L
E.-K. Jung et al.
Feature
Synthesis
(R)-{2-[4-Bromo-2-methoxy-6-(methoxymethoxy)phenoxy]-3-
[(4-methoxybenzyl)oxy]propoxy}triisopropylsilane (33)
HRMS (ESI+): m/z (M + Na+) calcd for C29H4581BrO7SiNa: 637.1995;
found: 637.1992; m/z (M + Na+) calcd for C29H4579BrO7SiNa: 635.2010;
found: 635.2008.
To a solution of alcohol 6 (0.59 g, 1.60 mmol) in toluene (25 mL) un-
der an atmosphere of N2 was added PPh3 (0.56 g, 2.13 mmol) and the
resultant solution was stirred for 10 min. A solution of phenol 22
(0.28 g, 1.06 mmol) in toluene (12 mL) was then added dropwise and
the mixture was stirred at 0 °C for 20 min. DIAD (0.42 mL, 1.06 mmol)
was added and the solution was allowed to warm to r.t. and stirred for
3 days. Following this, the solvent was removed in vacuo. The crude
product was purified by flash chromatography (19:1 n-hexanes–
EtOAc) to give the title compound 33 (0.47 g, 73%) as a yellow oil;
Rf = 0.64 (4:1 hexanes–EtOAc); [α]D20 +0.40 (c 0.25, CHCl3).
(S)-2-[4-Bromo-2-methoxy-6-(methoxymethoxy)phenoxy]-3-[(4-
methoxybenzyl)oxy]propan-1-ol (35)
To a stirred solution of the silyl ether 33 (0.22 g, 0.35 mmol) in THF
(30 mL) at 0 °C was added 1 M TBAF in THF (1.41 mL, 1.41 mmol)
dropwise and the mixture stirred for 18 h. Sat. aq NaHCO3 (30 mL)
was added and the organic layer separated. The aqueous layer was ex-
tracted with EtOAc (3 × 30 mL). The combined organic extracts were
washed with brine (25 mL), dried (MgSO4) and the solvent was re-
moved in vacuo. The crude product was purified by flash chromatog-
raphy (2:1 hexanes–EtOAc) to give the title compound 35 (0.146 g,
IR (film): 2942, 2865, 1742, 1613, 1588, 1514, 1490, 1421, 1393,
1301, 1230, 1156, 1112, 1072, 1007, 911, 882, 815, 731 cm–1
.
20
94%) as a yellow oil; Rf = 0.37 (2:1 hexanes–EtOAc); [α]D –13.84 (c
1H NMR (400 MHz, CDCl3/TMS): δ = 1.03 {18 H, d, J = 4.8 Hz,
Si[CH(CH3)2]3}, 1.05–1.08 {3 H, m, Si[CH(CH3)2]3}, 3.45 (3 H, s,
OCH2OCH3), 3.70 (1 H, dd, J = 10.4, 5.0 Hz, 3-Ha), 3.77 (3 H, s, 2′-OCH3),
3.78 (3 H, s, 4′′-OCH3), 3.79 (1 H, dd, J = 10.4, 4.0 Hz, 3-Hb), 3.94 (1 H,
dd, J = 10.4, 4.8 Hz, 1-Ha), 3.97 (1 H, dd, J = 10.4, 4.2 Hz, 1-Hb), 4.25–
4.28 (1 H, m, 2-H), 4.45 (1 H, d, J = 11.6 Hz, OCHaHbAr), 4.49 (1 H, d, J =
11.6 Hz, OCHaHbAr), 5.10 (1 H, d, J = 6.8 Hz, OCHaHbCH3), 5.12 (1 H, d,
J = 6.8 Hz, OCHaHbCH3), 6.73 (1 H, d, J = 2.0 Hz, 3′-H), 6.84 (2 H, d, J =
8.4 Hz, 3′′-H), 6.94 (1 H, d, J = 2.0 Hz, 5′-H), 7.19 (1 H, d, J = 8.4 Hz, 2′′-
H).
0.22, CHCl3).
IR (film): 3513, 2921, 2853, 1738, 1611, 1587, 1512, 1489, 1421,
1393, 1224, 1155, 1111, 1069, 1033, 998, 816, 783 cm–1
.
1H NMR (400 MHz, CDCl3/TMS): δ = 3.14 (1 H, t, J = 6.8 Hz, OH), 3.46
(3 H, s, OCH2OCH3), 3.74 (2 H, dd, J = 6.2, 3.6 Hz, 1-CH2), 3.78 (1 H, dd,
J = 10.4, 6.4 Hz, 3-Ha), 3.80 (3 H, s, 4′′-OCH3), 3.81 (3 H, s, 2′-OCH3),
3.83 (1 H, dd, J = 10.4, 5.2 Hz, 3-Hb), 4.15–4.21 (1 H, m, 2-H), 4.48 (1 H,
d, J = 11.6 Hz, OCHaHbAr), 4.53 (1 H, d, J = 11.6 Hz, OCHaHbAr), 5.13 (1
H, d, J = 6.4 Hz, OCHaHbCH3), 5.15 (1 H, d, J = 6.4 Hz, OCHaHbCH3), 6.76
(1 H, d, J = 2.0 Hz, 3′-H), 6.87 (2 H, d, J = 8.4 Hz, 3′′-H), 6.96 (1 H, d, J =
2.0 Hz, 5′-H), 7.24 (1 H, d, J = 8.4 Hz, 2′′-H).
13C NMR (100 MHz, CDCl3): δ = 55.3 (4′′-OCH3), 56.3 (2′-OCH3), 56.5
(OCH2OCH3), 62.2 (C-1), 69.1 (C-3), 73.1 (OCH2Ar), 82.2 (C-2), 95.6
(OCH2OCH3), 110.1 (C-3′), 112.9 (C-5′), 113.8 (C-3′′), 116.5 (C-4′),
129.3 (C-2′′), 130.4 (C-1′′), 135.9 (C-1′), 151.6 (C-6′), 153.9 (C-2′).
13C NMR (100 MHz, CDCl3):
δ = 11.9 {Si[CH(CH3)2]3}, 18.0
{Si[CH(CH3)2]3}, 55.2 (2′-OCH3), 56.1 (4′′-OCH3), 56.3 (OCH2OCH3),
62.5 (C-1), 69.5 (C-3), 72.9 (OCH2Ar), 82.1 (C-2), 95.8 (OCH2OCH3),
110.1 (C-3′), 113.3 (C-5′), 113.6 (C-3′′), 115.7 (C-4′), 129.1 (C-2′′),
130.6 (C-1′′), 136.8 (C-1′), 151.7 (C-6′), 154.2 (C-2′), 159.4 (C-4′′).
HRMS (ESI+): m/z (M + Na+) calcd for C29H4581BrO7SiNa: 637.1995;
found: 637.1978; m/z (M + Na+) calcd for C29H4579BrO7SiNa: 635.2010;
found: 635.1993.
HRMS (ESI+): m/z (M + Na+) calcd for C20H2581BrO7Na: 481.0658;
found: 481.0659; m/z (M + Na+) calcd for C20H2579BrO7Na: 479.0676;
found: 479.0675.
(R)-{2-[5-Bromo-3-methoxy-2-(methoxymethoxy)phenoxy]-3-
[(4-methoxybenzyl)oxy]propoxy}triisopropylsilane (34)
(R)-2-[4-Bromo-2-methoxy-6-(methoxymethoxy)phenoxy]-3-[(4-
To a solution of alcohol 6 (1.12 g, 3.02 mmol) in toluene (40 mL) un-
der an atmosphere of N2 was added PPh3 (1.06 g, 4.03 mmol) and the
resultant solution was stirred for 10 min. A solution of phenol 12
(0.53 g, 2.01 mmol) in toluene (20 mL) was then added dropwise and
the mixture was stirred at 0 °C for 20 min. DIAD (0.79 mL, 4.03 mmol)
was added and the solution was allowed to warm to r.t. and stirred for
3 days. Following this, the solvent was removed in vacuo. The crude
product was purified by flash chromatography (19:1 hexanes–EtOAc)
to give the title compound 34 (0.81 g, 71%) as a yellow oil; Rf = 0.55
(4:1 hexanes–EtOAc); [α]D20 +0.61 (c 0.83, CHCl3).
methoxybenzyl)oxy]propanal (36)
To a stirred solution of alcohol 35 (0.073 g, 0.16 mmol) in CH2Cl2 (10
mL) was added DMP (0.10 g, 0.24 mmol) and the reaction mixture
was left open to atmosphere and stirred at r.t. for 4 h. Sat. aq Na2S2O5
(10 mL) was added followed by sat. aq NaHCO3 (10 mL) and the mix-
ture shaken until no further gas evolved. The layers were separated
and the aqueous layer was extracted with CH2Cl2 (3 × 10 mL). The
combined organic layers were washed with brine (10 mL), dried
(MgSO4) and the solvent removed in vacuo. The crude product was
purified by flash chromatography (19:1 hexanes–EtOAc) to yield the
title compound 36 (0.033 g, 48%) as a pale yellow oil; Rf = 0.72 (2:1
hexanes–EtOAc); [α]D20 +9.82 (c 0.11, CHCl3).
IR (film): 2923, 2865, 1727, 1587, 1513, 1490, 1416, 1247, 1157,
1107, 1037, 1013, 881, 793, 682 cm–1
.
1H NMR (400 MHz, CDCl3/TMS): δ = 1.04 {18 H, d, J = 5.6 Hz,
Si[CH(CH3)2]3}, 1.05–1.07 {3 H, m, Si[CH(CH3)2]3}, 3.54 (3 H, s,
OCH2OCH3), 3.66 (1 H, dd, J = 10.4, 5.0 Hz, 3-Ha), 3.74 (1 H, dd, J = 10.4,
4.4 Hz, 3-Hb), 3.80 (3 H, s, 4′′-OCH3), 3.82 (3 H, s, 3′-OCH3), 3.89 (2 H,
d, J = 5.4 Hz, 1-CH2), 4.38–4.42 (1 H, m, 2-H), 4.47 (2 H, s, OCH2Ar),
5.06 (1 H, d, J = 6.8 Hz, OCHaHbCH3), 5.08 (1 H, d, J = 6.8 Hz, OCHaH-
bCH3), 6.69 (1 H, d, J = 2.2 Hz, 4′-H), 6.86 (2 H, d, J = 8.8 Hz, 3′′-H), 6.88
(1 H, d, J = 2.2 Hz, 6′-H), 7.23 (1 H, d, J = 8.8 Hz, 2′′-H).
IR (film): 2960, 2921, 2852, 1712, 1597, 1514, 1496, 1419, 1361,
1258, 1220, 1151, 1068, 1016, 952, 697 cm–1
.
1H NMR (400 MHz, CDCl3/TMS): δ = 3.44 (3 H, s, OCH2OCH3), 3.79 (3
H, s, 2′-OCH3), 3.80 (3 H, s, 4′′-OCH3), 3.84 (1 H, dd, J = 10.4, 5.2 Hz, 3-
Ha), 3.88 (1 H, dd, J = 10.4, 6.4 Hz, 3-Hb), 4.32 (1 H, td, J = 8.2, 2.0 Hz, 2-
H), 4.48 (1 H, d, J = 11.6 Hz, OCHaHbAr), 4.53 (1 H, d, J = 11.6 Hz,
OCHaHbAr), 5.12 (2 H, s, OCH2CH3), 6.74 (1 H, d, J = 2.0 Hz, 3′-H), 6.86
(2 H, d, J = 8.6 Hz, 3′′-H), 6.96 (1 H, d, J = 2.0 Hz, 5′-H), 7.21 (1 H, d, J =
8.6 Hz, 2′′-H), 9.94 (1 H, d, J = 2.0 Hz, 1-H).
13C NMR (100 MHz, CDCl3):
δ = 11.9 {Si(CH[CH3)2]3}, 18.0
13C NMR (100 MHz, CDCl3): δ = 55.2 (4′′-OCH3), 56.1 (2′-OCH3), 56.4
(OCH2OCH3), 69.5 (C-3), 73.2 (OCH2Ar), 86.4 (C-2), 95.4 (OCH2OCH3),
109.9 (C-3′), 112.7 (C-5′), 113.7 (C-3′′), 116.7 (C-4′), 129.2 (C-2′′),
129.7 (C-1′′), 136.5 (C-1′), 150.9 (C-6′), 153.3 (C-2′), 159.2 (C-4′′),
202.2 (C-1).
{Si[CH(CH3)2]3}, 55.2 (4′′-OCH3), 56.2 (3′-OCH3), 57.3 (OCH2OCH3),
62.6 (C-1), 68.9 (C-3), 73.2 (OCH2Ar), 79.9 (C-2), 98.3 (OCH2OCH3),
109.3 (C-4′), 112.7 (C-6′), 113.8 (C-3′′), 116.2 (C-5′), 129.3 (C-2′′),
130.2 (C-1′′), 135.3 (C-2′), 152.6 (C-1′), 154.2 (C-3′), 159.4 (C-4′′).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–P