The Journal of Organic Chemistry
10.2, 3.9 Hz, 1H), 3.81 (s, 3H), 3.78 (dd, J = 10.1, 3.9 Hz,
Page 8 of 11
MHz, CDCl3): C 159.7, 155.9, 152.0, 129.8, 129.6, 128.9,
126.4, 125.1, 123.3, 120.1, 114.1, 111.7, 110.8, 78.2, 75.8,
73.0, 69.6, 62.9, 55.3, 28.1, 26.3; IR νmax/cm-1 2957, 2924,
2853, 1637, 1080, 1034, 923.
1H), 3.39 (s, 3H), 3.22 (br s, 2H); 13C{1H}-NMR (150 MHz,
CDCl3): C 159.5, 156.0, 152.4, 130.2, 129.6, 126.4, 125.2,
123.3, 120.1, 116.0, 113.9, 111.7, 78.1, 71.7, 68.3, 65.9, 62.5,
57.2, 55.3; IR νmax/cm-1 3998, 2955, 2917, 2849, 1576, 1382,
1222, 1033, 751.
1
2
3
4
5
6
7
8
Homobenzyl ether 12 (27 mg, 16%); Rf = 0.2 (30% EtOAc in
hexane); [α]D22-8.2 (c 0.9, CHCl3); HRMS (ES) calc.
(2S,3S,4S)-2-Hydroxy-3-methoxy-4-((4-methoxybenzyl)oxy)-3,4-
1
for C23H28NO6 (M + NH4)+ 414.1917 found 414.1928; H-
dihydrodibenzo[b,d]furan-1(2H)-one (15). TEMPO (1 mg) and
OxoneTM (28 mg, 0.09 mmol) were sequentially added to a stirred
solution of cis-diol 14 (15 mg, 0.041 mmol) and
tetrabutylammonium bromide (2 mg) in dry CH2Cl2 (4 mL). After
stirring the reaction mixture, overnight at room temperature, it was
concentrated under reduced pressure, and the residue purified by
flash column chromatography (50% EtOAc in hexane) to afford
NMR (600 MHz, CDCl3): H 7.69 (d, J = 7.5 Hz, 1H), 7.52
(d, J = 8.3 Hz, 1H), 7.35 (dt, J = 7.3, 1.2 Hz, 1H), 7.32 (d, J
= 8.6 Hz, 2H), 7.29 (dt, J = 7.5, 1.0 Hz, 1H), 6.89 (d, J = 8.6
Hz, 2H), 5.42 (d, J = 5.7 Hz, 1H), 4.84 (d, J = 11.2 Hz, 1H),
4.74 (d, J = 4.1 Hz, 1H), 4.71 (d, J = 11.2 Hz, 1H), 4.57 (dd,
J = 7.7, 5.8 Hz, 1H), 4.19 (td, J = 7.5, 4.0 Hz, 1H), 3.81 (s,
3H), 2.64 (d, J = 7.5 Hz, 1H), 1.51 (s, 3H), 1.43 (s, 3H);
13C{1H}-NMR (150 MHz, CDCl3): C 159.6, 155.9, 152.2,
129.8, 129.4, 126.5, 125.3, 123.4, 120.3, 114.0, 113.6, 111.7,
110.8, 77.6, 72.3, 71.5, 70.3, 69.5, 55.3, 28.2, 26.2; IR
νmax/cm-1 2958, 2925, 2853, 1641, 1080, 1012, 907.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ketone 15 (12.8 mg, 86%), a pale-yellow oil; Rf = 0.3 (50% EtOAc
22
in
hexane);
[α]D
-118.0
(c
1.0,
CHCl3); HRMS (ES) calc. for C21H20O6Na (M + Na)+ 391.1158
found 391.1155; 1H-NMR (600 MHz, CDCl3): H 8.08 (dm, 1H),
7.58 (m, 1H), 7.44 (td, J = 7.3, 1.5 Hz, 1H), 7.42-7.38 (m, 3H),
6.91 (d, J = 8.7 Hz, 2H), 5.04 (d, J = 3.8 Hz, 1H), 4.88 (dd, J =
9.9, 1.0 Hz, 1H), 4.83 (d, J = 11.7 Hz, 1H), 4.80 (d, J = 11.7 Hz,
1H), 3.81 (s, 3H), 3.72 (dd, J = 9.9, 3.7 Hz, 1H), 3.59 (d, J = 1.2
Hz, 1H), 3.54 (3H, s, 3H); 13C{1H}-NMR (150 MHz, CDCl3):
C191.5, 165.9, 159.4, 156.2, 130.1 (2), 129.1, 126.7, 125.3, 122.5
(2), 116.1, 114.0 (2), 111.9, 83.1, 73.6, 72.5, 67.4, 58.2, 55.4; IR
νmax/cm-1 3844, 3681, 2948, 2880, 1652, 1410, 1128, 1044, 852.
A small portion of the minor diastereoisomer 10b was
separated from the acetal mixture 10a/10b by multiple elution
PLC. This sample on similar DIBAL reduction gave
exclusively isomer 12.
(3aR,4S,5S,10cR)-4-Methoxy-5-((4-methoxybenzyl)oxy)-2,2-
dimethyl-3a,4,5,10c-tetrahydrobenzo[b][1,3]dioxolo[4,5-
e]benzofuran (13). To a solution of alcohol 11 (16 mg, 0.040
mmol) in dry THF (4 mL) was added sodium hydride (5 mg),
under an argon atmosphere, followed by the addition of
methyl iodide (12 µL). The reaction mixture was stirred (4 h)
at room temperature, the solvent removed under reduced
pressure, and the crude product purified by flash column
chromatography (10% EtOAc-hexane), to afford methyl
ether 13 (14.9 mg, 90%), colorless oil; Rf = 0.2 (20% EtOAc
in hexane); [α]D22 -95.6 (c 0.5, CHCl3); HRMS (ES) calc. for
(2S,3R,4S)-2,3-Dimethoxy-4-((4-methoxybenzyl)oxy)-3,4-
dihydrodibenzo[b,d]furan-1(2H)-one (16).
Following the
procedure described for the synthesis of methyl ether 9, a mixture
of ketone 15 (9.2 mg, 0.025 mmol), Ag2O (8.0 mg) and MeI (10
µL) in dry THF (2 mL) was heated in a sealed tube under argon
atmosphere. The crude product obtained was purified by flash
column chromatography (20% EtOAc in hexane) to give
dimethoxy ketone 16 (7.3 mg, 76%), colorless oil; Rf = 0.2 (30%
EtOAc in hexane); [α]D22 -139.0 (c 0.7, CHCl3); HRMS (ES) calc.
for C22H23O6 (M + H)+ 383.1495 found 383.1471; 1H-NMR (600
MHz, CDCl3): H 8.09 (dm, J = 7.7 Hz, 1H), 7.55 (m, 1H), 7.43-
7.35 (m, 4H), 6.92 (d, J = 8.7 Hz, 2H), 5.05 (d, J = 3.8 Hz, 1H),
4.88 (d, J = 11.8 Hz, 1H), 4.80 (d, J = 11.8 Hz, 1H), 4.31 (d, J =
8.5 Hz, 1H), 3.98 (dd, J = 8.4, 3.7 Hz, 1H), 3.82 (s, 3H), 3.70 (s,
3H), 3.52 (s, 3H); 13C{1H}-NMR (150 MHz, CDCl3): C 190.9,
165.3, 159.6, 155.9, 130.0, 129.3, 126.2, 125.0, 123.1, 122.5,
116.4, 114.0, 111.7, 82.5, 81.9, 72.6, 68.7, 60.5, 59.0, 55.4; IR ν
max/cm-1 2947, 2880, 1739, 1684, 1484, 1281, 1041.
1
C24H30NO6 (M + NH4)+ 428.2073 found 428.2052; H-NMR
(600 MHz, CDCl3): H 7.68 (d, J = 7.7 Hz, 1H), 7.51 (d, J =
8.2 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.34 (dt, J = 7.3, 1.3
Hz, 8H), 7.29 (dt, J = 7.61.0 Hz, 9H), 6.89 (d, J = 8.6 Hz,
1H), 5.43 (d, J = 6.2 Hz, 1H), 4.81 (d, J = 3.6 Hz, 1H), 4.75
(d, J = 11.7 Hz, 1H), 4.74 (dd, J = 8.5, 6.2 Hz, 1H), 4.68 (d,
J = 11.7 Hz, 1H), 3.80 (s, 3H), 3.67 (dd, J = 8.5, 3.6 Hz, 1H),
3.48 (s, 3H), 1.52 (s, 3H), 1.49 (s, 3H); 13C{1H}-NMR (150
MHz, CDCl3): C 159.4, 155.9, 152.9, 129.9, 129.8, 126.4,
125.2, 123.4, 120.4, 113.8, 113.4, 111.7, 110.7, 81.6, 76.1,
71.7, 69.4, 66.9, 58.1, 55.3, 28.2, 25.8; IR νmax/cm-1 2956,
2924, 2854, 1514, 1249, 1109, 874.
(2S,3R,4S)-4-Hydroxy-2,3-dimethoxy-3,4-
dihydrodibenzo[b,d]furan-1(2H)-one [(_)-Ribisin B]. 1, 7
Following the procedure described for the last step in the literature
synthesis of (_)-ribisin A, a solution of dimethoxy ketone 16 (7.6
mg, 0.020 mmol) in CH2Cl2 and H2O (4:1, 2 mL) was reacted with
DDQ (5 mg). Purification of the crude product by flash column
chromatography (25% EtOAc in hexane) furnished (_)-ribisin B
(4.0 mg, 77%), as a colorless oil; Rf = 0.2 (30% EtOAc in hexane);
[α]D22 -25.8 (c 0.4, CHCl3); HRMS (ES) calc. for C14H15O5 (M +
H)+ 263.0919 found 263.0912; 1H-NMR (600 MHz, CDCl3): H
8.08 (dm, J = 7.6 Hz, 1H), 7.56 (dm, J = 7.7 Hz, 1H), 7.41-7.35
(m, 2H), 5.30 (dd, J = 7.1, 4.2 Hz, 1H), 4.15 (d, J = 6.7 Hz, 1H),
4.01 (dd, J = 6.7, 4.2 Hz, 1H), 3.62 (s, 3H), 3.61 (s, 3H), 3.05 (d,
J = 7.1 Hz, 1H); 13C{1H}-NMR (150 MHz, CDCl3): C 190.2,
165.2, 155.8, 126.1, 124.9, 123.1, 122.3, 115.3, 111.8, 81.9, 81.7,
63.8, 59.8, 59.5.
(1R,2R,3S,4S)-3-Methoxy-4-((4-methoxybenzyl)oxy)-
1,2,3,4-tetrahydrodibenzo[b,d]furan-1,2-diol
(14).
A
solution of methyl ether 13 (8.0 mg, 0.020 mmol) in THF-
H2O (9:1, 2 mL) was treated with TFA (10 µL). The reaction
mixture was stirred (50°C) overnight, concentrated under
reduced pressure, and the product purified by flash column
chromatography (60% EtOAc in hexane), to yield cis-diol 14
(7.0 mg, 97%), colorless oil; Rf = 0.2 (60% EtOAc-hexane);
22
[α]D
-139.0 (c 0.7, CHCl3); HRMS (ES) calc. for
1
C21H22O6Na (M + Na)+ 393.1314 found 393.1302; H-NMR
(600 MHz, CDCl3): H 7.68 (d, J = 7.7 Hz, 1H), 7.51 (d, J =
8.2 Hz, 1H), 7.40 (d, J = 8.6 Hz, 2H), 7.34 (dt, J = 7.3, 1.3
Hz, 1H), 7.28 (dt, J = 7.6, 1.0 Hz, 1H), 6.90 (d, J = 8.6 Hz,
2H), 5.16 (d, J = 4.2 Hz, 1H), 4.84 (d, J = 3.9 Hz, 1H), 4.80
(d, J = 11.7 Hz, 1H), 4.74 (d, J = 11.7 Hz, 1H), 4.37 (dd, J =
8
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