
38.7, 38.5, 37.4, 28.6, 26.6, 26.2, 20.9, 18.4, –3.5, –4.6; IR (Neat
Film, NaCl) 3465, 2930, 2857, 1771, 1463, 1370, 1256, 1140,
9
0
(2H)-one (26). To a stirred solution of allylic alcohol 25 (5 mg,
.012 mmol, 1.00 equiv) in CH Cl (0.3 mL) at –78 °C (i-
N (35 ml, 0.25 mmol, 20.8
2
2
–1
PrOH/dry ice bath) was added Et
3
1102, 1056, 988, 972, 883, 836, 774 cm ; HRMS (FAB+) m/z
+
equiv) dropwise. After 5 minutes, TESOTf (15 mL, 0.060 mmol,
5.00 equiv) was added slowly dropwise. After an additional 20
minutes, the consumption of starting material was complete as
determined by TLC (1:1 EtOAc:Hexanes eluent). The reaction
calc’d for
[α]D +87.5 ° (c 0.400, CHCl3).
C
25
H
39
O
5
Si [M+H] :447.2567, found 447.2552;
2
5.0
Unsaturated Lactone 31: R = 0.29 (3:17 Acetone:Hexanes
f
1
eluent); H NMR (CDCl , 400 MHz) δ 4.80 (ddd, J = 9.3, 7.8,
3
was quenched by the addition of saturated aqueous NaHCO
3
(80
7.2 Hz, 1H), 4.75 (dt, J = 1.8, 0.9 Hz, 1H), 4.73 (s, 1H), 4.16–
4.07 (m, 1H), 3.88 (ddd, J = 10.1, 9.0, 4.3 Hz, 1H), 3.81 (dt, J =
9.3, 2.5 Hz, 1H), 3.37 (ddd, J = 5.4, 2.0, 0.7 Hz, 1H), 2.61–2.51
(m, 2H), 2.41 (dtd, J = 9.3, 4.7, 2.4 Hz, 1H), 2.38–2.32 (m, 1H),
2.14 (tt, J = 11.7, 4.1 Hz, 1H), 2.08–1.97 (m, 2H), 1.97–1.90 (m,
1H), 1.86 (ddd, J = 13.7, 11.1, 2.5 Hz, 1H), 1.74 (dd, J = 1.5, 0.8
Hz, 3H), 1.43 (td, J = 12.5, 10.2 Hz, 1H), 1.32 (d, J = 0.9 Hz,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
mL), removed from the cooling bath, and allowed to warm to
ambient temperature (ca. 23 °C). The reaction mixture was then
filtered through a silica gel plug, eluting with EtOAc. The com-
bined organics were concentrated in vacuo. The crude white sol-
id was purified by silica gel column chromatography (10%
EtOAc in hexanes eluent) to afford bis-silyl ether 26 (4 mg, 66%
1
3
1
yield) as an amorphous white solid:
R
f
=
0.14 (1:9
, 600 MHz) δ 4.84–
.72 (m, 2H), 4.70 (s, 1H), 4.33–4.21 (m, 1H), 3.25 (dd, J = 6.4,
.7 Hz, 1H), 3.20 (d, J = 5.4 Hz, 1H), 3.10 (d, J = 6.4 Hz, 1H),
3H), 0.93 (s, 9H), 0.13 (s, 3H), 0.12 (s, 3H); C{ H} NMR
1
EtOAc:Hexanes eluent); H NMR (CDCl
3
(CDCl , 101 MHz) δ 169.7, 158.8, 148.2, 116.1, 109.6, 74.5,
3
4
4
73.5, 73.3, 70.9, 54.3, 51.6, 48.1, 41.5, 41.0, 40.4, 32.6, 26.0,
23.5, 22.7, 20.6, 18.2, –3.9, –4.7; IR (Neat Film, NaCl) 3494,
2929, 2857, 1742, 1645, 1455, 1360, 1259, 1176, 1121, 1078,
2.93–2.84 (m, 2H), 2.65 (dd, J = 19.5, 5.5 Hz, 1H), 2.41–2.32
(m, 2H), 2.28 (dd, J = 15.0, 6.5 Hz, 1H), 2.10–2.03 (m, 1H),
–
1
1053, 957, 918, 898, 837, 775 cm ; HRMS (FAB+) m/z calc’d
+
25.0
1
0
.76–1.70 (m, 4H), 1.41 (td, J = 12.7, 10.0 Hz, 1H), 1.31 (s, 3H),
25 39 5 D
for C H O Si [M+H] : 447.2567, found 447.2577; [α]
.93 (t, J = 7.9 Hz, 9H), 0.68–0.54 (m, 6H), 0.18 (s, 9H);
+56.1° (c 0.600, CHCl3).
1
3
1
C{ H} NMR (CDCl
3
, 126 MHz) δ 173.7, 148.6, 130.0, 127.0,
HO
1
3
2
09.3, 79.3, 77.0, 74.9, 69.6, 53.8, 48.6, 44.5, 43.4, 38.6, 38.5,
7.2, 29.7, 28.7, 20.8, 7.2, 6.5, 0.6; IR (Neat Film, NaCl) 3464,
956, 1766, 1665, 1451, 1376, 1249, 1143, 1047, 890, 841, 795,
H
O
H
OH
–
1
+
47 5 2
744 cm ; HRMS (FAB+) m/z calc’d for C28H O Si [M+H] :
519.2962, found 519.2959; [α]
O
O
H
2
5.0
D
+53.6° (c 0.100, CHCl
3
).
32
TBSO
TBSO
H
1
(2S,2aS,2a R,3aR,4aS,5S,7S,10aR)-2,5-dihydroxy-2-
O
H
OH
O
H
OH
1
methyl-7-(prop-1-en-2-yl)-1,2a ,3a,4,4a,5,6,7,8,10a-
decahydrobenzo[6,7]oxireno[2',3':3a,4]azuleno[1,8-bc]furan-
9(2H)-one (32). To a stirred solution of silyl ether 31 (4 mg,
0.009 mmol, 1.00 equiv) in THF (0.6 mL) at –78 °C (i-PrOH/dry
ice bath) was added TBAF (11 mL, 1 M in THF, 1.22 equiv)
slowly dropwise. After 3 h, the reaction was introduced to a 0 °C
O
O
H
O
O
H
30
31
1
(
2S,2aS,2a R,3aR,5S,7S,8bR,10aR)-5-((tert-
butyldimethylsilyl)oxy)-2-hydroxy-2-methyl-7-(prop-1-en-2-
bath (ice/H O). After a further 4 h, the consumption of starting
2
1
yl)-1,2a ,3a,4,5,6,7,8,8b,10a-
material was complete as determined by TLC (1:4 Ace-
decahydrobenzo[6,7]oxireno[2',3':3a,4]azuleno[1,8-bc]furan-
tone:Hexanes eluent). The reaction was removed from the cool-
ing bath and immediately concentrated in vacuo. The crude dark
brown oil was purified by silica gel column chromatography
1
9
(2H)-one (30) and (2S,2aS,2a R,3aR,4aS,5S,7S,10aR)-5-
(
(tert-butyldimethylsilyl)oxy)-2-hydroxy-2-methyl-7-(prop-1-
1
en-2-yl)-1,2a ,3a,4,4a,5,6,7,8,10a-
(EtOAc eluent) to provide epoxide 32 (3 mg, >99% yield) as an
1
decahydrobenzo[6,7]oxireno[2',3':3a,4]azuleno[1,8-bc]furan-
amorphous white solid: R = 0.31 (EtOAc eluent); H NMR
f
9
(2H)-one (31). To a stirred solution of allylic alcohol 24 (65
mg, 0.20 mmol, 1.00 equiv) in CH Cl (20 mL) were added im-
idazole (2.72 g, 40.0 mmol, 200.0 equiv) and DMAP (98 mg,
.80 mmol, 4.00 equiv) as solids sequential, each in a single por-
(CDCl , 400 MHz) δ 4.83 (dt, J = 9.2, 7.4 Hz, 1H), 4.77 (dt, J =
3
2
2
1.7, 0.9 Hz, 1H), 4.75 (q, J = 1.5 Hz, 1H), 3.96 (dd, J = 14.0, 4.7
Hz, 1H), 3.93–3.86 (m, 1H), 3.84 (dt, J = 9.2, 2.5 Hz, 1H), 3.43
(dd, J = 4.8, 2.2 Hz, 1H), 2.63–2.52 (m, 2H), 2.42 (dddd, J = 8.3,
6.2, 4.3, 2.2 Hz, 1H), 2.32 (bs, 1H), 2.26–2.03 (m, 4H), 1.93 (dd,
J = 13.3, 7.3 Hz, 1H), 1.75 (t, J = 1.1 Hz, 3H), 1.44 (ddd, J =
0
tion. After 5 minutes, to the resulting homogenous, pale yellow
solution was added TBSCl (3.01 g, 20.0 mmol, 100.0 equiv) as a
1
3
1
solution in CH
2
Cl
2
(7.5 mL) quickly dropwise over 5 minutes.
12.4, 11.7, 10.5 Hz, 1H), 1.33 (t, J = 0.8 Hz, 3H); C{ H} NMR
After 17 h, the consumption of starting material was complete as
determined by TLC (19:1 EtOAc:Hexanes eluent). The reaction
(CDCl , 101 MHz) δ 169.6, 158.0, 148.0, 116.9, 109.8, 74.6,
3
73.5, 72.7, 70.4, 54.3, 50.8, 48.0, 41.6, 40.8, 40.1, 31.9, 23.5,
®
mixture was then filtered through a Celite plug, washing with
23.0, 20.8; IR (Neat Film, NaCl) 3418, 2964, 2925, 2855, 1732,
1644, 1446, 1372, 1260, 1177, 1103, 1048, 1029, 911, 802, 732
2 2
CH Cl eluent. The combined organics were concentrated in
–1
+
vacuo and purified by silica gel column chromatography (15%
acetone in hexanes eluent) to furnish diol allylic silyl ether 30
(23 mg, 26% yield) as an amorphous white solid and unsaturated
lactone 31 (66 mg, 74% yield) as an amorphous white solid.
19 25 5
cm ; HRMS (FAB+) m/z calc’d for C H O [M+H] :
2
5.0
333.1702, found 333.1688; [α]D +14.3° (c 0.150, CHCl3).
O
O
H
OH
Allylic Silyl Ether 30: R
f
= 0.20 (3:17 Acetone:Hexanes elu-
1
ent); H NMR (CDCl
3
, 400 MHz) δ 4.78–4.67 (m, 3H), 4.26 (bt,
J = 8.0 Hz, 1H), 3.35 (dd, J = 6.1, 4.5 Hz, 1H), 3.31 (d, J = 5.4
Hz, 1H), 3.17 (dd, J = 5.8, 1.9 Hz, 1H), 2.97–2.78 (m, 2H),
O
O
H
ent-Isoineleganolide A (13)
2
.78–2.67 (m, 1H), 2.55 (bs, 1H), 2.42–2.24 (m, 3H), 2.06 (ddt,
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