(trimethylsilyl)amide [NaN(TMS)2] followed by carbon
disulfide and then iodomethane afforded the corresponding
methyl xanthate 12 in 94% yield, which was further treated
with tri-n-butyltin hydride and 2,2′-azobis(isobutyronitrile)
(AIBN) in refluxing toluene, providing the desired deoxy-
genated product 13 in 77% yield. Compound 13 was then
converted to the requisite phenolic segment 5 in 92% overall
yield via a two-step sequence involving acid hydrolysis of
both the MOM and ethylene acetal protecting groups in 13
followed by reprotection of the carbonyl functionality of the
resulting ketone 14.12
product 15, methyl xanthate 16, deoxygenated product 17,
and ketone 18. The subsequent crucial formation of the
quinone system was successfully carried out by reaction of
19 with molecular oxygen in the presence of salcomine [N,N-
bis(salicylidene)ethylenediiminocobalt(II)]14 in DMF at am-
bient temperature, which provided the corresponding quinone
20 in 85% yield. Finally, dichlorination of 20 was achieved
by treatment with thionyl chloride in the presence of pyridine
in refluxing benzene,15 leading to the formation of the desired
quinone segment 6 in 78% yield.
With the phenolic segment 5 and the quinone segment 6
in hand, we turned our attention toward the proposed
biogenetic-type annulation to construct the central tricyclic
ring system of the targeted compound 1 as depicted in
Scheme 4. The critical annulation of 5 with 6 was ac-
Next, the synthesis of the quinone segment 6 was
conducted through the coupling reaction of the cis-decalin
7 with 1-bromo-2-methoxy-6-(methoxymethoxy)benzene (9)13
as shown in Scheme 3. By employing a reaction sequence
Scheme 3. Synthesis of the Quinone Segment 6a
Scheme 4. Synthesis of 8-O-Methylpopolohuanone E (2)a
a Reagents and conditions: (a) 1-bromo-2-methoxy-6-(meth-
oxymethoxy)benzene (9), n-BuLi, THF, -40 °C; 7, -40 f -20
°C, 97%; (b) CS2, THF, -78 °C; NaN(TMS)2, -78 f -70 °C;
MeI, -70 f -60 °C, 90%; (c) n-Bu3SnH, AIBN, toluene, reflux,
81%; (d) 12 M HCl, MeOH, 40 °C, 95%; (e) (CH2OH)2, p-TsOH,
benzene, reflux, 90%; (f) salcomine, O2, DMF, rt, 85%; (g) SOCl2,
pyridine, benzene, reflux, 78%.
a Reagents and conditions: (a) 5, NaH, THF, rt; 6, -78 °C, 94%;
(b) Amberlite IRA-900, THF, rt, 80%; (c) 1.0 M HCl, MeOH, rt,
100%; (d) CH2Br2, Zn, TiCl4, THF, rt, 26%; (e) n-BuSLi, HMPA,
110 °C, 34%.
similar to that described for the synthesis of the phenolic
segment 5, the phenol derivative 19 was prepared starting
with 7 in five steps in 60% overall yield via the coupling
complished in a completely regioselective manner via a two-
step sequence of reactions. Thus, the initial coupling reaction
of 5 with 6 in the presence of sodium hydride in THF at
-78 °C proceeded smoothly to provide the coupling product
(11) Barton, D. H. R.; McCombie, S. W.J. Chem. Soc., Perkin Trans. 1
1975, 1574.
(12) Direct conversion of compound 13 to the requisite phenolic segment
5 by chemoselective deprotection of the MOM protecting group met with
failure.
(13) Compound 9 was prepared from commercially available 3-meth-
oxyphenol via a two-step sequence of reactions [(a) MOMCl, i-Pr2NEt,
CH2Cl2, rt, 91% (b) t-BuLi, TMEDA, Et2O, -78 °C.; Br2, -78f0 °C,
73%] (see the Supporting Information for experimental details). Compound
9 has been previously prepared from the same starting material using 1,2-
dibromotetrafluoroethane as the bromine source, see: Rice, J. E.; Cai, Z.-
W. J. Org. Chem. 1993, 58, 1415.
(14) (a) Wakamatsu, T.; Nishi, T.; Ohnuma; T.; Ban, Y. Synth. Commun.
1984, 14, 1167. (b) Yoshida, K.; Nakajima, S.; Ohnuma, T.; Ban Y.;
Shibasaki, M.; Aoe, K.; Date, T. J. Org. Chem. 1988, 53, 5355. (c) Saito,
N.; Obara, Y.; Aihara, T.; Harada, S.; Shida, Y.; Kubo, A. Tetrahedron
1994, 50, 3915. (d) Miyata, F.; Yoshida, S.; Yamori, T.; Katoh, T.
Heterocycles 2001, 54, 619.
(15) Shi, S.; Katz, T. J.; Yang, B. V.; Liu, L. J. Org. Chem. 1995, 60,
1285.
Org. Lett., Vol. 3, No. 17, 2001
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