PAPER
Synthesis of Magnoshinin and Cyclogalgravin
1559
Dihydronaphthalene Alcohol 9a
13C NMR (CDCl3): = 23.0, 33.1, 35.3, 47.6, 56.1, 56.2, 56.3, 57.0,
57.2, 60.9, 96.3, 98.6, 114.1, 116.6, 117.9, 123.2, 129.1, 133.2,
141.7, 142.8, 148.3, 151.2, 151.3, 152.6.
MS: m/z (%) = 494 (M+, 33), 412 (100), 397 (52), 245 (92), 181
(69).
Dihydronaphthalene diol 8a (0.447 g, 1 mmol) was dissolved in
freshly distilled THF (15 mL) in a flask flushed with N2 and cooled
to –78 °C. PBr3 (0.201 mg, 0.74 mmol) in THF (2 mL) was added,
the solution stirred at –78 °C for 1 h, then a slurry of LAH (80 mg,
2.1 mmol) in THF (4 mL) was added to the reaction mixture. The
mixture was slowly warmed to 0 °C (1.5 h), refluxed for 25 min, and
then worked up using Fieser’s method.29 In succession, H2O (0.35
mL), 15% NaOH (0.35 mL) and H2O (0.9 mL) were added to the
reaction mixture followed by EtOAc. The solution was dried
(MgSO4), filtered, and stripped of solvent under reduced pressure to
give an oil (0.40 g). The crude reaction mixture was purified by
flash silica gel column chromatography (50–70% EtOAc–hexanes).
The conjugated alcohol (0.309 g, 72%) was obtained as a pale yel-
low oil that slowly crystallized.
HRMS: m/z calcd for C24H29O681Br: 494.1127. Found: 494.1117.
Dihydronaphthalene Bromide 10b
Alcohol 9b (50 mg, 0.135 mmol) was brominated in THF (5 mL)
using PBr3 (100 mg, 0.369 mmol) in THF (1 mL) as described
above to give a yellow oil (31 mg, 53%) after chromatography.
1H NMR (CDCl3): = 1.81 (d, 3H, J = 1.2 Hz), 2.62 (dt, 1H, J = 2.7,
10.4 Hz), 3.15 (t, 1H, J = 10.4 Hz), 3.51 (dd, 1H, J = 3.2, 10.1 Hz),
3.78 (s, 3H), 3.81 (s, 3H), 3.82 (s, 3H), 3.88 (s, 3H), 4.33 (d, 1H, J
= 2.1 Hz), 6.27 (br s, 1H), 6.53 (dd, 1H, J = 2.0, 8.2 Hz), 6.63 (br s,
3H), 6.71 (d, 1H, J = 8.3 Hz).
Mp 128.0–130.0 °C (hexane–EtOAc).
1H NMR (CDCl3): = 1.77 (d, 3H, J = 1.4 Hz), 2.37 (dd, 1H, J =
4.5, 8.6 Hz), 3.39 (s, 3H), 3.42 (dd, 1H, J = 8.6, 10.5 Hz), 3.56 (s,
3H), 3.64 (dd, 1H, J = 4.5, 10.5 Hz), 3.84 (s, 6H), 3.85 (s, 3H), 3.92
(s, 3H), 4.98 (s, 1H), 6.25 (s, 1H), 6.41 (s, 1H), 6.53 (s, 1H), 6.63 (d,
1H, J = 1.4 Hz).
13C NMR (CDCl3): = 22.2, 35.2, 45.3, 55.8 (2 CH3), 55.94, 55.96,
109.2, 111.0, 113.1, 119.7, 124.4, 126.0, 126.4, 133.0, 136.6, 147.5,
148.0, 148.2, 148.7.
MS: m/z (%) = 434 (M+, 8), 432 (M+, 10).
13C NMR (CDCl3): = 23.4, 31.7, 49.3, 56.1, 56.2, 56.3, 57.0, 57.1,
60.5, 64.1, 96.3, 98.2, 114.0, 117.0, 117.3, 124.6, 129.6, 132.6,
141.3, 142.8, 148.0, 150.5, 151.0, 152.1.
HRMS: m/z calcd for C22H25O479Br: 432.0936. Found: 432.0917.
Magnoshinin 1a
MS: m/z (%) = 430 (M+, 41), 412 (100), 399 (76), 397 (50), 384
(37), 352 (35).
A solution of 10a (63 mg, 0.127 mmol) and tri-n-butyltin hydride
(0.2 mL, 0.74 mmol) in toluene (5 mL) was refluxed under N2 for
12 h. Evaporation of the solvent in vacuo and chromatography on
silica gel (50% EtOAc–hexanes) gave a colorless oil (53 mg, 99%).
HRMS: m/z calcd for C24H30O7: 430.1991. Found: 430.1949.
The 1H NMR (CDCl3) spectrum was identical with that previously
Dihydronaphthalene Alcohol 9b
published.23
Dihydronaphthalene diol 8b (0.182 g, 0.471 mmol) in THF (5 mL)
was brominated (PBr3, 0.113 g, 0.417 mmol) and reduced (LAH,
0.045 g, 1.186 mmol) as described above to give a colorless oil
(0.113 g, 64%).
13C NMR (CDCl3): = 19.1, 22.8, 36.8, 40.6, 56.11, 56.17, 56.4,
56.9, 57.1, 60.6, 96.2, 98.2, 113.9, 114.2, 117.4, 125.2, 130.0,
138.7, 141.6, 142.7, 147.8, 150.79, 150.84, 151.8.
1H NMR (CDCl3): = 1.79 (d, 3H, J = 1.4 Hz), 2.47 (ddd, 1H, J =
1.8, 4.2, 8.8 Hz), 3.43 (dd, 1H, J = 8.8, 10.7 Hz), 3.68 (dd, 1H, J =
4.2, 10.7 Hz), 3.77 (s, 3H), 3.77 (s, 3H), 3.80 (s, 3H), 3.87 (s, 3H),
4.16 (d, 1H, J = 1.8 Hz), 6.25 (d, 1H, J = 1.4 Hz), 6.53 (dd, 1H, J =
2.04, 8.3 Hz), 6.61 (s, 2H), 6.63 (d, 1H, J = 2.04 Hz), 6.69 (d, 1H, J
= 8.3 Hz).
13C NMR (CDCl3): = 22.7, 44.5, 50.9, 55.78, 55.8, 55.87, 55.91,
62.9, 109.2, 111.0, 112.9, 119.5, 123.8, 126.82, 126.95, 133.1,
137.8, 147.3, 147.7, 147.9, 148.7.
MS: m/z (%) = 414 (M+, 100), 399 (16), 384 (21), 383 (36), 368
(32), 246 (22), 231 (39).
HRMS: m/z calcd for C24H30O6: 414.2042. Found: 414.2029.
Cyclogalgravin 1b
Dihydronaphthalene bromide 10b (0.030 g, 0.069 mmol) was re-
duced with tri-n-butyltin hydride (1.1 mL, 0.402 mmol) in toluene
(5 mL) as described above to give a colorless oil (20.9 mg, 85%) af-
ter chromatography (40% EtOAc–hexanes).
MS: m/z (%) = 370 (M+, 43), 352 (20), 339 (100), 324 (23), 308
(19).
1H NMR (CDCl3): = 1.08 (d, 3H, J = 7.1 Hz), 1.80 (d, 3H, J = 1.4
Hz), 2.38 (dq, 1H, J = 3.2, 7.1 Hz), 3.67 (d, 1H, J = 3.2 Hz), 3.777
(s, 3H), 3.780 (s, 3H), 3.82 (s, 3H), 3.88 (s, 3H), 6.14 (br, 1H), 6.558
(s, 1H), 6.55 (dd, 1H, J = 2.0, 8.1 Hz), 6.62 (s, 1H), 6.66 (d, 1H, J =
2.0 Hz), 6.71 (d, 1H, J = 8.1 Hz).
HRMS: m/z calcd for C22H26O5: 370.1780. Found: 370.1768.
Dihydronaphthalene Bromide 10a
The 13C NMR (CDCl3) spectrum was identical to that previously
A solution of dihydronaphthalene alcohol 9a (50 mg, 0.116 mmol)
in freshly distilled THF (3 mL) was warmed to 60 °C and a solution
of PBr3 (25 mg, 0.092 mmol) in THF (1 mL) was added. The solu-
tion was stirred at 60 °C under N2 for 1 h. The reaction mixture was
cooled to r.t., 5% NaHCO3 (2 mL) was added, and the mixture ex-
tracted with EtOAc (3 10 mL). The combined organic layers were
washed with brine, dried (MgSO4), and concentrated in vacuo.
Chromatography on silica gel (30–50% EtOAc–hexanes) gave a
solid (28 mg, 49%).
published.28
MS. m/z (%) = 354 (M+, 100), 352 (14), 340 (13), 339 (57), 324
(20), 308 (15), 216 (17), 165 (16).
HRMS: m/z calcd for C22H26O4: 354.1831. Found: 354.1833.
Acknowledgement
Mp 144.0–146.0 °C (hexane–EtOAc).
The financial assistance of the Natural Sciences and Engineering
Research Council of Canada is gratefully acknowledged.
1H NMR (CDCl3): = 1.76 (d, 3H, J = 1.5 Hz), 2.57 (ddd, 1H, J =
1.0, 3.9, 10.6 Hz), 3.09 (dd, 1H, J = 10.2, 10.6 Hz), 3.47 (dd, 1H, J
= 3.9, 10.2 Hz), 3.53 (s, 3H), 3.54 (s, 3H), 3.84 (s, 3H), 3.857, (s,
3H), 3.86 (s, 3H), 3.93 (s, 3H), 5.20 (d, 1H, J = 1.0 Hz), 6.18 (s, 1H),
6.42 (s, 1H), 6.52 (s, 1H), 6.62 (q, 1H, J = 1.5 Hz).
References
(1) Ayres, D. C.; Carpenter, B. G.; Denney, J. J. Chem. Soc.
1965, 3578.
Synthesis 2001, No. 10, 1556–1560 ISSN 0039-7881 © Thieme Stuttgart · New York