Synthesis of endo,endo-2.9-dihydroxypentacyclo-[8.4.0.03,8. 04,14.07,11]tetradeca-5,12-diene

Article abstract of DOI:10.1002/jccs.200800026

The title compound 30 was synthesized starting from the endo,syn,endo Diels-Alder adduct 3a of hexahydro-5,6,7,8-tetrachloro-9,9-dimethoxy-5,8- methanonaphthalene-1,4-diol diacetate 6 and 1,2,3,4-tetrachloro-5,5- dimethoxycyclopentadiene (TDCp) in six steps, keyed upon a symmetry-allowed [4+4] photocyclization of decahydro-11,12-dioxo-[1,4;5,8]dimethanoanthracene-9, 10-diol diacetate 22. The epimeric monoacetate 26 related to 22 was also synthesized and their thermolysis and photolysis were investigated. Oxidation of diol 30 afforded hexacyclic bridged hemiacetal 31 as a result of transannular reaction. The structure of hemiacetal 31 was analyzed by single-crystal X-ray crystallography.

Full text of DOI:10.1002/jccs.200800026

Journal of the Chinese Chemical Society, 2008, 55, 171-182
171
Synthesis of endo,endo-2.9-Dihydroxypentacyclo-
[8.4.0.03,8.04,14.07,11]tetradeca-5,12-diene
Teh-Chang Chou* (
Sen-Ching Wu (
Department of Chemistry and Biochemistry, National Chung Cheng University,
), Gerng-Horng Lin (
),
) and Sushilkumar S. Bahekar
Minsyong, Chiayi, 621, Taiwan, R.O.C.
The title compound 30 was synthesized starting from the endo,syn,endo Diels-Alder adduct 3a of
hexahydro-5,6,7,8-tetrachloro-9,9-dimethoxy-5,8-methanonaphthalene-1,4-diol diacetate 6 and 1,2,3,4-
tetrachloro-5,5-dimethoxycyclopentadiene (TDCp) in six steps, keyed upon a symmetry-allowed [4+4]
photocyclization of decahydro-11,12-dioxo-[1,4;5,8]dimethanoanthracene-9,10-diol diacetate 22. The
epimeric monoacetate 26 related to 22 was also synthesized and their thermolysis and photolysis were in-
vestigated. Oxidation of diol 30 afforded hexacyclic bridged hemiacetal 31 as a result of transannular re-
action. The structure of hemiacetal 31 was analyzed by single-crystal X-ray crystallography.
Keywords: 1,2,3,4-Tetrachloro-5,5-dimethoxycyclopentadiene; Diels-Alder reaction; Polycyclic
compounds; Cage compounds.
INTRODUCTION
Scheme I
Cl
Cl
Cl
R
R'
OCH3
H3CO
The Diels-Alder reaction of 1,2,3,4-tetrachloro-5,5-
dimethoxycyclopentadiene (TDCp)1 and 1,4-cyclohex-
adiene produced a 2:1 adduct 1a.2 Its endo,syn,endo stereo-
structure, rather than the endo,anti,endo 1b, is evident from
1H NMR spectrum2b and later confirmed by chemical trans-
formations.3-5 As illustrated in Scheme I, the initially
formed 1:1 endo adduct 4 presumably adopts the sterically
more favored “unfolded” boat-conformation (4a), which
allows the cycloaddition to occur at the less sterically de-
manding p-face syn to the existing dichlorinated double
bond, resulting in the formation of endo,syn,endo adduct
1a.2 However, this mode of p-facial selectivity was not ob-
served in our attempt to synthesize endo,syn,endo-diol 2a
via the Diels-Alder reaction of TDCp with endo,endo-diol
56 derived from CeCl3-mediated NaBH4 reduction of the
Diels-Alder adduct of 1,4-benzoquinone and TDCp. The
Diels-Alder reaction afforded instead the endo,anti,endo
adduct 2b as sole product in 85% yield.7 Presumably,
endo,endo-diol 5 preferably adopts the “folded” boat-con-
formation (5b), instead of the more sterically crowded “un-
folded” boat-conformation (5a), in which the two face-to-
face hydroxyl groups occupy the concave position and are
in proximity to the dichlorinated double bond. Further-
R
Cl
Cl
R
H3CO
OCH3
Cl
H3CO
OCH3
H3CO
R'
Cl
Cl
Cl
R'
Cl
R
Cl
Cl
Cl
R'
OCH3
Cl
Cl
Cl
1: R = R' = H
a
(endo,syn,endo)
b
2: R = H; R' = OH
3: R = OH; R' = H
(endo,anti,endo)
(2b = 3b)
OCH3
Cl
H3CO
Cl
Cl
TDCp
Cl
H3CO
H
H
H3CO
R
H
R'
R
Cl
Cl
H
H3CO
H3CO
R
Cl
Cl
Cl
Cl
R'
Cl
R'
R
R'
Cl
4: R = R' = H
5: R = H; R' = OH
6: R = OH; R' = H
anti
syn
a
b
TDCp
4b
4a
1a
3a
(ref. 2-5)
TDCp
5b
6b
2b
5a
6a
xylene, reflux
TDCp
2 d
85%
CaCO3,
125 oC, 4 d
82%
more, both p-faces in conformation 5a are sterically hin-
dered due to the hydroxyl groups and ring-junction hydro-
* Corresponding author. Tel: +886-5-2428116; Fax: +886-5-272 1040; E-mail: chetcc@ccu.edu.tw

172 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Chou et al.
gens, and hence the Diels-Alder reaction of 5 occurs at the
anti p-face (opposite to the dichlorinated double bond) of
the conformation 5b to yield endo,anti,endo-diol 2b. It was
believed that inverting the configuration of a carbon atom
bearing a hydroxyl group could reverse the conformational
preference8 and hence the conformation-controlled p-fa-
cial selectivity in the Diels-Alder reaction. The resulting
exo,exo-diol 6 would employ the more stable and sterically
less demanding “unfolded” boat-conformation 6a to un-
dergo a syn cycloaddition with TDCp to furnish endo,syn,
endo-diol 3a, instead of the “folded” boat-conformation
6b, where both p-faces are sterically more demanding due
to the hydroxyl groups and the dichlorinated double bond.
This speculation led us7 and another9 to successfully pre-
pare exo,exo-diol 6 and Diels-Alder endo,syn,endo-diol
adduct 3a for use as starting materials in the synthesis of a
variety of novel polycyclic systems.
Scheme II
ative of pentacyclic diene 9, and is the main target molecule
pursued in this work. With this intention and investigating
the effects of the presence and configuration of acetoxy
groups on the thermolytic and photolytic behavior shown
in Scheme II, we also attempted, yet unsuccessfully, to syn-
thesize diacetoxy dione 27, which is the stereoisomer of
dione 22 having two acetoxy groups located inside the cav-
ity between the two etheno-bridge double bonds. This pa-
per describes the results.
Reductive dechlorination of 1a followed by acid-cat-
alyzed hydrolysis of ketal groups furnished pentacyclic
dione 7.3,4 As shown in Scheme II, upon irradiation in a
benzene solution, dione 7 was found3 to undergo sequential
decarbonylation with successive occurrences of a [4+2]
intramolecular Diels-Alder reaction and a symmetry-al-
lowed [4+4] photocyclization to afford hexacyclic enone 8
and pentacyclic diene 9 in 15% and 50% yields, respec-
tively. Thermolytic reaction of dione 7 resulted in the for-
mation of enone 8 in over 80% yield.3 In the presence of
maleic anhydride, thermolysis of dione 7 was accompanied
with a domino Diels-Alder reaction affording adduct 10,
which was used in this laboratory to synthesize C2v sym-
metric hexacyclic diene 11.4b In a continuation of our inter-
est in the synthesis and chemistry of polycyclic cage com-
pounds,4,10 we prepared endo,syn,endo-diol 3a and con-
verted it via a similar process of dechlorination-hydrolysis
followed by acetylation to decahydro-11,12-dioxo[1,4;5,8]-
dimethano anthracene-9,10-diol diacetate 22, the deriva-
tive of pentacyclic dione 7 (Scheme V). We thought the
products attained from 22 via photolysis and thermolysis,
having the ring skeletons as pentacyclic dienes 8, 9, and 11,
could be elaborated as precursors toward novel polycyclic
cage compounds related to iceane (12),11 the elusive hexa-
prismane (13),12 and hitherto unknown 14. Tetraene 14 is a
pentacyclic C16H16 hydrocarbon having two pairs of double
bonds orthogonally disposed. Conceptually, it is a dimer of
cyclooctatetraene (15) via a [2+2+2+2] cycloaddition and
synthetically it conceivably could be realized by ring ex-
pansion of pentacyclic dione 16, which is a diketonic deriv-
RESULTS AND DISCUSSION
The configurational inversion of carbon atoms bear-
ing hydroxyl groups in endo,endo-diol 56 to form exo,exo-
diol 6 was accomplished via two routes as outlined in
Scheme III. The Mitsunobu protocol13 (Ph3P, DEAD) uti-
lizing p-nitrobenzoic acid as the nucleophile was em-
ployed.7 Di-p-nitrobenzoate 17 thereby obtained in 25%
yield was subsequently hydrolyzed to furnish diol 6 in 23%
overall yield. Obviously, the low yield of di-p-nitrobenzo-
ate 17 was due to the steric hindrance present in both con-
formations of diol 5. Alternatively, via the route also uti-
lized in another laboratory,9 diol 5 was first subjected to a
NaI-promoted 1,4-elimination via its corresponding dime-
sylate to generate cyclohexadiene 18.6 Compound 18 was
then converted to diol 6 by adding singlet oxygen to the exo
face of cyclohexadiene 18 (using rose bengal as sensitizer)

Synthesis of Dihydropentacyclotetradecadiene
J. Chin. Chem. Soc., Vol. 55, No. 1, 2008 173
broad signal (d 4.51)6 displayed by the corresponding
a-hydrogens in diol 5 (Scheme III). The upfield shift ex-
hibited by the a-hydrogens is attributed to the consequence
of anisotropic shielding effect on the inward a-hydrogens
by the face-to-face juxtaposed dichlorinated double bond,16,17
a situation which occurs only in the “unfolded” boat-con-
formation 6a.
Scheme III
O
H3CO
H3CO
NO2
d 4.51
OH
H
Cl
O
Cl
H3CO
H3CO
p-nitrobenzoic acid
H
Cl
Cl
Cl
Cl
Cl
HO
O
Ph3P, DEAD, THF
reflux, 48 h
H
H
NO2
Cl
O
25%
17
5 (5b)
Expecting that the steric interaction between cis-ori-
ented groups of more bulky size would increase in the
“folded” conformation resembling 6b, we thought that the
conformational preference of dibenzoyloxy derivative 17
for the “unfolded” conformation similar to 6a would be en-
hanced, and accordingly the conformation-controlled p-fa-
cial selectivity in the Diels-Alder reaction of 17. As shown
in Scheme IV, di-p-nitrobenzoate 17 behaved like diol 6 to
undergo the Diels-Alder reaction with TDCp only at rather
harsh temperature (125-135 °C) as a neat mixture; how-
ever, the reaction surprisingly furnished the adduct of op-
posite configuration, the endo,anti,endo-adduct 19 in 65%
yield.18 The determination of the structure of adduct 19 was
supported by transformation to the corresponding diol 3b
(= 2b) via hydrolysis. Presumably, steric congestion in the
transition state of the reaction of TDCp and the “folded”
conformation of 17 was less severe than that of TDCp and
the “unfolded” conformation of 17, in which the existing
and developing dichlorinated double bonds flanked the two
bulky benzoyloxy groups.
NaOH, MeOH
rt, 2 h
ref. 6
91%
H3CO
H
H
H3CO
Cl
1. O2, rose bengal
acetone, 0
oC, hn
OH
Cl
H3CO
H3CO
-
5
Cl
Cl
Cl
Cl
H
HO
Cl
2. Zn, HOAc, rt, 2 h
83%
H
Cl
d 4.19
18
6 (6a)
TDCp
CaCO3
125 oC, 4 d
82%
OH
OCH3
H3CO
Cl
Cl
OCH3
H3CO
H
Cl
Cl
Cl
HO
H
Cl
Cl
Cl
3a
followed by reducing the resulting endoperoxide with zinc
dust in acetic acid a route of more work, but of higher re-
wards in terms of the overall yields.14 Diels-Alder reactions
of diol 6 with TDCp in the presence of CaCO3 constantly
furnished endo,syn,endo-diol 3a in yields of more than
80% without contamination with another stereoisomer
3b.8,15
Scheme IV
17
At the time we were successful in inverting the con-
figuration of hydroxy group-bearing carbon atoms in endo,
endo-diol 5 and established the structure of exo,exo-diol 6,7
Forman and Dailey reported the attainment of diol 6 via the
abovementioned second route and successfully carried out
the Diels-Alder reaction of diol 6 with TDCp to form
endo,syn,endo-diol 3a in their synthetic approach toward
hexaprismane and heptaprismane.9 The results from these
two laboratories supported our speculation of the confor-
mational preference and the conformation-controlled p-fa-
cial selectivity in the Diels-Alder reactions of diols 5 and 6
(Scheme I). The conformational preference of these two
TDCp
135 oC, 2 d
65%
O
O
NO2
O
Cl
Cl
Cl
Cl
O2N
H3CO
Cl
Cl
OH
H
H
O
HO
H
NaOH
H3CO
Cl
Cl
OCH3
OCH3
OCH3
MeOH
rt, 12 h
H3CO
H3CO
H
Cl
Cl
Cl
Cl
Cl
Cl
OCH3
Cl
Cl
3b (= 2b)
19
Endo,syn,endo-diol 3a was then subjected to reduc-
tive dechlorination (Na/tert-BuOH) in refluxing THF to af-
ford bis-acetal diol 209 in 85% yield (Scheme V). When
diketal diol 20 was treated with CuCl2·H2O in refluxing
acetonitrile for 2 h,19 the reaction provided a quantitative
yield of diketonic diol 21,9 which was subsequently sub-
jected to acetylation (Ac2O/Et3N) to furnish the diketonic
1
diols was also suggested by the difference in H NMR
chemical shifts displayed by the hydrogens at the hydroxy
group-bearing carbons. The a-hydrogens at carbons bear-
ing hydroxyl groups in diol 6 displayed a broad signal at d
4.19, which is at higher field by about 0.32 ppm than the

174 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Chou et al.
mass spectral and elemental analytical data, diketal diol 24
shows inverted configurations for carbons bearing hydrox-
yl groups (relative to those in 20) as indicated by the 1H
NMR spectrum in CDCl3. The a-hydrogens at carbons
bearing hydroxyl groups in diketal diol 24 display a broad
signal at d 4.18 (d 4.06 in acetone-d6), which is at lower
field by about 1.5 ppm than the multiplet (d 2.59-2.63
ppm)9 displayed by the corresponding a-hydrogens in
diketal diol 20. Again, the upfield shift exhibited by the
a-hydrogens in diketal diol 20 is attributed to the conse-
quence of anisotropic shielding effect on the inward a-hy-
drogens by the two face-to-face juxtaposed double bonds
across the cyclohexadiol ring and is well demonstrated in
other similar compounds reported16 and prepared in this
laboratory.17 A similar difference in chemical shifts exhib-
ited by these a-hydrogens in isomeric diketone diols 21
and 25 was also observed (Scheme V). Diketone diol 25
was obtained in 90% yield simply by hydrolysis of diketal
diol 24 in THF with 10% aqueous HCl. Attempt of bis-ace-
tylation of 25 (Ac2O/Et3N/4-DMAP) led only to the isola-
tion of mono-acetylated diketone 26 in 92% yield, without
a noticeable amount of diacetylated product 27, reflecting
the facts that hydroxyl groups are located inside the molec-
ular cavity of diol 25 and the epimerization of diol 20 to
diol 24 has been successfully implemented. The structures
and the inherent C2v symmetry for all synthetic intermedi-
ates were clearly revealed from spectral characteristics, ex-
cept acetate 26, which was shown to lose one of the two
symmetry elements present in its precursors (see the Exper-
imental Section).
Scheme V
diacetate 22 in 93% yield. The structure of 22 was sug-
gested by the elemental analysis in accordance with the
molecular formula C20H20O6 and supported by the spectral
1
data, in which a six-hydrogen singlet at d 2.08 in the H
NMR spectrum and a signal at d 169.8 in the 13C NMR
spectrum indicated the presence of two acetoxy groups.
The presence of ketonic functional groups in 22 were re-
vealed by a strong absorption band at 1779 cm-1 in the IR
spectrum and a signal at d 201.0 in the 13C NMR spectrum,
which are characteristics of a bicyclo[2.2.1]heptan-7-one
unit. The outward orientation of two acetoxy groups in
diacetate 22 is inherited from endo,syn,endo-diol 3a and is
maintained throughout its synthesis. For structural and
property comparison, we prepared the known diketal dione
239 by oxidation of diketal diol 22 using Jones reagent, and
anticipated that the metal-hydride reduction would occur at
the convex side (anti to the carbon-carbon double bond) of
dione 23 to deliver a diol having the two hydroxyl groups
placed inside the cavity and sandwiched by two double
bonds.
With diacetate 22 and 26 in hand, we started to inves-
tigate their thermal and photochemical behavior. As shown
in Scheme VI, when a solution of diacetate 22 in toluene
was sealed in a reaction tube with hydroquinone and heated
at 135 °C for 11 h, thermolysis occurred and an 86% yield
of the diacetate 28 was obtained. The ten-line 13C NMR
spectrum with two carbonyl carbons (d 208.1; d 170.4) and
one olefinic carbon (d 134.9) clearly established the forma-
tion of caged diacetate 28 from diacetate 22 via the course
of mono-decarbonylation followed by a rapid intramolecu-
lar Diels-Alder reaction. However, with maleic anhydride
present in the reaction mixture, low yield of caged diacetate
28 in company with yet unidentified complex products was
observed in numerous attempts. We did not observe any
product derived from intermolecular or domino Diels-Al-
der cycloaddition to yield the anticipated hexacyclic adduct
similar 10 (Scheme II).
Thus, as illustrated in Scheme V, reduction of dione
23 in THF with LiAlH4 gave diketal diol 24 in 91% yield.
Structurally isomeric to diketal diol 20, as indicated by the

Synthesis of Dihydropentacyclotetradecadiene
J. Chin. Chem. Soc., Vol. 55, No. 1, 2008 175
with those between diacetate 33 and its parent compound
34 (Dn 3.83 ppm).20 On the contrary, although mono-acety-
lated diketone 26 gave a comparable result to 22 upon
thermolysis, yielding caged monoacetate 32 in 70% yield
via the course of mono-decarbonylation followed by a
rapid intramolecular Diels-Alder reaction, 26 did not un-
dergo a symmetry-allowed [4+4] photocyclization under
the same conditions. The photochemical reaction was
found to give a complicated mixture of products from
which only the caged monoacetate 32 could be isolated in
50% yield (Scheme VI).
Scheme VI
H
OAc
OH
H
AcO
AcO
H
PhMe, hydroquinone
reflux, 2 days or
135 oC, seal tube, 11 h
d 4.72 (s)
O
O
70 %
86 %
28
22 26
32
22 26
(7%)
28
32 50%
hn (254 nm), PhH, 8-10 h
+
O
O
OH
HO
Jones
reagent
OAc
AcO
H
10% aq NaOH
MeOH, rt, 5 h
H
H
H
acetone
oC - rt,
3 h
d 4.51
(m)
(66%)
90%
0
16
30
29
65%
O
O
O
R'1
22: R1 = R'1 = OAc;
R2 = R'2 = H
26: R1 = R'1 = H;
OH
H
R'2
R1
R2
R2 = OAc, R'2 = OH
31
Hydrolysis of diacetoxy diene 29 with NaOH in
methanol gave the corresponding diol 30 in 90% yield.
Upon oxidation with Jones reagent in acetone, diol 30 un-
derwent a fast transannular reaction to afford bridged
hemiacetal 31 in 65% yield, without the desired dione 16
(Scheme V). Hemiacetal 31 showed high stability and
could not be opened to hydroxyl-ketone form by hydroly-
sis, resisted further oxidation to 16, and refused to go back
to diol 30 upon reduction with LiAlH4. The elemental anal-
ysis and spectral characteristics, particularly the broad ab-
sorption band at 3250 cm-1 in the IR spectrum and signals at
d 115.2 (s) and d 79.3 (d) in the 13C NMR spectrum, sup-
ported the structure of hemiacetal 31. The structure was
further analyzed and unambiguously established by sin-
gle-crystal X-ray crystallography (Fig. 1). Asuitable single
crystal of hemiacetal 31 was obtained by crystallization
from acetone-CH2Cl2 in orthorhombic space group Pbca.
Fig. 1A shows the ORTEP plots of molecular structures for
31. Analysis of the molecular structure reveals that the
overall geometry of 31 is, in general, comparable to that of
similar caged compounds.10a An elongated carbon-carbon
bond length of 1.6103 (17) Å for C3-C13 (C6-C10) is ob-
served. The dihedral angle for C3-C4-C5-C6 and C10-
C11-C12-C13 planes is 49.7°, resulting in a separation of
carbon-carbon double bond by a distance of 2.875 Å and an
interorbital angle of 130.3°. The major force to support
crystal packing is the intermolecular hydrogen bonding be-
tween hemiacetal moieties with an O···H distance of 1.85 Å
and an O-H···O angle of 168.5° (Fig. 1B).
On the other hand as shown in Scheme VI, irradiation
(l 254 nm, Rayonet) of a dilute solution of diacetate 22 in
benzene for 10 h furnished two products isolated by chro-
matography in 7% and 66% yields, respectively. The minor
product (28) was proved to be identical to the compound
obtained from the thermolysis of 22 by spectral and chro-
matographic comparison. The IR spectrum of the major
product did not show a norbornan-7-one type carbonyl ab-
sorption band. A six-line 13C NMR spectrum with one ole-
finic carbon (d 130.2) and one carboxyl carbon (d 171.1)
for a molecular formula C18H20O4, together with a 1H NMR
spectrum containing only five groups of chemically non-
equivalent hydrogens, clearly indicated the presence of C2v
symmetry in molecular structure. These spectral data also
suggested the skeleton of diacetyl diene 29, the major prod-
uct obtained from the photolysis of 22, was similar to that
of pentacyclic diene 9 (Scheme II), which resulted from the
occurrence of double decarbonylation with concomitant
[4+4] photocyclization. The stereochemistry of the two
acetoxy groups was maintained in the thermolysis and
photolysis of 22 leading to the formation of 28 and 29.
These acetoxy groups in 28 and 29 of occupy the endo posi-
tions, directing inward the boat-form cyclohexane ring, as
supported by the differences in chemical shifts (Dn) for the
geminal exo hydrogens between 28 (d 4.72) and 29 (d 4.51)
and their respective parent compounds 8 and 9 (28 vs. 8: Dn
3.45 ppm; 29 vs 9: Dn 3.66 ppm), which are comparable

176 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Chou et al.
tetrachloro-5,5-dimethoxycyclopentadiene (TDCp) with
stereoisomeric 5,6,7,8-tetrachloro-1,4,4a,5,8,8a-hexahy-
dro-9,9-dimethoxy-5,8-methanonaphthalene-1,4-diols, 5
and 6. Endo,endo-diol 5 and exo,exo-diol 6 appeared to
have different conformational preferences determined by
the configurations of carbon atoms bearing hydroxy groups,
and thus afforded endo,anti,endo-adduct 2b and endo,
syn,endo-adduct 3a, respectively (Scheme I). Two routes
were employed to achieve the configurational inversion of
hydroxy-bearing carbon atoms in diol 5, which involved
directly Mitsunobu protocol and in a roundabout way via
the endoperoxide of cyclohexadiene 13 prepared from diol
5 (Scheme III). The thermolysis of diacetate 22 produced
endo,endo-3,6-diacetoxyhexacyclo[6.6.1.02,7.04,13.05,10.09,14]-
pentadeca-11-en-15-one (28), resulting from decarbonyl-
ation with successive occurrences of a [4+2] intramolecu-
lar Diels-Alder reaction. The photolysis of diacetate 22 was
found to produce, in addition to enone 28, endo,endo-2.9-
diacetoxypentacyclo[8.4.0.03,8.04,14.07,11]tetradeca-5,12-
diene (29), resulting from decarbonylation with successive
occurrences of a symmetry-allowed [4+4] photocycliza-
tion (Scheme VI). Synthesis of 27, the stereoisomer of
dione 22, having two acetoxy groups located inside the
cavity between the two etheno-bridge double bonds was
not successful. Only the corresponding monoacetate 26
was obtained, which upon thermolysis and photolysis gave
only hexacyclic enone 32. Pentacyclic diacetate 29 was
converted by hydrolysis to the title diendiol 30, which upon
oxidation afforded stable hexacyclic bridged hemiacetal 31
as a result of facile transannular reaction and accordingly
precluded our pursuit of tetraene 14 via diketonic precursor
16 (Scheme VI). The structure of hemiacetal 26 was ana-
lyzed by single-crystal X-ray crystallography.
(A)
EXPERIMENTAL SECTION
(B)
General
Fig. 1. (A) The ORTEP drawing for molecular struc-
ture of 31 and (B) part of crystal structure of 31,
showing the formation of hydrogen-bonded ar-
ray (yellow dashed lines, d = 1.85 Å; angle
168.5°).
Melting points were determined in capillaries on a
Thomas-Hoover or Büchi Melting Point B-540 apparatus
and are uncorrected. Infrared (IR) spectra were recorded on
a JASCO 400-plus or Perkin-Elmer 682 spectrophotometer
as a solid suspended in a KBr disk. 1H and 13C NMR spectra
were collected on a Brüker DPX-400 or Varian Unity-300
spectrometer using CDCl3 as solvent (unless otherwise
specified). Coupling constants are reported in hertz. The
number of attached hydrogens on the carbon atom was de-
termined by DEPT analysis. The assignment of proton and
CONCLUSION
We have demonstrated the conformation-controlled
p-facial selectivity in the Diels-Alder reactions of 1,2,3,4-

Synthesis of Dihydropentacyclotetradecadiene
J. Chin. Chem. Soc., Vol. 55, No. 1, 2008 177
1
carbon NMR peaks was supported by H-1H COSY and
IR (KBr) 2955 (m), 1740 (s), 1617 (m), 1536 (s), 1278 (s),
1
HMQC spectra and for some compounds in addition by
NOESY spectra. Mass (MS) spectra were obtained on a VG
Trio-2000 GC/MS or TRIO-2000 GC-MS instrument by
the EI mode unless otherwise indicated. All solvents used
were either reagent grade or were distilled prior to use. An-
alytical thin-layer chromatography (TLC) was performed
on E. Merck silica gel 60 F254 plate (0.20 mm). Flash chro-
matography was performed on E. Merck silica gel (230-
400 mesh). Microanalyses were performed by the NSC An-
alytical Centers operated by Cheng Kung University, Tai-
nan, or Chung Hsing University, Taichung, Taiwan.
750 cm-1 (s); H NMR (300 MHz, CDCl3) d 8.21-8.28
(AA’BB’ pattern, 8H), 6.04 (d, J = 1.5 Hz, 2H), 5.55-5.56
(m, 2H), 3.71 (s, 3H), 3.59 (s, 3H), 3.42 (d, J = 3.6 Hz, 2H);
13C NMR (75.4 MHz, CDCl3) d 163.6 (s), 150.8 (s), 135.1
(s), 130.9 (d), 130.1 (d), 129.8 (s), 123.6 (d), 111.7 (s), ~ 77
(s, hidden, C–Cl), 67.1 (d), 53.1 (q), 52.1 (q), 49.4 (d); MS
(EI, 70 eV) m/z (relative intensity) 672 (M+, 3), 637 (92),
472 (35), 303 (100), 257 (35), 194 (15), 150 (97), 104 (48).
Anal. Calcd for C27H20Cl4N2O10: C, 48.10; H, 2.99; Cl,
21.03; N, 4.15. Found: C, 48.32; H, 3.25; Cl, 21.03; N,
4.01.
(la,4a,4ab,5b,8b,8aa,9b,9ab,10b,10aa)-1,2,3,4,5,6,7,8-
octachloro-1,4,4a,5,8,8a,9,9a,10,10a-decahydro-
11,11,12,12-tetramethoxy-[1,4;5,8]dimethanoanthra-
cene-9,10-diol (2b)
(lb,4b,4ab,5a,8a,8ab)-5,6,7,8-tetrachloro-1,4,4a,5,8,8a-
hexahydro-9,9-dimethoxy-5,8-methanonaphthalene-
1,4-diol (6)
Into a stirring solution of bis-p-nitrobenzoate 17 (1.0
g, 1.5 mmol) in acetone (5 mL) was added dropwise a
MeOH solution (10 mL) of NaOH (0.2 g, 5 mmol). After
stirring for 2 h, solvents were removed under reduced pres-
sure to give a gray solid residue, which was mixed with wa-
ter (20 mL), and extracted with CH2Cl2 (15 mL ´ 2). The
combined organic layers were washed successively with
saturated sodium carbonate solution (10 mL), water (20
mL), and brine (20 mL), and then dried (MgSO4) and fil-
tered. Removal of solvent under reduced pressure gave
solid residue, which was recrystallized from EtOAc/nHex
to afford diol 6 (0.5 g, 91%) as colorless crystals: mp
147-148 °C; IR (KBr) 3280 (br s), 2949 (m), 1660 (m),
1448 (w), 1277 cm-1 (m); 1H NMR (300 MHz, CDCl3) d
5.95 (d, J = 2.1 Hz, 2H), 4.19 (br, 2H), 3.64 (s, 3H), 3.56 (s,
3H), 3.08 (m, 2H), 2.51 (br, 2H, -OH); 13C NMR (75.4
MHz, CDCl3) d 132.1 (d), 129.1 (s), 111.9 (s), ~ 77 (s, hid-
den, C–Cl), 63.6 (d), 53.0 (d), 52.8 (q), 51.8 (q); MS (EI, 70
eV) m/z (relative intensity) 339 (M+– Cl – H , 35), 303 (5),
253 (100), 223 (5), 207 (30). Anal. Calcd for C13H14Cl4O4:
C, 41.52; H, 3.75; Cl, 37.71. Found: C, 41.42; H, 3.74; Cl,
37.92.
A solution of enediol 56 (1.0 g, 2.7 mmol) and TDCp
(0.7 g, 2.7 mmol) in xylene (15 mL) was heated under re-
flux for 2 days. The resulting white precipitates were col-
lected and recrystallized from acetone to afford adduct 2b
(1.5 g, 85%): mp 270-271 °C; IR (KBr) 3273 (br s), 2857
1
(m), 1610 (m), 1464 (m), 1188 cm-1 (s); H NMR (300
MHz, acetone-d6) d 4.90 (d, J = 8.4 Hz, 2H, -OH), 4.27 (d, J
= 8.4 Hz, 2H), 3.58 (s, 3H), 3.54 (s, 3H), 3.47 (s, 3H), 3.45
(s, 3H), 3.15 (br, 2H), 2.52 (br, 2H); 13C NMR (75.4 MHz,
acetone-d6) d 130.32 (s), 130.31 (s), 115.78 (s), 115.68 (s),
78.1 (s), 77.4 (s), 61.7 (d), 53.7 (d), 53.3 (q), 53.0 (q), 52.3
(q), 52.1 (q), 49.7 (d); MS (EI, 70 eV) m/z (relative inten-
sity) 636 (M+, 4), 601 (55), 573 (67), 253 (100), 207 (30).
Anal. Calcd for C20H20Cl8O6: C, 37.53; H, 3.15; Cl, 44.32.
Found: C, 37.48; H, 3.13; Cl, 44.35.
(lb,4b,4ab,5a,8a,8ab)-5,6,7,8-Tetrachloro-1,4,4a,5,8,8a-
hexahydro-9,9-dimethoxy-5,8-methanonaphthalene-
1,4-diol Di-p-nitrobenzoate (17)
Diethyl azodicarboxylate (0.9 g, 5.3 mmol) was
added dropwise into a stirring THF solution (30 mL) con-
taining enediol 56 (1.0 g, 2.7 mmol), triphenylphosphine
(1.4 g, 5.3 mmol), and p-nitrobenzoic acid (0.9 g, 5.4
mmol). After the addition was completed, the reaction mix-
ture was heated under reflux for 2 days. Removal of solvent
left a brown viscous residue, into which methanol (50 mL)
was added, and the resultant solution was set aside over-
night. The precipitates thereby formed were collected and
recrystallized from EtOAc/nHex to give bis-p-nitrobenzo-
ate 17 (0.44 g, 25%) as a white crystalline: mp 230-231 °C;
(la,4a,4ab,5a,8a,8ab,9b,9ab,10b,10ab)-1,2,3,4,5,6,7,8-
Octachloro-1,4,4a,5,8,8a,9,9a,10,10a-decahydro-
11,11,12,12-tetramethoxy-[1,4;5,8]dimethanoanthra-
cene-9,10-diol (3a)9
A mixture of enediol 6 (1 mmol) and TDCp (1.05
mmol) was heated at 125 °C for 2 days in the presence of a
catalytic amount of CaCO3. After the reaction mixture was
cooled to room temperature, the reaction mixture was dis-

178 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Chou et al.
solved in hot ethanol and decolorized with activated char-
coal and filtered through a pad of Celite. The filtrate was
concentrated under reduced pressure to give crude product,
which was recrystallized from dichloromethane to afford
pure 3a (82-86%): mp 206-207 °C; IR (KBr) 3515 (br, m),
2954 (m), 1604 (m), 1278 (m), 1192 cm-1 (s); 1H NMR (300
MHz, CDCl3) d 3.60 (s, 3H), 3.56 (s, 3H), 3.27-3.38 (m,
20.4 mmol). The mixture was heated under reflux and the
progress of the reaction was monitored by TLC (EtOAc/
nHex 4:1). When the reaction was complete (2 h), the reac-
tion mixture was cooled to room temperature, and the sol-
vent was removed under reduced pressure to give a brown
solid residue, which was purified by flash chromatography
on a silica gel column (EtOAc/nHex 4:1; Rf = 0.60) and
recrystallized from EtOAc to furnish diol diketone 21 (2.72
g, 98%) as white powder: mp 175-176 °C; IR (KBr) 3593
(s), 3243 (br), 2930 (m), 1774 (s), 1664 (m), 1374 (m),
1337 (m), 1056 (s), 720 cm-1 (m); 1H NMR (400 MHz, ace-
tone-d6) d 6.55 (dd, J = 2.3, 2.3 Hz, 4H), 4.14 (d, J = 5.6 Hz,
2H), 3.03-3.01 (m, 4H), 2.86-2.84 (m, 2H), 2.39-2.35 (m,
4H); 13C NMR (100 MHz, acetone-d6) d 204.4 (s), 133.6
(d), 68.0 (d), 51.4 (d), 44.1 (d); MS (EI, 70 eV) m/z (rela-
tive intensity) 272 (M+, 7), 244 (M+-28, 21), 226 (11), 208
(15), 145 (32), 128 (27), 115 (36), 107 (64), 91 (100). Anal.
Calcd for C16H16O4: C, 70.57; H, 5.92. Found: C, 70.66; H,
6.07.
2H), 2.82-2.85 (m, 4H), 2.36 (d, J = 2.7 Hz, 2H, -OH); 13
C
NMR (75.4 MHz, CDCl3) d 129.5 (s), 111.0 (s), ~ 77 (s,
hidden, C–Cl), 66.6 (d), 52.7 (q), 51.9 (q), 51.9 (d); MS
(EI, 70 eV) m/z (relative intensity) 636 (M+, 1), 603 (100),
253 (11), 207 (10).
(la,4a,4ab,5b,8b,8aa,9b,9ab,10b,10aa)-1,2,3,4,5,6,7,8-
octachloro-1,4,4a,5,8,8a,9,9a,10,10a-decahydro-
11,11,12,12-tetramethoxy-[1,4;5,8]dimethanoanthra-
cene-9,10-diol Di-p-nitrobenzoate (19)
A mixture of bis-p-nitrobenzoate 17 (0.1 g, 0.15
mmol) and TDCp (2 mL) was heated at 130 °C for 2 days.
After the reaction mixture was cooled to room temperature,
the reaction mixture was chromatographed on a silica gel
column (EtOAc/nHex 1:5) and recrystallized from EtOAc
to furnish pure adduct 19 (0.09 g, 65%): mp 279-280 °C; IR
(KBr) 1737 (s), 1600 (m), 1530 (s), 1261 (s), 1194 cm-1
(m); 1H NMR (300 MHz, acetone-d6) d 8.40 (AA’BB’ pat-
tern, 8H), 5.39-5.44 (m, 2H), 3.85 (br, 2H), 3.72 (s, 3H),
3.54 (s, 3H), 3.53 (s, 3H), 3.50 (d, J = 3 Hz, 2H), 3.47 (s,
3H); 13C NMR (75.4 MHz, acetone-d6) d 162.9 (s), 151.0
(s), 134.9 (s), 131.3 (d), 130.3 (s), 123.8 (d), 115.6 (s),
116.9 (s), 77.4 (s), 76.3 (s), 68.7 (d), 52.4 (q), 52.1 (q), 51.7
(q), 51.6 (q), 47.5 (d), 46.2 (d); MS (EI, 70 eV) m/z (rela-
tive intensity) 940 (M+, 1), 903 (100), 901 (90), 865 (40),
770 (52), 736 (30), 605 (35). Anal. Calcd for C34H26Cl8N2O12:
C, 43.53; H, 2.79; Cl, 30.23; N, 2.99. Found: C, 43.76; H,
3.03; Cl, 30.2; N, 3.00.
(la,4a,4ab,5a,8a,8ab,9b,9ab,10b,10ab)-
1,4,4a,5,8,8a,9,9a,10,10a-Decahydro-11,12-dioxo-
[1,4;5,8]dimethanoanthracene-9,10-diol Diacetate (22)
A mixture of diketonic diol 21 (0.153 g, 0.53 mmol),
Et3N (0.8 mL, 5.74 mmol), and acetic anhydride (0.8 mL,
8.5 mmol) was stirred at room temperature under a nitrogen
atmosphere for 3.5 h (monitored by TLC). The reaction
mixture was then cooled with an ice bath and ice-cold water
was then added (20 mL), and extracted with dichloro-
methane (10 mL ´ 3). The combined extracts were washed
in sequence with saturated aqueous NaHCO3 (20 mL), wa-
ter (20 mL), and brine, then dried (MgSO4) and filtered.
The solvent was removed under reduced pressure to give a
pale yellow solid residue, which was purified by recrys-
tallization from CH2Cl2/Ether (1:1) to afford diacetate 22
(0.186 g, 93%) as colorless flakes: mp 178-179 °C; IR
(KBr) 2958 (w), 2921 (w), 1779 (s), 1747 (s), 1659 (w),
Bis-p-nitrobenzoate adduct 19 was hydrolyzed by
stirring in methanol with NaOH for 12 h to give diol adduct
3b in quantitative yield (95%), which was analyzed to be
identical to the adduct 2b obtained from the Diels-Alder re-
action of TDCp with enediol 5.
1
1236 (s), 1033 (s), 729 cm-1 (s); H NMR (400 MHz,
CDCl3) d 6.53 (dd, J = 2.3, 2.3 Hz, 4H), 4.30-4.25 (m, 2H),
2.85-2.83 (m, 4H), 2.59-2.56 (m, 4H), 2.08 (s, 6H); 13C
NMR (100 MHz, CDCl3) d 201.0 (s), 169.8 (s), 132.5 (d),
69.1 (d), 49.3 (d), 40.0 (d), 20.9 (q); MS (EI, 70 eV) m/z
(relative intensity) 357 (M++1, w), 328 (M+-28, 10), 268
(16), 240 (13), 226 (16), 209 (18), 208 (100), 179 (57), 165
(32), 128 (87), 115 (21), 107 (64), 91 (93), 77 (27). Anal.
Calcd for C20H20O6: C, 67.40; H, 5.65. Found: C, 67.15; H,
(la,4a,4ab,5a,8a,8ab,9b,9ab,10b,10ab)-
1,4,4a,5,8,8a,9,9a,10,10a-Decahydro-11,12-dioxo-
[1,4;5,8]dimethanoanthracene-9,10-diol (21)
To a solution of diol bis-acetal 209 (3.72 g, 10.2
mmol) in MeCN (50 mL) was added CuCl2·2H2O (3.48 g,

Synthesis of Dihydropentacyclotetradecadiene
5.62.
J. Chin. Chem. Soc., Vol. 55, No. 1, 2008 179
3180 (br), 2894 (m), 1767 (s), 1492 (m), 1119 (m), 1092
(m), 1017 (m), 836 cm-1 (w); 1H NMR (400 MHz, CDCl3) d
6.45 (dd, J = 2.4, 2.4 Hz, 4H), 4.36 (d, J = 7.9 Hz, 2H), 3.06
(br, 4H), 2.59 (br, 4H), 2.53 (d, J = 7.9 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 199.0 (s), 129.9 (d), 67.4 (d), 50.4 (d),
42.2 (d); MS (EI, 70 eV) m/z (relative intensity) 272 (M+,
4), 244 (M+- 28, 63), 165 (42), 130 (50), 107 (55), 90 (42),
78 (46), 77 (100). Anal. Calcd for C16H16O4: C, 70.57; H,
5.92. Found: C, 70.66; H, 5.96.
(la,4a,4ab,5a,8a,8ab,9a,9ab,10a,10ab)-
1,4,4a,5,8,8a,9,9a,10,10a-Decahydro-11,11,12,12-
tetramethoxy-[1,4;5,8]dimethanoanthracene-9,10-diol
(24)
Into a stirring solution of bis-acetal dione 239 (3.34 g,
9.34 mmol) in dried THF (50 mL) under N2 atmosphere at 0
°C was added LiAlH4 (1.75 g, 46.1 mmol) in portions. The
reaction mixture was then allowed to warm up to room tem-
perature and gently heated at refluxing temperature for 7 h.
After the reaction mixture was cooled down to 0 °C, ice-
cold water (2 mL) was carefully added followed by addi-
tion of 10% HCl solution (20 mL), and then extracted with
dichloromethane (100 mL ´ 3). The combined extracts
were washed sequentially with saturated aqueous NaHCO3
(50 mL), water (50 mL), and brine, then dried (MgSO4) and
filtered. The solvent was removed under reduced pressure
to give a pale yellow solid residue. Recrystallization of sol-
ids from acetone afforded bis-acetal diol 24 (3.07 g, 91%)
as white prisms: mp 196-197 °C; IR (KBr) 3464 (s), 3280
(br), 3079 (m), 2967 (s), 2898 (s), 2829 (m), 1469 (m),
1269 (s), 1100 (s), 1066(s), 709 cm-1 (m); 1H NMR (400
MHz, acetone-d6) d 5.87 (dd, J = 2.0, 2.0 Hz, 4H), 4.06 (br,
2H), 3.43 (d, J = 8.3 Hz, 2H), 3.14 (s, 6H), 3.01 (s, 6H),
2.73 (br, 4H), 2.45 (br, 4H); 13C NMR (100 MHz, acetone-
d6) d 131.6 (d), 119.8 (s), 68.3 (d), 51.8 (q), 49.7 (q), 48.8
(d), 46.1 (d); MS (EI, 70 eV) m/z (relative intensity) 364
(M+, 27), 349 (M+- Me, 7), 333 (M+- OMe, 9), 151 (100),
91 (32), 58 (40). Anal. Calcd for C20H28O6: C, 65.91; H,
7.74. Found: C, 65.80; H, 7.75.
(la,4a,4ab,5a,8a,8ab,9a,9ab,10a,10ab)-
1,4,4a,5,8,8a,9,9a,10,10a-Decahydro-11,12-dioxo-
10-hydroxy-[1,4;5,8]dimethanoanthracene-9-ol Acetate
(26)
A mixture of dihydroxy dione 25 (304 mg, 1.12
mmol), triethylamine (2.8 mL, 20.1 mmol), acetic anhy-
dride (3.2 mL, 33.4 mmol), and a catalytic amount of 4-
DMAP (10 mg) was stirred at room temperature under a N2
atmosphere for 7 h. The resultant mixture was cooled to 0
°C with an ice-water bath, ice-water (20 mL) was added,
and then extracted with CH2Cl2 (10 mL ´ 3). The combined
organic layers were washed sequentially with saturated so-
dium carbonate solution (20 mL), water (20 mL), and brine
(20 mL). The solution was dried (MgSO4), filtered, and
concentrated to leave a yellow residue, which was recrys-
tallized from CH2Cl2 to afford monoacetate 26 (322 mg,
92%) as colorless crystalline: mp 146-147 °C (decomp.);
IR (KBr) 3526 (s), 2917 (m), 1769 (s), 1745 (s), 1223 (s),
1199 (s), 693 cm-1 (s); 1H NMR (400 MHz, CDCl3) d 6.58
(dd, J = 6.4, 3.8 Hz, 2H), 6.10 (dd, J = 6.5, 3.6 Hz, 2H),
5.72 (t, J = 3.9 Hz, 1H), 4.26 (dt, J = 13.2, 4.1 Hz, 1H), 3.10
(dd, J = 3.2, 3.2 Hz, 2H), 2.99 (dd, J = 3.1, 3.1 Hz, 2H),
2.69 (ddd, J = 11.8, 3.7, 3.7 Hz, 2H), 2.61 (ddd, J = 11.8,
3.8, 3.8 Hz, 2H), 2.18 (d, J = 13.2 Hz, 1H), 2.04 (s, 3H); 13C
NMR (100 MHz, CDCl3) d 198.1 (s), 168.6 (s), 132.5 (d),
127.5 (d), 67.0 (d), 66.9 (d), 50.5 (d), 49.7 (d), 41.7 (d),
40.2 (d), 22.1 (q); MS (EI, 70 eV) m/z (relative intensity)
314 (M+, w), 286 (M+- 28, 1), 198 (14), 120 (19), 91 (100),
79 (54), 77 (38). Anal. Calcd for C18H18O5: C, 68.77; H,
5.77. Found: C, 68.85; H, 6.02.
(la,4a,4ab,5a,8a,8ab,9a,9ab,10a,10ab)-
1,4,4a,5,8,8a,9,9a,10,10a-Decahydro-11,12-dioxo-
[1,4;5,8]dimethanoanthracene-9,10-diol (25)
To a stirring solution of bis-acetal diol 24 (1.36 g,
3.74 mmol) in THF (20 mL) cooled at 0 °C was added
dropwise 10% HCl solution (2 mL). After stirring at room
temperature (monitored by TLC) for another 14 h, the reac-
tion mixture was then extracted with dichloromethane (50
mL ´ 3). The combined extracts were washed successively
with saturated aqueous NaHCO3 (30 mL), water (50 mL),
and brine, then dried (MgSO4), filtered, and concentrated
under reduced pressure. The resulting pale yellow residue
was recrystallized from acetone to give dihydroxy dione 25
(0.92 g, 90%) as white powder: mp 131-133 °C; IR (KBr)
General procedure for photolysis of diketones 22 and
26
A solution of diketonic compound (0.5 mmol) in ben-
zene (200 mL, concentration ~ 2 mM) was stirred and irra-
diated with UV-light in a Rayonet apparatus (l 254 nm) for
8-10 h. (monitored by TLC). The solvent was then removed

180 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Chou et al.
under reduced pressure, and the resultant solid residue was
analyzed for the presence and ratio of the products by 1H
NMR. Chromatography on a silica gel column (EtOAc/
nHex 1:2 or 1:4) was followed by recrystallization to afford
pure product(s). Photolysis of diketones 22 for 10 h fur-
nished hexacyclic ketone 28 and pentacyclic diene 29 in
7% and 66% yields, respectively. Photolysis of diketones
26 for 8 h afforded hexacyclic ketone 32 as sole tractable
product in 50% yield.
6.34; Found: C, 71.23; H, 6.66.
General procedure for thermolysis of diketones 22
and 26
A solution of diketonic compound (1 mmol) and a
small amount of hydroquinone in toluene (10 mL) in the
absence or presence of maleic anhydride (1 – 5 mmol) was
sealed in a pressure tube and heated to 135 °C or was stirred
and heated under reflux for 2 days. The reaction mixture
was cooled to room temperature and concentrated under re-
duced pressure to leave a solid residue, which was analyzed
by 1H NMR and purified by recrystalization from EA/Hex-
ane to afford pure hexacyclic enone 28 (86%) from 22 and
32 (70%) from 26.
endo,endo-3,6-Diacetoxyhexacyclo[6.6.1.02,7.04,13.05,10.09,14
]
-pentadeca-11-en-15-one (28)
Mp 170-172 °C; IR (KBr) 2921 (m), 1779 (s), 1728
(s), 1659 (w), 1254 (s), 1038 cm-1 (s); 1H NMR (400 MHz,
CDCl3) d 6.40 (dd, J = 4.7, 3.1 Hz, 2H), 4.72 (s, 2H),
2.66-2.63 (m, 2H), 2.53 (br, 2H), 2.19-2.17 (m, 2H), 2.05
(s, 6H), 1.96 (br, 2H),1.82 (br, 2H); 13C NMR (100 MHz,
CDCl3) d 208.1 (s), 170.4 (s), 134.9 (d), 72.6 (d), 46.0 (d),
37.3 (d), 33.6 (d), 30.7 (d), 30.1 (d), 21.5 (q); MS (EI, 70
eV) m/z (relative intensity) 328 (M+, 34), 268 (17), 208
(100), 198 (18), 179 (50), 165 (21), 128 (61), 107 (38), 91
(62), 79 (29), 69 (42). Anal. Calcd for C19H20O5: C, 69.50;
H, 6.14. Found: C, 69.83; H, 5.89.
Transformation of pentacyclic diene 29 to bridged
hemiacetal 31
endo,endo-2.9-Dihydroxypentacyclo[8.4.0.03,8.04,14.07,11]-
etradeca-5,12-diene (30)
Into a stirring solution of pentacyclic diacetate 29
(0.51 g, 1.71 mmol) in MeOH (20 mL) cooled with an
ice-water bath was added dropwise a 10% aqueous NaOH
solution (5 mL). The resultant solution was stirred at room
temperature for 5 h, cooled to 0 °C, and neutralized with
10% aqueous HCl solution. The reaction mixture was ex-
tracted with CH2Cl2 (10 mL ´ 3), and the combined organic
layers were washed successively with saturated sodium
carbonate solution (20 mL), water (20 mL), and brine (20
mL). The solution was then dried (MgSO4), filtered, and
concentrated to leave a pale yellow viscous residue, which
was recrystallized from CH2Cl2/MeOH to afford diol 30
(0.33 g, 90%) as white powder: mp 224-226 °C (decomp.);
IR (KBr) 3174 (br), 2942 (m), 1270 (m), 1252 (m), 1114
(s), 808 (m), 680 cm-1 (m); 1H NMR (400 MHz, CDCl3) d
5.84 (dd, J = 5.4, 3.0 Hz, 4H), 3.74-3.71 (m, 2H), 2.74 (br,
4H), 2.23-2.21 (m, 4H), 1.63 (br, 2H);13C NMR (100 MHz,
CDCl3) d 130.4 (d), 71.9 (d), 42.5 (d), 41.7 (d); MS (EI, 70
eV) m/z (relative intensity) 216 (M+, 2), 198 (M+ -18, 17),
129 (12), 107 (20), 91 (100), 84 (61). Anal. Calcd for
C14H16O2: C, 77.75; H, 7.46. Found: C, 77.38; H, 7.59.
endo,endo-2.9-Diacetoxypentacyclo[8.4.0.03,8.04,14.07,11]-
tetradeca-5,12-diene (29)
Mp 139-140 °C; IR (KBr) 2965 (m), 1723 (s), 1651
(w), 1242 (s), 1083 (s), 815 cm-1 (m); 1H NMR (400 MHz,
CDCl3) d 5.87 (dd, J = 5.3, 3.0 Hz, 4H), 4.53-4.49 (m, 2H),
2.82 (br, 4H), 2.36 (br, 4H), 2.12 (s, 6H); 13C NMR (100
MHz, CDCl3) d 171.1 (s), 130.2 (d), 71.7 (d), 42.3 (d), 39.0
(d), 21.8 (q); MS (EI, 70 eV) m/z (relative intensity) 300
(M+, 4), 284 (17), 240 (17), 214 (20), 180 (56), 179 (100),
178 (41), 165 (22), 91 (20). Anal. Calcd for C18H20O4: C,
71.98; H, 6.71. Found: C, 71.79; H, 6.80.
exo-3-Acetoxy-exo-6-hydroxyhexacyclo-
[6.6.1.02,7.04,13.05,10.09,14]pentadeca-11-en-15-one (32)
Mp 179-182 °C; 1H NMR (400 MHz, CDCl3) d 6.41-
6.46 (m, 2H), 5.41-5.44 (t, 1H), 4.53-4.55 (t, 1H), 2.96 (d, J
= 3.4, 1H), 2.78 (d, J = 3.36, 1H), 2.52-2.54 (m, 2H), 2.29
(d, J = 3.36, 1H), 2.18 (d, J = 3.44, 1H), 2.07 (s, 3H), 1.97
(s, 1H), 1.96 (s, 1H), 1.92 (s, 2H); 13C NMR (100 MHz,
CDCl3) d 210.95 (s), 170.48 (s), 135.42 (d), 134.86 (d),
68.58 (d), 64.84 (d), 42.26 (d), 41.62 (d), 36.56 (d), 33.64
(d), 33.46 (d), 30.60 (d), 29.94 (d), 29.90 (d), 28.02 (d),
26.80 (d), 21.20 (q). Anal. Calcd for C17H18O4: C, 71.31; H,
15-Oxa-hexacyclo[6.6.1.02,7.03,13.06,10.09,14]pentadeca-
4,11-dien-1-ol (31)
Into a stirring solution of pentacyclic diol 30 (0.30 g,
1.41 mmol) in acetone (20 mL) cooled with an ice-water
bath was added dropwise Jones reagent (2 mL). The result-
ing solution was stirred at room temperature for 3 h, fol-

Synthesis of Dihydropentacyclotetradecadiene
J. Chin. Chem. Soc., Vol. 55, No. 1, 2008 181
lowed by addition of isopropanol (2 mL) and an excess
amount of NaHCO3. After stirring for an additional 2 h, the
reaction mixture was filtered through a pad of celite, and
the filtrate was extracted with CH2Cl2 (20 mL ´ 3). The
combined organic layers were washed successively with
saturated sodium carbonate solution (10 mL), water (10
mL), and brine (10 mL), then dried (MgSO4), filtered, and
concentrated to leave a pale yellow viscous residue. Re-
crystallizing the residue from CH2Cl2 afforded hemiacetal
31 (0.19 g, 65%) as colorless flakes: mp 218-220 °C
(decomp.); IR (KBr) 3254 (s), 2955 (m), 1632 (w), 1350
were refined anisotropically. Hydrogen atoms were placed
in calculated idealized positions. The residual peak and
hole of electron densities were 0.339 and -0.508 e Å-3, re-
spectively. The final R indices [(I>2s(I))]: R(F) = 0.0628,
wR(F 2) = 0.1531; GOF = 1.059 (for 202 parameters).
ACKNOWLEDGMENT
This work was supported by a grant from the National
Science Council of Taiwan.
1
(m), 1335 (m), 1050 (m), 695 cm-1 (m); H NMR (400
Received May 7, 2007.
MHz, CDCl3) d 5.95-5.87 (m, 4H), 4.51 (t, J = 4.8 Hz, 1H),
4.03 (br, 1H), 3.25-3.13 (m, 2H), 2.98-2.85 (m, 2H), 2.52-
2.44 (m, 2H), 2.02 (ddd, J = 10.3, 3.3, 2.6 Hz, 2H); 13C
NMR (100 MHz, CDCl3) d 131.6 (d), 131.0 (d), 115.2 (s),
79.3 (d), 49.2 (d), 47.8 (d), 43.4 (d), 42.9 (d); MS (EI, 70
eV) m/z (relative intensity) 214 (M+, 16), 169 (11), 141
(15), 116 (10), 91 (100), 77 (27). Anal. Calcd for C14H14O2:
C, 78.48; H, 6.58. Found: C, 78.13; H, 6.51.
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