2330
J . Org. Chem. 1997, 62, 2330-2331
Sch em e 1a
In tr a m olecu la r Diels-Ald er a n d Cop e
Rea ction s of o-Qu in on oid Mon ok eta ls a n d
Th eir Ad d u cts: Efficien t Syn th eses of
(()-Xestoqu in on e a n d Heter ocycles Rela ted
to Vir id in
Rina Carlini, Kerianne Higgs, Christina Older, and
Sab Randhawa
Guelph-Waterloo Center for Graduate Work in Chemistry,
University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
a
Conditions: (a) 1.2 equiv of PhI[O2CCF3]2, 5 equiv of (E)-2,4-
pentadienol, 2.4 equiv of NaHCO3(s), 2 mol % of BHT (for 4a ), dry
THF, rt; (b) distill excess 2,4-pentadienol (bp ) 58 °C/20 mmHg).
Russell Rodrigo*
Department of Chemistry, Wilfrid Laurier University,
Waterloo, Ontario N2L 3C5, Canada
o-methoxyphenols 4a -c in the presence of an excess
amount of (E)-2,4-pentadienol (Scheme 1). The intramo-
lecular Diels-Alder (IMDA) reaction that followed would
compel the o-quinonoid monoketal to react as a diene5
(to form 6) and/or as a dienophile (to form 7). The former
pathway is predictably favored because of the o-quinonoid
s-cis geometry, but we had hoped that the latter reaction,
hitherto unprecedented, could be encouraged by the
placement of electron-withdrawing substituents at C-4
of 4 to enhance dienophilicity of the o-quinonoid inter-
mediate 5. The results (Scheme 1) vindicated our think-
ing, but mixtures of 6 and 7 were always produced, and
to tip the balance completely toward dienophilic reactiv-
ity, the unsubstituted double bond had to be removed
from the game, and this could be done by making it part
of an aromatic ring.
Thus, four substrates, three naphthalenoid 9a -c and
one anthracenoid 12a , prepared from the corresponding
o-methoxyphenols 8a -c and 11a provided good to excel-
lent yields of the desired adducts 10a -c and 13a formed
as endo-exo6 mixtures (Scheme 2). All these reactions
are “one-pot” three-step double annelation processes
(oxidation, ketalization, and IMDA), and yields reported
are for pure isolated materials. Furthermore, the same
reaction with the tricyclic benzindanone substrate 15
produced 16 in 86% yield (2:1 endo-exo). Adduct 16
represents the first ever construction of the pentacyclic
system of viridin and could be regarded as an advanced
intermediate for the eventual synthesis of this compound.
Although this new IMDA dienophilic reactivity of o-
quinonoid species appeared to be general,7 the reaction
failed with 8d ; only red polymeric material was produced,
probably through the formation of a p-quinomethide in
the oxidation step. It is interesting but hardly surprising
that the 9,10-dihydroanthraquinonoid ketal 12b behaved
like o-benzoquinonoid ketal 5c, providing a mixture of
14 (32%) and the 7,12-dihydroderivative 13b (23%, as the
endo isomer only).
Received March 4, 1997
The viridin (1) family of steroidal antibiotics1 as well
as the xestoquinone (2a ) and halenaquinone (2b) groups
of marine natural products are pentacyclic compounds
featuring a common naphtho[1,8-bc]furanone unit with
an “angular” methyl group. Synthetic activity in this
area has resulted2 in many syntheses of 2a and 2b, but
there have been no reports of any such success with the
more challenging targets like viridin and its congeners,
even though this group of antifungal agents have been
known for much longer. The best synthesis3 to date of a
tricyclic naphthofuranone furnished 3 in 11 steps and
6.3% overall yield from R-furylmethanol. Although this
work culminated in the synthesis of 2a (1.5% overall, 14
steps), it was not efficient enough to be realistically
regarded as a gateway to the viridin group of natural
products. Our initial synthetic efforts4 toward a tricycle
like 3 were not successful, but their failure forced us to
reexamine the problem and to look for a more direct route
to this deceptively simple compound. Not only would
success in this venture permit the development of a rapid
synthesis of 2a and 2b, but it would also allow explora-
tions to commence toward a first synthesis of viridin.
The formal similarity of the R-oxygenated cyclohexa-
dienone moiety of 3 to o-benzoquinone prompted an
investigation into the Diels-Alder chemistry of those
highly reactive substrates. To ensure regiocontrol in the
cycloaddition and to restrain the facile polymerization
processes that plague the chemistry of simple o-benzo-
quinones, an intramolecular version of the reaction was
considered. The test vehicles chosen for this purpose
were mixed monoketals of o-quinones 5a -c that could
be easily generated in situ by oxidation of the respective
A reevaluation of the results of the IMDA reaction with
the o-benzoquinonoid substrates 5 showed that the
(5) (a) Yamamura, S.; Shizuri, Y.; Shigemori, H.; Okuno, Y.; Okhubo,
M. Tetrahedron 1991, 47, 635-644. (b) Chu, C.-S.; Lee, T.-H.; Liao,
C.-C. Synlett 1994, 635-6.
(6) All the IMDA reactions were face selective and endo with respect
to the o-quinonoid ring.
(7) A 1,3-cyclohexadiene-5,6-diol carrying a pendant diene unit at
the C-5 hydroxyl group produced only the bridged adduct in the IMDA
reaction: Hudlicky, T.; Boros, C. H.; Boros, E. E. Synthesis 1992, 174-
6. We thank a reviewer for bringing this to our attention.
(8) X-ray crystal structures have been obtained for 10a (exo and
endo) and 1H and 13C NMR correlations made with the tricyclic
moieties of the other adducts. An important diagnostic feature emerged
when a small W-coupling of 2.2 Hz between H-1â and H-10c (estab-
lished by decoupling and 2D correlation) was observed in the endo
isomer of 10a . This coupling is found in every other endo isomer of
the tricyclic unit but is absent in every exo isomer.
(1) For a recent review see: Hanson, J . R. Nat. Prod. Rep. 1995,
12, 381-4.
(2) (a) Maddaford, S. P.; Anderson, N. G.; Cristofoli, W. A.; Keay,
B. A. J . Am. Chem. Soc. 1996, 118, 10766-73 and references therein.
(b) Harada, N.; Sugioka, T.; Uda, H.; Kuriki, T.; Kobayashi, M.;
Kitagawa, I. J . Org. Chem. 1994, 59, 6606-13.
(3) Kanematsu, K.; Soejima, S.; Wang, G. Tetrahedron Lett. 1991,
32, 4761-4.
(4) Burns, P. A.; Taylor, N. J .; Rodrigo, R. Can. J . Chem. 1994, 72,
42-50.
S0022-3263(97)00394-0 CCC: $14.00 © 1997 American Chemical Society