Total Synthesis of (R)-Semixanthomegnin
55
Experimental
121.1, 131.5 (C4), 137.7, 152.7, 158.0, 162.3, 164.1. Mass spectrum
•
•
(ESI) m/z 487 ([M + H]+ 37Cl), 485 ([M + H]+ 35Cl).
, ,
General
Methyl (R)-(–)-3-(2ꢀ-tert-Butyldimethylsilyloxy) propyl-6-chloro-1-
methoxy-5,8-dioxonaphthalene-2-carboxylate (22) and Methyl
(R)-(–)-3-(2ꢀ-tert-Butyldimethylsilyloxy) propyl-6,7-dichloro-1-
methoxy-5,8-dioxonaphthalene-2-carboxylate (23)
Melting points were determined on a hot-stage apparatus and are
uncorrected. IR spectra were recorded using a Perkin-Elmer 983 G
spectrophotometer for samples as potassium bromide disks. Electronic
spectra were recorded on a Shimadzu UV-2401PC spectrophotometer
using either ethanol or methanol solutions in a 10 mm quartz cell.
NMR spectra were recorded with JEOL JNM-GX-400 andVarian Unity
400 spectrometers (1H at 400 MHz and 13C at 100 MHz) for solutions
in CDCl3 unless stated otherwise. Mass spectra were recorded on a
Shimadzu GCMS-QP505A spectrometer at 70 eV [probe; electron ion-
ization (EI)] and a Micromass QUATTRO II (ESI). Specific rotations
were measured using a JASCO DIP-1000 polarimeter and are given in
2,5-Dichlorobenzoquinone (21) (128 mg, 0.723 mmol) and (R)-(–)-
diene (2) (0.30 g, 0.87 mmol) in benzene (2 mL) were heated in a sealed
tube at 145◦C for 3 h. After removal of the solvent under reduced pres-
sure PLC (dichloromethane/toluene, 4 : 1) gave three yellow bands.
The most mobile (RF 0.65) contained 2,5-dichlorobenzoquinone
(21) (30 mg). The second yellow band (RF 0.55) gave (R)-(–)-
dichloronaphthoquinone (23) (45 mg, 13%) as a yellow oil, [α]D −30.2
(c 0.56 in CHCl3). υmax/cm−1 2950, 1732, 1681, 1578, 1241, 1221, 836.
λmax (EtOH)/nm 209 (log ε 4.88), 259 (4.67), 278 (4.64), 360 (3.88).
δH (400 MHz) −0.29 and −0.08 (2 × 3 H, 2 × s, 2 × SiMe), 0.77 (9 H,
s, SiCMe3), 1.19 (3 H, d, J 5.9, 2ꢀ-Me), 2.76 (2 H, m, H1ꢀ), 3.91 and
3.96 (2 × 3H, 2 × s, 2 × OMe), 4.06 (1 H, m, H2ꢀ), 7.95 (1 H, s, H4). δC
(100 MHz) −5.2 and −4.8 (2 × SiMe), 17.8 (SiCMe3), 24.3 (C2ꢀ-Me),
25.7 (SiCMe3), 43.9 (C1ꢀ), 52.7 (CO2Me), 63.5 (1-OMe), 68.5 (C2ꢀ),
units of 10−1 deg cm2 g−1
.
Materials
Thin-layer chromatography (TLC) and preparativeTLC (PLC) were per-
formed on Merck pre-coated silica gel 60 F254and Merck Kieselgel 60
GF254 (20 g silica gel spread on 20 × 20 cm2 glass plates), respectively.
Visualization was under ultraviolet light (254 or 366 nm).
121.0, 127.3(C4), 132.1, 137.4, 142.0, 144.9, 145.8, 158.3, 166.5, 173.6,
•
175.6. Mass spectrum (EI, 70 eV) m/z 433 (0.3%, [M – C4H9]+
,
37Cl2),
•
•
431 (1, [M – C4H9]+
,
37Cl35Cl), 429 (2, [M – C4H9]+
,
35Cl2), 287
Methyl (R)-(–)-5-tert-Butyldimethylsilyloxy-2-dimethoxymethylene-3-
methylenehexanoate (2)
(28), 159 (45), 89 (135), 85 (67), 83 (100), 73 (60). Mass spectrum
•
(EI, 20 eV) m/z 433 (5%, [M – C4H9]+
,
37Cl2), 432 (20), 431 (20,
The (R)-(–)-hexynoate (1) (1.8 g, 7.02 mmol), prepared as described
previously,[1] and ketene dimethyl acetal (0.80 g, 9.08 mmol) were
heated together in a sealed tube at 165◦C for 24 h. Kügelrohr distil-
lation yielded the (R)-diene (2) (0.35 g, 43%) and unchanged acetylene
(1) (1.2 g). The (R)-(–)-diene (2) was obtained as a pale yellow oil,
[α]D −21.8 (c 0.52 in CHCl3), b.p. 140–145◦C/0.15 mmHg (Found: [M
– C4H9]+•, 287.1320. C13H23O5Si requires [M – C4H9]+•, 287.1315).
υmax/cm−1 2950, 2853, 1733, 1642, 1254, 1214, 759. δH (400 MHz)
0.03 (6 H, s, 2 × SiMe), 0.86 (9 H, s, SiCMe3), 1.14 (3 H, d, J 6.1, H6),
2.18 (1 H, dd, J 8.9 and 13.8, H4A), 2.49 (1 H, dd, J 4.4 and 13.8, H4B),
3.67 (3 H, s, OMe), 3.83 (3 H, s, OMe), 3.83 (3 H, s, CO2Me), 3.85 (1 H,
m, H5), 4.89 (1 H, br s, =CH2), 5.09 (1 H, br s, =CH2). Mass spectrum
•
•
[M – C4H9]+
,
37Cl35Cl), 430 (80), 429 (27, [M – C4H9]+
,
35Cl2), 428
(100), 398 (22), 396 (31), 324 (24), 322 (34), 159 (50), 89 (30), 73
(21). Mass spectrum [fast-atom bombardment (FAB)] m/z 433 (12%,
•
•
[M – C4H9]+
,
37Cl2), 431 (16, [M – C4H9]+
,
37Cl35Cl), 429 (22, [M –
•
C4H9]+
,
35Cl2), 327 (35), 321 (23), 295 (27), 279 (37), 239 (29), 237
(100), 232 (51), 221(41), 217 (36), 216 (16), 215 (94), 214 (86), 199
(31), 197 (86), 181 (78), 179 (43), 165 (27), 159 (31).
The least mobile yellow band (RF 0.42 in dichloromethane/ toluene,
4 : 1) was further chromatographed using a graded solvent system of
ether/light petroleum to give (R)-(–)-naphthoquinone (22) (52 mg, 16%)
as a yellow oil (RF 0.65 in ether/light petroleum, 1 : 1), [α]D −11.7 (c
0.66 in CHCl3) (Found: [M + Na]+•, 475.1336. C22H29 35ClNaO6Si
requires [M + Na]+•, 475.1320). υmax/cm−1 2950, 1733, 1678, 1657,
1241, 836. λmax (EtOH)/nm 209 (log ε 4.88), 249 (4.55), 275 sh (4.40),
354 (3.94). δH (400 MHz) −0.28 and −0.08 (2 × 3H, 2 × s, 2 × SiMe),
0.78 (9 H, s, SiCMe3), 1.19 (3 H, d, J 5.9, 2ꢀ-Me), 2.76 (2 H, m, H1ꢀ),
3.89 and 3.96 (2 × 3H, 2 × s, 2 × OMe), 4.06 (1 H, m, H2ꢀ), 7.14 (1 H, s,
H7), 7.93 (1 H, s, H4). δC (100 MHz) −5.2 and −4.8 (2 × SiMe), 17.8
(SiCMe3), 24.3 (C2ꢀ-Me), 25.7 (SiCMe3), 43.9 (C1ꢀ) 52.7 (CO2Me),
63.5 (1-OMe), 68.5 (C2ꢀ) 121.8, 127.0 (C4), 132.6, 137.3, 137.6, 144.4,
•
(EI) m/z 344 (1%, M+ ), 287 (42, [M – C4H9]+•), 159 (31), 105 (27),
89 (67), 75 (37), 73 (100).
Reaction of the ( )-Diene (2) and 2-Chloro-
5-methoxybenzoquinone (15)
2-Chloro-5-methoxybenzoquinone (15) (96 mg, 0.84 mmol) and ( )-
diene (2) (0.25 g, 0.87 mmol) in toluene (1 mL) were heated at reflux
for 22 h and the solvent was removed under reduced pressure. PLC
using a graded solvent system of dichloromethane/ethyl acetate gave
two products. The less mobile band (RF 0.25 in dichloromethane/ethyl
acetate, 95 : 5) gave ( )-naphthoquinone (14) (14 mg, 6%) as a yel-
low oil (Found: [M – C4H9]+•, 391.1216. C19H23O7Si requires [M –
C4H9]+•, 391.1213). υmax/cm−1 2927, 1727, 1678, 1647, 1617, 1585,
1263, 1233, 739, 704. λmax (EtOH)/nm 208 (log ε 4.30), 245 (4.09), 277
(3.71) 291 (3.56), 342 (3.42). δH (400 MHz) −0.28 and −0.09, (2 × 3 H,
2 × s, 2 × SiMe), 0.78 (9 H, s, SiCMe3), 1.18 (3 H, d, J 6.1, s, 2ꢀ-Me),
2.74 (2 H, m, H1ꢀ), 3.88, 3.89 and 3.95 (3 × 3 H, 3 × s, 3 × OMe), 4.03
(1 H, m, H2ꢀ), 6.10 (•1 H, s, H 7), 7.90 (1 H, s, H 4). Mass spectrum (EI)
m/z 448 (0.5%, M+ ), 392 (36), 391 (100, [M – C4H9]+•), 359 (56),
285 (68), 159 (35), 115 (27), 103 (22).
The more mobile band (RF 0.48 in dichloromethane/ethyl acetate,
95 : 5) gave product (18) (160 mg, 59%) as a pale yellow oil
(Found: [M + Na]+•, 507.1570. C23H3335ClNaO7Si requires [M +
Na]+•, 507.1582). υmax/cm−1 3362, 2950, 1698, 1592, 1432, 1407,
1332, 1313, 1252, 1206, 1102, 997, 835, 756. δH (300 MHz) −0.16 and
−0.05 (2 × 3 H, 2 × s, 2 × SiMe), 0.78 (9 H, s, SiCMe3), 1.09 (3 H, d,
J 5.9, 2ꢀ-Me), 2.61 (1 H, dd, J, 8.2 and 13.5, H1Aꢀ ), 2.72 (1 H, dd, J
5.2 and 13.5, H1ꢀB), 3.76, 3.80 and 4.06 (3 × 3 H, 3 × s, 3 × OMe), 4.13
(1 H, m, H2ꢀ), 6.61 (1 H, s, H 7), 7.60 (1 H, s, H4). δC (75 MHz) −4.96
and −4.93 (2 × SiMe), 18.0 (SiCMe3), 24.0 (C2ꢀ-Me), 25.8 (SiCMe3),
34.8 (Clꢀ), 50.9, 55.9, 57.6, 68.4 (C2ꢀ), 91.7, 99.9 (C7), 110.7, 112.6,
145.0, 157.5, 166.7, (CO2Me), 1•77.6 (C5), 180.8 (C8). Mass spectrum
•
(EI) m/z 397 (32%, [M – C4H9]+
,
37Cl), 395 (68, [M – C4H9]+
,
35Cl),
363 (45), 289 (50), 159 (22), 89 (72), 75 (51), 73 (100).
(
)-7-Chloro-10-methoxy-3-methyl-3,4-dihydro-1H-naphtho
[2,3-c]pyran-1,6,9-trione (25)
To a solution of the ( )-naphthoquinone (22) (40 mg, 0.088 mmol)
in dichloromethane (6 mL) was added para-toluenesulfonic acid
(10 mg) and the mixture was stirred at room temperature for 48 h.
The solution was diluted with water (5 mL) and extracted with
dichloromethane (3 × 10 mL).The combined extracts were washed with
water (3 × 10 mL), dried (MgSO4) and concentrated under reduced
pressure. PLC (toluene/ethyl formate/formic acid, 50 : 49 : 1, RF 0.63)
afforded the ( )-lactone (25) (19 mg, 70%) as yellow needles, m.p.
176–178◦C from ethyl acetate/light petroleum (Found: C, 58.6; H, 3.7%.
C15H11ClO5 requires C, 58.7, H, 3.6%). υmax/cm−1 1722, 1675, 1649,
1582, 1221, 1138, 1075. λmax (EtOH)/nm 212 (log ε 4.77), 265 (4.31),
364 (3.63). δH (400 MHz) 1.54 (3H, d, J 6.4, 3-Me), 3.01 (1 H, dd, J 9.9
and 16.6, H4ax), 3.07 (1 H, dd, J 3.9 and 16.6, H4eq), 4.05 (3 H, s, OMe),
4.61 (1H, m, H3), 7.18 (1 H, s, H8), 7.84 (1 H, s, H5). δC (100 MHz)
20.5 (3-Me), 36.4 (C4), 63.7 (OMe), 74.2 (C3), 121.9, 124.2, 125.7,
135.5, 138.2, 143.8, 147.5, 160.3, 162.9, 177.7 (C5), 180.3 (C8). Mass