European Journal of Organic Chemistry
10.1002/ejoc.201700566
FULL PAPER
solution of 6 (38.72 g, 33.63 mmol) in THF (50 mL). The reaction was
58.4, 59.0, 66.7, 69.3, 69.6, 69.9, 70.2, 70.4, 85.1, 86.4, 122.7 (q, J =
stirred at room temperature overnight. The reaction mixture was
286 Hz), 123.6, 125.8, 126.7, 128.0, 129.6, 131.8, 131.9, 144.8; 19F NMR
quenched at 0 °C with 30% NaOH/H
O (mL) = 1 : 2 : 3). The combined organic layers were dried over
anhydrous Na SO , filtered and concentrated under reduced pressure.
The resulting residue was purified by column chromatography
2
O (LiAlH
4
(g): 30% NaOH (mL):
3 38 6
(376 MHz, CDCl ) δ -78.64; HRMS (ESI) calcd for C42H F12NaO
S+
+
H
2
921.2090 ((M+Na) ), found 921.2098.
Synthesis of 14: Under an argon atmosphere, a mixture of bromide 8
(27.79 g, 23.43 mmol), alcohol 13 (7.80 g, 8.68 mmol), dry K CO (3.60 g,
2
4
2
3
(
(
MeOH/DCM = 1/50) to give 7 as clear oil (37.02 g, 98% yield). 1H NMR
400 MHz, CDCl ) δ 3.38 (s, 9H), 3.51-3.89 (m, 81H), 4.09-4.21 (m, 6H),
.57 (d, J = 8.0 Hz, 2H), 6.63 (s, 2H); 13C NMR (100 MHz, CDCl
) δ 58.8,
26.03 mmol) and 18-crown-6 (0.46 g, 1.74 mmol) in anhydrous acetone
(100 mL) was refluxed for 36 h. Then, the mixture was allowed to cool to
rt. The reaction was quenched with water (200 mL) and the resulting
mixture was extracted with EtOAc (200 mL, five times). The organic
3
4
6
3
4.3, 68.5, 69.6, 70.3, 70.4, 70.6, 71.7, 72.1, 105.9, 137.0, 137.3, 152.3;
+
MS (MALDI-TOF) m/z 1145.6 ((M+Na) ), found 1145.6.
4
layers were combined, dried over anhydrous MgSO , filtered and
Synthesis of 8: Under an argon atmosphere, to a stirring solution of
alcohol 7 (30.60 g, 27.24 mmol) in dry DCM (150 mL) was slowly added
concentrated under vacuum. The residue was purified by column
chromatography (MeOH/DCM = 1/25) to give 14 as clear oil (25.10 g,
1
PBr
3
(7.76 mL, 81.72 mmol) at 0 °C and the resulting mixture was stirred
93% yield). H NMR (400 MHz, CDCl
3
) δ 2.44 (t, J = 8.0 Hz, 2H), 3.39 (s,
at rt for 5 h. The reaction mixture was quenched with EtOH, extracted
with EtOAc (150 mL, 3 times). The combined organic layers were dried
18H), 3.52-3.60 (m, 15H), 3.61-3.77 (m, 143H), 3.77-3.88 (m, 13H), 4.10
(t, J = 8.0 Hz, 8H), 4.15 (t, J = 4.0 Hz, 4H), 4.43 (s, 2H), 4.49 (s, 4H),
6.57 (s, 4H), 7.18-7.24 (m, 3H), 7.25-7.28 (m, 3H), 7.29-7.32 (m, 2H),
over anhydrous MgSO
dryness. The residue was purified by column chromatography
MeOH/DCM = 1/50) to give bromide 8 as clear oil (28.43 g, 86% yield).
1H NMR (400 MHz, CDCl
) δ 3.38 (s, 9H), 3.52-3.89 (m, 80H), 4.10-4.19
m, 6H), 4.43 (d, J = 4.0 Hz, 2H), 6.64 (d, J = 8.0 Hz, 2H); 13C NMR (100
4
, filtered and evaporated under vacuum to
7.37-7.46 (m, 6H), 7.82 (s, 2H), 7.90 (s, 1H); 13C NMR (100 MHz, CDCl
3
)
(
δ 18.3, 31.5, 57.8, 58.9, 66.5, 68.5, 68.8, 69.5, 70.0, 70.3, 70.4, 70.5,
70.6, 71.8, 72.2, 83.9, 88.2, 107.1, 122.0 (q, J = 288 Hz), 124.9, 126.6,
127.8, 129.4, 129.5, 130.3, 133.2, 138.3, 144.7, 152.7; 19F NMR (376
3
(
MHz, CDCl
3
) δ 34.0, 58.8, 68.7, 69.5, 70.3, 70.4, 70.6, 71.7, 72.1, 108.5,
99BrO242+ 593.2850
MHz, CDCl
3
) δ -73.65; HRMS (MALDI-TOF) m/z 3130.4673 ((M+Na)+),
132.8, 138.3, 152.4; HRMS (ESI) calcd for C52
H
found 3130.3416.
(
(M+2H)2+), found 593.2827.
Synthesis of 1c: A solution of I
2
(2.05 g, 8.07 mmol) in CH Cl
2
2
(20 mL)
Synthesis of 10: 10 was prepared by following the same procedure for 5
from alcohol 4 as clear oil (30.02 g, 96% yield). 1H NMR (400 MHz,
was added to a solution of 14 (25.10 g, 8.07 mmol) in CH
2
Cl (50 mL) in
2
portion over 30 min. The mixture was stirred at rt for 4 h and then
quenched with 10% aqueous sodium thiosulfate (20 mL). The mixture
CDCl
3
) δ 2.39-2.49 (m, 4H), 3.59 (s, 4H), 3.62-3.72 (m, 10H), 4.16 (t, J =
.0 Hz, 2H), 4.20 (d, J = 2.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.80 (d, J =
.0 Hz, 2H).
4
8
2 4
was washed with brine, dried by Na SO , and concentrated under
vacuum to provide pale-yellow oil. Purification by column
Synthesis of 11: A mixture of 10 (30.02 g, 77.68 mmol), TrtSH (27.91 g,
00.98 mmol) and K CO (21.47 g, 155.36 mmol) in H O/EtOH (1:1, 300
chromatography (MeOH/DCM = 1/25) to give the desired product 1c
1
1
2
3
2
(18.99 g, 82% yield) as pale-yellow oil. H NMR (400 MHz, CDCl
3
) δ 2.87
mL) was refluxed for 18 h. The resulting mixture was extracted with
EtOAc (250 mL, three times). The combined organic layers were
concentrated under vacuum and purified by column chromatography
(t, J = 4.0 Hz, 4H), 3.37 (s, 36H), 3.50-3.57 (m, 25H), 3.60-3.74 (m,
297H), 3.82 (t, J = 4.0 Hz, 18H), 4.08 (t, J = 4.0 Hz, 15H), 4.14 (t, J = 4.0
Hz, 9H), 4.44 (s, 4H), 4.48 (s, 8H), 6.57 (s, 8H), 7.81 (s, 4H), 7.88 (s,
(EtOAc/Petroleum ether = 1/5) to give 11 as pale-yellow oil (33.54 g, 88%
2H); 13C NMR (100 MHz, CDCl
3
) δ 38.3, 53.6, 58.9, 68.4, 68.8, 69.4,
1
yield). H NMR (400 MHz, CDCl
3
) δ 2.40-2.46 (m, 3H), 3.29 (t, J = 8.0 Hz,
69.4, 69.6, 70.0, 70.2, 70.26, 70.29, 70.38, 70.44, 70.5, 71.7, 72.1, 83.8,
2
H), 3.42-3.46 (m, 2H), 3.54-3.58 (m, 2H), 3.61-3.69 (m, 9H), 4.18 (d, J =
.4 Hz, 2H), 7.17-7.27 (m, 6H), 7.28-7.33 (m, 2H), 7.38-7.46 (m, 7H); 13C
) δ 31.8, 58.4, 66.6, 69.1, 69.6, 70.2, 70.4, 70.5,
0.6, 75.0, 79.8, 126.8, 128.0, 129.7, 144.9; HRMS (ESI) calcd for
88.3, 106.9, 122.0 (q, J = 290 Hz), 125.0, 127.4, 129.3, 130.6, 133.2,
2
137.8, 152.5; 19F NMR (376 MHz, CDCl
Synthesis of 1b: Under an argon atmosphere, PEt
2
mmol) was added to a solution of 1c (18.99 g, 3.31 mmol) in THF/H O
3
) δ -73.59.
NMR (100 MHz, CDCl
3
3
(1.02 mL, 6.96
7
+
+
C
30
H
34NaO
4
S 513.2070 ((M+Na) ), found 513.2066.
(9/1, 20 mL). The resulting mixture was stirred at rt. After 1 h, the organic
solvent was removed under reduced pressure. Under an atmosphere of
Ar, a solution of 1a (18.98 g, 6.62 mmol) and NaOH (0.53 g, 13.24 mmol)
Synthesis of 13: Under an argon atmosphere, to a mixture of alcohol
210 (30.54 g, 56.97 mmol), Pd(PPh
Cl (2.00 g, 2.85 mmol) and CuI
N (250 mL) was added a solution of 11
N (25 mL) at rt and the resulting mixture
1
3
)
2
2
(
0.43 g, 2.28 mmol) in dry Et
3
3
in EtOH (50 mL) was stirred for 10 min at 0 °C. CH I (0.82 mL, 13.24
(
33.54 g, 68.36 mmol) in dry Et
3
mmol) was then added dropwise to the mixture over a period of 20 min at
0 °C. The mixture was stirred at ambient temperature overnight. The
solvent was evaporated under reduced pressure, and the residue was
purified by column chromatography (MeOH/DCM = 1/25) to afford the
sulfide 1b as colorless oil (12.80 g, 67% yield). 1H NMR (400 MHz,
was stirred at this temperature overnight. The resulting mixture was
extracted with EtOAc (250 mL, 2 times). The combined organic layers
4
were dried over anhydrous MgSO , filtered, concentrated under vacuum
and purified by column chromatography (EtOAc/Petroleum ether = 1/7) to
give alcohol 13 as clear oil (47.11 g, 92% yield). 1H NMR (400 MHz,
3
CDCl ) δ 2.93 (t, J = 4.0 Hz, 2H), 3.38 (s, 18H), 3.52-3.58 (m, 12H), 3.58-
CDCl
3
) δ 2.43 (t, J = 8.0 Hz, 2H), 3.26 (t, J = 8.0 Hz, 2H), 3.36-3.46 (m,
H), 3.49-3.57 (m, 2H), 3.60-3.70 (m, 6H), 3.71-3.77 (m, 2H), 4.36 (s,
H), 5.65 (s, 2H), 7.16-7.26 (m, 6H), 7.27-7.30 (m, 2H), 7.38-7.7.46 (m,
H), 7.87 (s, 2H), 8.12 (s, 1H); 13C NMR (100 MHz, CDCl
) δ 17.7, 31.4,
3.69 (m, 130H), 3.69-3.81 (m, 23H), 3.83 (t, J = 4.0 Hz, 9H), 4.10 (t, J =
4.0 Hz, 8H), 4.14 (t, J = 4.0 Hz, 4H), 4.39-4.59 (m, 6H), 6.57 (s, 4H),
2
2
7
7.72-7.92 (m, 2H), 8.01 (s, 1H); 13C NMR (100 MHz, CDCl
3
) δ 5.58, 5.63,
3
8.7, 15.8, 19.2, 19.8, 30.6, 33.3, 38.2, 46.3, 58.9, 68.3, 68.5, 68.8, 69.5,
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