The Journal of Organic Chemistry
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mL, 70.5 mmol) in dry THF (70 mL) containing 28.2 mL (28.2
mmol) of 2.5 M nBuLi at −78 °C was stirred for 30 min. Acetate ester
17 (14.8 g, 70.5 mmol) was added dropwise, and the resulting solution
was stirred for 1 h followed by addition of aldehyde 16 (11.5 g, 58.8
mmol). After 3 h of additional stirring at the same temperature, the
mixture was diluted with H2O and extracted with EtOAc. The organic
layer was dried and evaporated in vacuo to give a residue that was
subjected to column chromatography (EtOAc:hexane 1:3) to yield
1H), 4.51 (d, 1H, J = 6.5 Hz), 4.56 (d, 1H, J = 6.5 Hz), 4.87 (d, 1H, J
= 1.5 Hz), 6.63 (d, 1H, J = 8.0 Hz), 6.71 (t, 1H, J = 7.0 Hz), 6.76−6.81
(m, 4H), 7.22−7.27 (m, 3H), 7.68 (d, 2H, J = 8.5 Hz); 13C NMR
(CDCl3) δ 21.5, 55.2, 55.7, 55.8, 68.5, 76.1, 81.6, 94.4, 112.5, 113.6,
119.2, 120.8, 123.1, 127.9, 128.9, 129.6, 133.0, 144.5, 147.1, 150.9,
159.4; HRMS (ES) m/z 525.1561 (M + Na, C26H30O8SNa requires
525.1559).
Acetonide and MOM Protected Tetramer 26EE. To a solution
of MeCN (60 mL) containing 25E (1.15 g, 3.2 mmol) was added NaH
(60% mineral oil) (190 mg, 4.8 mmol) at room temperature. After 1 h
of stirring at 80 °C, 23E (1.6 g, 3.2 mmol) was added, and the solution
was stirred for 24 h at the same temperature. The solution was
concentrated following extraction with CH2Cl2, drying, and concen-
tration in vacuo to afford a residue that was subjected to column
chromatography (EtOAc:hexane 1:1) to yield diastereomeric 26EE
(1.1 g, 48%). 1H NMR (CDCl3) δ 1.49 (s, 3H), 1.62 (s, 3H), 3.31 (s,
3H), 3.68 (s, 3H), 3.72 (s, 6H), 3.77 (s, 3H), 3.97−4.01 (m, 1H),
4.11−4.13 (m, 2H), 4.20−4.23 (m, 1H), 4.29−4.32 (m, 1H), 4.59 (d,
1H, J = 6.5 Hz), 4.66 (d, 1H, J = 6.0 Hz), 4.70−4.73 (m, 1H), 4.86−
4.88 (m, 1H), 5.07 (d, 1H, J = 4 Hz), 6.42−6.45 (m, 1H), 6.63−6.67
(m, 1H), 6.72−6.83 (m, 8H), 6.87−6.90 (m, 1H), 6.96−6.99 (m, 3H),
7.34 (d, 1H, J = 8 Hz); 13C NMR (CDCl3) δ 19.7, 28.5, 55.2, 55.6,
55.7, 55.9, 62.9, 68.0, 74.6, 82.5, 94.6, 99.4, 111.6, 112.2, 112.4, 113.5,
117.6, 118.0, 118.8, 119.8, 120.8, 122.4, 122.7, 129.1, 130.1, 132.3,
147.2, 148.1, 148.3, 148.6, 150.5, 150.9, 159.3; HRMS (ES) m/z
713.2943 (M + Na, C39H46O11Na requires 713.2938).
Tetramer 12EE. To solution of THF (60 mL) containing 26EE
(1.8 g, 2.5 mmol) was added 3 N HCl (3 mL) at room temperature,
and the solution was stirred for 12 h at 50 °C. The solution was
concentrated following extraction with CH2Cl2, drying, and concen-
tration in vacuo to afford a residue that was subjected to column
chromatography (EtOAc:hexane 2:1) to yield diastereomeric 12EE
(0.81 g, 51%). 1H NMR (CDCl3) δ 3.60−3.63 (m, 1H), 3.77 (s, 3H),
3.80 (s, 3H), 3.85 (s, 6H), 4.00−4.02 (m, 1H), 4.10−4.13 (m, 2H),
4.35−4.40 (m, 1H), 4.55−4.58 (m, 1H), 4.93 (d, 1H, J = 3.5 Hz), 5.01
(d, 1H, J = 3.5 Hz), 6.71 (d, 1H, J = 8 Hz), 6.78 (t, 2H, J = 8 Hz),
6.83−6.93 (m, 8H), 7.00−7.05 (m, 2H), 7.32 (d, 2H, J = 7 Hz); 13C
NMR (CDCl3) δ 55.2, 55.9, 60.8, 68.4, 72.7, 73.8, 84.9, 87.4, 109.9,
112.0, 113.7, 113.9, 118.4, 121.1, 121.3, 121.4, 121.6, 123.9, 124.2,
127.6, 128.4, 131.8, 133.4, 146.9, 147.5, 147.6, 148.4, 149.8, 150.9,
151.6, 151.7, 159.0; HRMS (ES) m/z 629.2351 (M + Na,
C34H38O10Na requires 629.2363).
Synthesis of Tetrameric Model Compound 13EE. Tosylate
22E. To a solution of 50 mL of CH2Cl2 containing 11E (1.0 g, 2.7
mmol) was added NEt3 (1.2 mL, 8.2 mmol) at 0 °C. After being
stirred for 1 h, TsCl (1.1 g, 5.8 mmol) was added at 0 °C, and the
solutions was stirred for 12 h at room temperature. The solution was
extracted with CH2Cl2 followed by drying and concentration in vacuo
to afford a residue that was subjected to column chromatography
(EtOAc:hexane 1:2) to yield 22E (0.94 g, 66%). 1H NMR (CDCl3) δ
2.39 (s, 3H), 3.79 (s, 6H), 3.81 (s, 6H), 4.07 (d, 1H, J = 11 Hz), 4.28−
4.32 (m, 1H), 4.35−4.38 (m, 1H), 4.83 (d, 1H, J = 3.5 Hz), 6.51 (s,
2H), 6.89 (d, 2H, J = 8.0 Hz), 6.97 (d, 1H, J = 7 Hz), 7.04 (t, 1H, J =
7.5 Hz), 7.23 (d, 2H, J = 8.5 Hz), 7.64 (d, 2H, J = 8.0 Hz); 13C NMR
(CDCl3) δ 21.6, 55.8, 56.1, 60.8, 68.5, 71.9, 84.4, 103.1, 112.3, 121.1,
121.6, 124.4, 127.9, 129.7, 132.8, 134.0, 137.5, 144.8, 146.5, 151.6,
153.3; HRMS (ES) m/z 541.1510 (M + Na, C26H30O9SNa requires
541.1508).
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erythro 20E (18.2 g, 76%) exclusively. H NMR (CDCl3) δ 1.14 (t,
3H, J = 7 Hz), 3.66 (d, 1H, J = 6 Hz), 3.81 (s, 3H), 3.83 (s, 6H), 3.84
(s, 3H), 4.14 (dd, 2H, J = 7 Hz, J = 14 Hz), 4.71 (d, 1H, J = 5.5 Hz),
5.12 (t, 1H, J = 5.5 Hz), 6.70 (s, 2H), 6.82−6.85 (m, 1H), 6.88−6.90
(m, 2H), 6.99−7.02 (m, 1H); 13C NMR (CDCl3) δ 14.0, 55.8, 56.0,
60.8, 61.3, 74.0, 83.6, 103.9, 112.2, 118.6, 121.0, 123.9, 134.7, 137.6,
147.1, 150.5, 153.0, 169.3; HRMS (ES) m/z 429.1520 (M + Na,
C21H26O8Na requires 429.1525).
1-(4-Methoxyphenyl)-2-(methoxyphenyloxy)-1,3-propan-
diol 9E. To a solution of THF containing 1.0 M LiAlH4 (12.8 mL,
12.8 mmol) was added 18E (4.4 g, 12.8 mmol) at room temperature.
After being stirred for 3 h, 20 mL of H2O and 20 mL of 1 N HCl
solution at 0 °C were added, and the solution was extracted with
CH2Cl2. The extracts were dried and concentrated in vacuo to afford a
residue that was subjected to column chromatography (EtOAc:hexane
1
1:1) to yield 9E (2.1 g, 55%). H NMR (CDCl3) δ 2.84−2.86 (m,
1H), 3.54 (d, 1H, J = 3.5 Hz), 3.60−3.65 (m, 1H), 3.78 (s, 3H), 3.85
(s, 3H), 3.85−3.91 (m, 1H), 4.11−4.14 (m, 1H), 4.96−4.98 (m, 1H),
6.85−6.94 (m, 5H), 7.04 (t, 1H, J = 8 Hz), 7.29 (d, 2H, J = 8.5 Hz);
13C NMR (CDCl3) δ 55.2, 55.8, 60.6, 72.5, 87.4, 112.1, 113.8, 121.0,
121.6, 124.2, 127.2, 131.9, 146.8, 151.6, 159.0; HRMS (ES) m/z
327.1211 (M + Na, C17H20O5Na requires 327.1208).
1-(3,4,5-Trimethoxyphenyl)-2-(methoxyphenyloxy)-1,3-
propandiol 11E. To a solution of THF containing 1.0 M LiAlH4 (7.4
mL, 7.4 mmol) was added 20E (3.0 g, 7.4 mmol) at room
temperature. After being stirred for 3 h, 20 mL of H2O and 20 mL
of 1 N HCl solution at 0 °C were added, and the solutions were
extracted with CH2Cl2. The extracts were dried and concentrated in
vacuo to afford a residue that was subjected to column
1
chromatography (EtOAc:hexane 1:1) to yield 11E (1.6 g, 59%). H
NMR (CDCl3) δ 2.69−2.72 (m, 1H), 3.56 (d, 1H, J = 3 Hz), 3.61−
3.65 (m, 1H), 3.81 (s, 3H), 3.82 (s, 6H), 3.87 (s, 6H), 3.87−3.93 (m,
1H), 4.13−4.15 (m, 1H), 4.93−4.95 (m, 1H), 6.59 (s, 2H), 6.90−6.98
(m, 3H), 7.05−7.08 (m, 1H); 13C NMR (CDCl3) δ 55.9, 56.1, 60.7,
60.8, 72.8, 87.4, 102.9, 112.1, 121.2, 121.6, 124.4, 135.4, 137.3, 146.7,
151.6, 153.3; HRMS (ES) m/z 387.1417 (M + Na, C19H24O7Na
requires 387.1420).
Synthesis of Tetrameric Model Compound 12EE. Tosylate
21E. To a solution of CH2Cl2 containing 9E (1.9 g, 6.2 mmol) was
added NEt3 (1.6 mL, 11.4 mmol) at 0 °C. After being stirred for 1 h,
TsCl (1.3 g, 6.8 mmol) was added at 0 °C, and the solution was stirred
for 12 h at room temperature. The solution was extracted with
CH2Cl2, followed by drying and concentration in vacuo to afford a
residue that was subjected to column chromatography (EtOAc:hexane
1:2) to yield 21E (2.0 g, 70%). 1H NMR (CDCl3) δ 2.39 (s, 3H), 3.77
(s, 3H), 3.81 (s, 3H), 4.07 (d, 1H, J = 10.5 Hz), 4.28−4.32 (m, 1H),
4.32−4.36 (m, 1H), 4.85 (d, 1H, J = 3 Hz), 6.81 (d, 2H, J = 8.5 Hz),
6.88 (d, 2H, J = 8.0 Hz), 6.95 (d, 1H, J = 7.5 Hz), 7.03 (t, 1H, J = 7.5
Hz), 7.18 (d, 2H, J = 8.5 Hz), 7.23 (d, 2H, J = 8.5 Hz), 7.65 (d, 2H, J
= 8.0 Hz); 13C NMR (CDCl3) δ 21.5, 55.2, 55.8, 68.4, 71.6, 84.4,
112.3, 113.8, 114.0, 121.1, 121.5, 124.3, 127.2, 127.9, 129.7, 130.5,
132.8, 144.6, 145.6, 151.5, 159.1; HRMS (ES) m/z 481.1300 (M + Na,
C24H26O7SNa requires 481.1297).
TMS Protected Tosylate 24E. To a solution of THF containing
22E (1.4 g, 2.7 mmol) was added imidazole (0.6 g, 8.1 mmol) at room
temperature. After being stirred for 30 min, TMSCl (0.9 g, 8.1 mmol)
was added at the same temperature, and the solution was stirred for 10
h. The solution was extracted with CH2Cl2 followed by drying and
concentration in vacuo to afford a residue that was subjected to
column chromatography (EtOAc:hexane 1:3) to yield 24E (0.77 g,
MOM Protected Tosylate 23E. To a solution of THF containing
21E (1.0 g, 2.2 mmol) was added iPr2NEt (1.5 mL, 8.7 mmol) at 0 °C.
After being stirred for 30 min, MOMCl (1.0 mL, 13.1 mmol) was
added at 0 °C, and the solution was stirred for 12 h at room
temperature. The solution was extracted with CH2Cl2 followed by
drying and concentration in vacuo to afford a residue that was
subjected to column chromatography (EtOAc:hexane 1:3) to yield
1
48%). H NMR (CDCl3) δ 0.02 (s, 9H), 2.39 (s, 3H), 3.68 (s, 3H),
3.78 (s, 6H), 3.80 (s, 3H), 4.30−4.33 (m, 2H), 4.37−4.40 (m, 1H),
6.53 (d, 1H, J = 8.5 Hz), 6.55 (s, 2H), 6.68 (t, 1H, J = 6.5 Hz), 6.76 (d,
1H, J = 7.0 Hz), 6.87 (t, 1H, J = 7.0 Hz), 7.22 (d, 2H, J = 8.0 Hz), 7.66
(d, 1H, J = 8.5 Hz); 13C NMR (CDCl3) δ 0.0, 21.6, 55.6, 56.1, 60.8,
1
23E (0.69 g, 62%). H NMR (CDCl3) δ 2.40 (s, 3H), 3.30 (s, 3H),
3.68 (s, 3H), 3.77 (s, 3H), 4.32 (d, 1H, J = 7.5 Hz), 4.40−4.46 (m,
9440
dx.doi.org/10.1021/jo401680z | J. Org. Chem. 2013, 78, 9431−9443