The Journal of Organic Chemistry
Article
−
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6
(
67 cm . HRMS (FAB-double focusing magnetic sector) C H NO
2857, 1691, 1680, 1254, 1110, 837, 778 cm . HRMS (ESI-TOF)
22 42 5 4 2
12
18
+
+
+
M + H) calcd 192.1388, found 192.1391.
Preparation of 13. Compound 12 (59.8 mg, 0.1 mmol) and 11
C H N O Si (M + H) calcd 496.2775, found 496.2768.
Preparation of Bis-silylated 7b. NaH (60% in mineral oil, 28 mg,
39
(
46 mg, 0.24 mmol) were stirred in THF (1 mL) at room temperature
0.7 mmol) was slowly added to 18 (335 mg, 0.7 mmol) in DMF
(7 mL). The reaction was stirred at 0 °C for 1 h, at which time 21
(290 mg, 1.4 mmol) was added at 0 °C. The reaction was stirred at
room temperature for 4 h, concentrated under vacuum, and purified by
flash chromatography on a silica column. Elution with 50% EtOAc in
overnight. The reaction was concentrated under vacuum and purified
by flash chromatography on a silica column. Elution with 3% MeOH
in DCM gave 13 as a white solid (53.9 mg, 83%). Mp 78−79 °C; H
NMR (400 MHz, CDCl ) δ 8.33 (s, 1H), 8.04 (s, 1H), 7.34−7.26 (m,
1
3
1
2
6
3
1
H), 7.24 (dd, J = 5.1, 3.7 Hz, 1H), 7.18−7.12 (m, 2H), 6.42 (t, J =
.5 Hz, 1H), 4.65−4.57 (m, 1H), 4.00 (dd, J = 7.5, 3.3 Hz, 1H), 3.90−
.67 (m, 6H), 2.69−2.54 (m, 1H), 2.41 (ddd, J = 13.0, 6.1, 3.8 Hz,
H), 1.32 (s, 6H), 0.91 (s, 9H), 0.91 (s, 9H), 0.09 (s, 6H), 0.08
hexanes gave bis-silylated 7b as a yellow foam (320 mg, 74%). H
NMR (400 MHz, MeOH-d ) δ 7.94 (s, 1H), 7.62 (s, 1H), 6.28 (t, J =
4
6.4 Hz, 1H), 4.69 (dd, J = 9.2, 3.9 Hz, 1H), 3.95 (dd, J = 7.7, 3.7 Hz,
1H), 3.84 (dd, J = 11.2, 4.5 Hz, 1H), 3.76 (dd, J = 11.2, 3.6 Hz, 1H),
2.73 (dt, J = 12.6, 6.1 Hz, 1H), 2.40 (ddd, J = 13.2, 6.3, 4.3 Hz, 1H),
1.48 (s, 6H), 1.25 (s, 9H), 0.93 (s, 9H), 0.88 (s, 9H), 0.14 (s, 6H),
0.07 (s, 3H), 0.04 (s, 3H). 13C NMR (101 MHz, MeOD) δ 218.4,
144.1, 140.5, 136.5, 118.8, 87.9, 87.2, 84.2, 71.9, 62.4, 43.8, 40.2, 27.9,
25.1, 24.91, 23.8, 17.9, 17.5, −5.9, −6.0, −6.8. IR (KBr plate) 2927,
(
s, 3H), 0.08 (s, 3H). 13C NMR (75 MHz, CDCl ) δ 212.2, 155.1,
3
1
4
52.8, 150.6, 138.2, 134.3, 129.6, 128.4, 126.8, 87.8, 84.2, 71.9, 62.8,
9.6, 43.7, 41.2, 26.0, 25.8, 22.6, 18.4, 18.0, −4.7, −4.8, −5.4, −5.5. IR
(
KBr plate) 2953, 2928, 2855, 1708, 1613, 1471, 1252, 835, 777,
−1
+
+
7
6
24 cm ; HRMS (ESI-TOF) C H N O Si (M + H) calcd
34 56 5 4 2
−1
54.3871, found 654.3871.
Preparation of 7a. Et N·3HF (161 mg, 1.0 mmol) was slowly
1672, 1609, 1474, 1254, 1112, 832, 782, 662 cm . HRMS (ESI-TOF)
+
+
C H N O Si (M + H) calcd 622.3820, found 622.3820.
3
30 56
5
5
2
added to 13 (65 mg, 0.1 mmol) in THF (1 mL). The reaction was
stirred at 25 °C overnight. The reaction was concentrated under
vacuum and purified by flash chromatography on a silica column.
Elution with 5% MeOH in DCM gave 7a as a white solid (37.0 mg,
8
Preparation of 7b. Et N·3HF (0.83 g, 5.2 mmol) was slowly added
3
to bis-silylated 7b (320 mg, 0.52 mmol), and the reaction was stirred at
25 °C overnight. The reaction was concentrated under vacuum and
purified by flash chromatography on a silica column. Elution with 5%
1
1
7%). Mp 104−106 °C; H NMR (400 MHz, MeOH-d ) δ 8.29
MeOH in DCM gave 7b as a yellow foam (163 mg, 59%). H NMR
4
(
s, 1H), 8.23 (s, 1H), 7.34−7.03 (m, 5H), 6.43 (dd, J = 7.8, 6.0 Hz,
(400 MHz, MeOH-d ) δ 8.01 (s, 1H), 7.64 (s, 1H), 6.45−6.17 (m,
4
1
3
3
H), 4.65−4.56 (m, 1H), 4.09 (dd, J = 5.5, 2.9 Hz, 1H), 3.97 (s, 2H),
.86 (dd, J = 12.3, 2.9 Hz, 2H), 3.75 (dd, J = 12.3, 3.3 Hz, 1H), 3.43−
.10 (m, 2H), 2.81 (ddd, J = 13.6, 8.0, 5.8 Hz, 1H), 2.41 (ddd,
1H), 4.60−4.40 (m, 1H), 4.02 (dd, J = 6.1, 3.2 Hz, 1H), 3.80 (dd, J =
12.2, 3.2 Hz, 1H), 3.75−3.67 (m, 1H), 2.77−2.62 (m, 1H), 2.39 (ddd,
1
3
J = 13.4, 6.0, 2.9 Hz, 1H), 1.48 (s, 6H), 1.24 (s, 9H). C NMR
13
J = 13.4, 6.0, 2.6 Hz, 1H), 1.32 (s, 6H). C NMR (101 MHz,
(101 MHz, MeOH-d ) δ 218.4, 144.2, 140.5, 140.3, 137.1, 119.2, 88.3,
4
MeOH-d ) δ 211.1, 153.6, 150.5, 138.2, 133.3, 129.5, 127.9, 126.9,
87.3, 85.3, 71.4, 62.1, 43.8, 40.6, 27.9, 23.8. IR (KBr plate) 3278
4
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126.3, 124.6, 87.0, 84.3, 70.2, 60.8, 48.0, 41.9, 38.7, 27.8, 20.0. IR
(broad), 2932, 1669, 1610, 1471, 1254, 1110, 837, 778, 665 cm .
+
+
(
8
KBr plate) 3279 (broad), 2928, 1610, 1580, 1473, 1228, 1111, 1071,
HRMS (ESI-TOF) C H N O (M + H) calcd 394.2090, found
18 28 5 5
−1
+
+
36, 774, 728 cm . HRMS (ESI-TOF) C H N O (M + H) calcd
394.2085.
22
28
5
4
60
426.2141, found 426.2136.
Preparation of 22. Et N·3HF (323 mg, 2.0 mmol) was slowly
3
Preparation of 20. Acetic acid−conc. HCl (1:1, 30 mL) was added
added to 18 (99 mg, 0.2 mmol) in THF (2 mL). The reaction was
stirred at 25 °C overnight, concentrated under vacuum, and purified by
flash chromatography on a silica column. Elution with 10% MeOH in
DCM gave 22 as a light purple foam. The sample was dissolved in
46
to 19 (2.0 g, 10 mmol). The reaction was refluxed at 110 °C for 8 h.
The cooled reaction was quenched by saturated NaHCO solution and
3
extracted with DCM (30 mL × 3). The organic phase was dried over
Na SO . The organic phase was concentrated under vacuum to give 20
MeOH, Na −EDTA was added to the solution, and the reaction was
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4
2
1
as an orange oil (1.75 g, >99%). H NMR (300 MHz, CDCl ) δ 3.12
stirred at 50 °C until the purple color faded. The mixture was cooled
3
(
hept, J = 6.7 Hz, 1H), 1.14 (s, 9H), 1.03 (d, J = 6.7 Hz, 6H).
to room temperature and filtered to remove Na −EDTA. The organic
2
1
3
C NMR (75 MHz, CDCl ) δ 220.1, 44.6, 33.8, 26.0, 20.1. IR (KBr
phase was then concentrated under vacuum give a white foam
3
−1
1
plate) 2973, 2936, 2874, 1732 cm .
(37.5 mg, 70%). H NMR (400 MHz, MeOH-d ) δ 8.36 (s, 1H), 8.20
4
Preparation of 21. Br (176 mg, 1.1 mmol) was slowly added to 20
(s, 1H), 6.44 (dd, J = 7.9, 6.0 Hz, 1H), 4.58 (dt, J = 5.6, 2.7 Hz, 1H),
4.07 (dd, J = 5.8, 3.1 Hz, 1H), 3.84 (dd, J = 12.3, 3.0 Hz, 1H), 3.74
(dd, J = 12.3, 3.4 Hz, 1H), 2.80 (ddd, J = 13.6, 7.9, 5.8 Hz, 1H), 2.42
(ddd, J = 13.4, 6.0, 2.8 Hz, 1H). The spectral data match the literature.
Preparation of Bis-silylated 23. NaH (60% in mineral oil, 20 mg,
0.5 mmol) was slowly added to 18 (241 mg, 0.5 mmol) in THF
(3 mL). The reaction was stirred at 0 °C for 30 min, at which time
2-bromopropane (68 mg, 0.55 mmol) was added at 0 °C. The reaction
was stirred at room temperature for 2 h. The reaction was
concentrated under vacuum and purified by flash chromatography
on a silica column. Elution with 50% EtOAc in hexane gave bis-
silylated 23 as a red oil (70 mg, 26%). 1H NMR (400 MHz,
2
(
128 mg, 1 mmol) in HOAc (2 mL). The reaction was heated at 70 °C
for 5 h, poured into water, and extracted with EtOAc (5 mL × 3). The
organic phase was passed through a silica plug and then concentrated
1
under vacuum to yield 21 as a yellow oil (200 mg, 97%). H NMR
13
(
400 MHz, CDCl ) δ 1.91 (s, 6H), 1.36 (s, 9H). C NMR (75 MHz,
3
CDCl ) δ 209.2, 62.3, 45.5, 31.9, 29.3. IR (KBr plate) 2981, 2876,
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1
733, 1699, 1263, 1194, 1145 cm .
Preparation of 18. TEA (1.01 g, 10 mmol) was added to
hydroxylamine hydrochloride (345 mg, 5 mmol) in THF (10 mL).
After stirring at room temperature for 30 min, 17 (270 mg, 0.5 mmol)
was added, and the reaction was refluxed at 65 °C overnight. The
reaction was concentrated under vacuum and purified by flash
chromatography on a silica column. Elution with 5% MeOH and 1%
MeOH-d ) δ 8.03 (s, 1H), 7.69 (s, 1H), 6.31 (s, 1H), 5.50 (d, J = 10.6
4
Hz, 1H), 4.76−4.59 (m, 1H), 4.27 (hept, J = 6.3 Hz, 1H), 3.95 (dd, J =
8.0, 3.7 Hz, 1H), 3.85 (dd, J = 11.2, 4.6 Hz, 1H), 3.76 (dd, J = 11.2,
3.7 Hz, 1H), 2.80−2.67 (m, 1H), 2.40 (ddd, J = 13.1, 6.2, 4.2 Hz, 1H),
1.29 (d, J = 6.2 Hz, 6H), 0.93 (s, 9H), 0.89 (s, 9H), 0.14 (s, 6H), 0.07
Et N in DCM gave 18 as a light purple foam. The sample was
3
dissolved in MeOH, and Na −EDTA was added to the solution
2
followed by stirring at 50 °C until the purple color faded. The mixture
was cooled to room temperature and filtered to remove Na −EDTA.
(s, 3H), 0.05 (s, 3H). 13C NMR (101 MHz, CDCl ) δ 156.1, 152.9,
2
3
The organic phase was then concentrated under vacuum give a white
149.8, 142.4, 140.7, 140.1, 139.6, 136.0, 120.1, 118.8, 87.9, 84.4, 83.9,
78.0, 75.1, 71.8, 62.8, 41.5, 41.2, 26.0, 25.8, 21.8, 20.6, 18.4, 18.0, −4.6,
−4.8, −5.4, −5.5. IR (KBr plate) 2975, 2920, 1670, 1581, 1412, 1223,
1
foam (143 mg, 58%). H NMR (300 MHz, MeOH-d ) δ 8.20 (s, 1H),
4
8
3
.05 (s, 1H), 6.37 (t, J = 6.4 Hz, 1H), 4.69 (dt, J = 5.6, 4.0 Hz, 1H),
.97 (dd, J = 7.8, 3.6 Hz, 1H), 3.86 (dd, J = 11.2, 4.5 Hz, 1H), 3.76
889, 748, 659 cm . HRMS (ESI-TOF) C H N O Si (M + H)+
−
1
+
25
48
5
4
2
(
dd, J = 11.2, 3.6 Hz, 1H), 2.75 (dt, J = 12.5, 6.1 Hz, 1H), 2.43 (ddd,
J = 13.1, 6.2, 4.2 Hz, 1H), 0.93 (s, 9H), 0.87 (s, 9H), 0.17−0.00
m, 12H). 13C NMR (75 MHz, MeOH-d ) δ 149.7, 147.2, 145.9,
40.3, 139.5, 119.8, 89.2, 85.7, 73.4, 64.0, 41.6, 26.6, 26.5, 19.3, 19.0,
.7, −4.2, −4.3, −5.1. IR (KBr plate) 3408 (broad), 2954, 2929, 2896,
calcd 538.3245, found 538.3240.
Preparation of 23. Et N•3HF (122 mg, 0.76 mmol) was slowly
3
(
1
9
added to bis-silylated 23 (40.5 mg, 0.076 mmol) in THF (1 mL).
The reaction was stirred at 25 °C overnight. The reaction was concen-
trated under vacuum and purified by flash chromatography on a silica
4
H
J. Org. Chem. XXXX, XXX, XXX−XXX