A convenient road to 1-chloropentacycloundecanes - A joint experimental and computational investigation

Article abstract of DOI:10.1002/ejoc.201001731

An efficient synthetic strategy to obtain 1-chloro-C_s- trishomocubane and 1-chloro-D₃-trishomocubane is described. 1-Chloro-C_s-trishomocubane is synthesized by a regioselective Diels-Alder reaction, and B3PW91/6-31G(d,p) calculations offer a plausible explanation of the reaction mechanism. Surprisingly, 1-chloro-C _s-trishomocubane does not undergo an acid-catalyzed rearrangement to form 1-chloro-D₃-trishomocubane and was obtained by chlorosulfation of Cookson's diketone. A possible mechanism of the reaction involving the formation of C_s- and D₃-trishomocubane nonclassical cations was proposed on the basis of a mechanistic [B3PW91/6-31G(d,p) and MP2/cc-pVDZ] study. An efficient method to prepare 1-substituted pentacycloundecanes is described. Simple modification of the starting material for the Diels-Alder reaction gives 1-C_s-trishomocubane derivatives readily. Chlorosulfation of Cookson's diketone in four steps gives 1-chloro-D₃-trishomocubane in good yields. The proposed mechanism of the reactions is explained by DFT and MP2 calculations. Copyright

Full text of DOI:10.1002/ejoc.201001731

FULL PAPER
DOI: 10.1002/ejoc.201001731
A Convenient Road to 1-Chloropentacycloundecanes – A Joint Experimental
and Computational Investigation
[a]
[a]
[a]
[a]
Dmitry I. Sharapa, Alexander V. Gayday, Alena G. Mitlenko, Igor A. Levandovskiy,*
and Tatyana E. Shubina*[
b]
Keywords: Polycycles / Cage compounds / Reaction mechanisms / Density functional calculations / Ab initio calculations
An efficient synthetic strategy to obtain 1-chloro-C
homocubane and 1-chloro-D -trishomocubane is described.
-Chloro-C -trishomocubane is synthesized by a regioselec- son’s diketone. A possible mechanism of the reaction involv-
s
-tris-
an acid-catalyzed rearrangement to form 1-chloro-D
3
-tris-
3
homocubane and was obtained by chlorosulfation of Cook-
1
s
tive Diels–Alder reaction, and B3PW91/6-31G(d,p) calcula-
tions offer a plausible explanation of the reaction mechanism.
Surprisingly, 1-chloro-C -trishomocubane does not undergo
s
s 3
ing the formation of C - and D -trishomocubane nonclassical
cations was proposed on the basis of a mechanistic [B3PW91/
6-31G(d,p) and MP2/cc-pVDZ] study.
stable oils.[21,22] Also under active investigation is possibility
to use polymantanes in the nanoworld.
In general, the bioactivity profile of polycyclic cage com-
pounds can be effectively manipulated by means of struc-
tural modification, either within the polycyclic cage moiety
or by sidechain substitution. It was recently suggested that,
Introduction
[
23]
Polycyclic cage compounds have been drawing the atten-
tion of organic chemists since the middle of the last century.
Interest in the pharmacology of polycyclic cage amines was
stimulated by early findings that adamantane amine, 1-
amino-adamantane or amantadine, had antiviral activity
“the polycyclic cage structure seems to be ideally suited for
[
1,2]
against a variety of viruses, including influenza,
hepati-
developing multiple mechanism drugs, as it can both serve
as a scaffold for the drug molecule proper, or as a moiety
that may be added to improve the pharmacokinetic proper-
ties of drugs currently used in the clinic, or drug candidates
[
3,4]
[5,6]
tis C
and herpes zoster neuralgia.
Amantadine is a
specific inhibitor of the M2 ion channel of the influenza
virus and is believed to form a hydrogen bond with a histi-
dine residue (His-37) in the M2 protein, effectively blocking
[24]
under development.”
[
7]
the ion channel.
Both, adamantane (1) (T symmetry) and D -symmetri-
d
3
Interest in the pharmacology of polycyclic cage com-
pounds was further stimulated when a variety of ada-
mantane derivatives with a wide range of pharmacological
properties were synthesized. Adamantane is found in dif-
ferent drugs [memantine, remantadine, midantane
and adapromine (drugs against flu, tick-borne encephali-
2,6 3,10 5,9
cal
undecane (2), have a relatively large hydrocarbon cage size
ca. 5.5 Å), high lipophilicity and are conformationally ri-
trishomocubane,
pentacyclo[6.3.0.0 .0 .0 ]-
(
gid. The last two properties are particularly very important
for drugs. Additionally, they both are stabilomers (the most
thermodynamically stable of all possible isomeric C H
16
[8]
[9]
[10]
[
11]
10
[12]
[13]
tis, CNS diseases), gludantan, bemantane and himan-
and C H , respectively).
11
14
tan[ (Parkinson’s disease), dimantane (CNS disease) and
14]
[
15]
kemantane
(HIV and chronic fatigue syndrome)]. Evi-
dently the polycyclic cage is useful both as a scaffold for
sidechain attachment and to improve drug lipophilicity. Ad-
ditionally, polycyclic cage compounds can be used as poly-
meric compounds,[
16–19]
polymer materials
[20]
and thermo-
[
[
a] Department of Organic Chemistry,
Although 2 was synthesized in 1970,[25] to date there have
been less than 100 articles published on the synthesis and
National Technical University of Ukraine,
Pr. Pobedy 37, 03056 Kiev, Ukraine
E-mail: lia@xtf.ntu-kpi.kiev.ua
[26]
reactivity of D -trishomocubane and its derivatives. It is
3
b] Computer-Chemie-Centrum and Interdisciplinary Center for
Molecular Materials, University Erlangen-Nuremberg,
Nagelsbachstr. 25, 91052, Erlangen, Germany
also one of the symmetrical cage hydrocarbons that has
planar chirality. Hence, its optical activity offers capabilities
inaccessible to most other cage compounds, allowing 2 to
find application virtually everywhere adamantane deriva-
tives are used.
Fax: +49-(0)9131-85-26565
E-mail: Tatyana.Shubina@chemie.uni-erlangen.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001731.
2554
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2554–2561

A Convenient Road to 1-Chloropentacycloundecanes
Nonetheless, derivatives of 2 remain virtually unex- droxy- (6), 1-fluoro- (7a), 1-bromo- (7b), 1-carboxy- (7c)]
plored. The reasons for this are limited synthetic methods, from 2, Cookson’s diketone 4, and tetracyclo[6.3.0.04 .0 ]-
.11 5,9
harsh reaction conditions, and often unsatisfactory yields undecane-2,7-dione (5), usually in harsh environments or
of the desired D -trishomocubane derivatives. The majority with low yields (Scheme 1).
3
of synthetic routes to 2 and its derivatives are based on
Although it is possible to synthesize various precursors
rearrangements of the carbon cage of isomeric cage struc- (i.e. 6, 7a–c, Scheme 1) by substitution reactions, the main
tures, usually pentacyclo[5.4.0.02,6.0 .0 ]undecane (Cs- difficulty is the introduction of a substituent into the C -
3,10
5,9
1
trishomocubane, 3).
position of 2.
4
While C derivatives of D -trishomocubanes are the most
Both 4 and 5 can be easily synthesized by Diels–
3
1
2
studied, tertiary C and C substituted precursors (hydroxo-, Alder reactions. Consequently, another method to synthe-
halo-, etc.) are difficult to synthesize. There are few synthetic size 1-functionalized D -trishomocubane is to start
3
routes that yield 1-substituted D -trishomocubane and with appropriately substituted precursors for the Diels–
3
Alder reaction. Previously reported by Nakazaki,[
32]
none can be regarded as preparative.
The most popular technique used to synthesize substi- 1-functionalized D -trishomocubane 15 was synthesized by
3
tuted compounds is to use chemical methods to modify the isomerization of monosubstituted Cookson’s diketone
functional groups on a skeleton (Scheme 1).
10 according to Scheme 2. Unfortunately, formation
have synthe- of the 2-substituted derivative 17 as a side product takes
Kukhar and coworkers[
27–30]
and Kent
[31]
sized a number of 1-substituted D -trishomocubanes [1-hy- place.
3
3
Scheme 1. General scheme for the synthesis of 1-substituted D -trishomocubanes. Only the main structures are noted. Conditions and
reagents are shown for the main step of each reaction when the trishomocubane structure is formed.
3 3
Scheme 2. Synthesis of (1-D -trishomocubyl)- (15) and (2-D -trishomocubyl)- (17) acetic acids.
Eur. J. Org. Chem. 2011, 2554–2561
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2555

I. A. Levandovskiy, T. E. Shubina, et al.
FULL PAPER
Thus, we have developed an efficient route to 1-substi-
tuted D -trishomocubanes.
3
Results and Discussion
It is known that under acidic conditions or Lewis acid
catalysis, C -trishomocubane 3 usually undergoes skeleton
s
isomerization into a D -cage. This is believed to proceed Scheme 4. Adducts of the Diels–Alder reaction of cyclopentadiene
3
8
with 2-substituted-1,4-quinones.
through the formation of the C -trishomocubane C (or
equivalent C ) cation, followed by a 1,2-shift, and forma-
s
1
1
4
[31]
tion of the D -trishomocubane C cation (Scheme 3).
3
Thus, we decided to introduce a chlorine atom into the C1
leading to the adduct according to pathway A (Scheme 4).
2
-Methylquinone was reported to give the adduct that re-
sults from reaction with an unsubstituted double bond
pathway B, Scheme 4).
position of C -trishomocubane and then pursue rearrange-
ment in an acidic environment. Moreover, despite the vari-
ety of C -trishomocubane derivatives, to the best of our
knowledge C -substituted C -trishomocubane and 1-
s
(
s
[
36]
1
Our calculations (Scheme 5) suggest that the Diels–Al-
s
der reaction of 2-chloro-1,4-quinone with cyclopentadiene
should proceed as an inverse Diels–Alder reaction. Forma-
tion of the adduct formed through pathway B is more
favourable (both kinetically and thermodynamically) over
that formed by pathway A (Schemes 4 and 5). The lowest
activation barrier is found to be 11.7 kcal mol–1 and the
corresponding transition state describes formation of the
endo-adduct formed through pathway B (Scheme 4).
chloro-D -trishomocubane have not been reported.
3
s
Scheme 3. Proposed rearrangement pathway from C -trishomocub-
Thus, in order to introduce a chlorine atom into the
pentacycloundecane cage we have used a Diels–Alder reac-
tion between cyclopentadiene and 2-chloro-1,4-quinone. In
ane to D -trishomocubane.
3
The Diels–Alder reaction between cyclopentadiene and the first step of the reaction, 2-chloroquinone (20, 90%
quinones followed by intramolecular photocyclization leads yield) is formed according to Scheme 6. The Diels–Alder
to the formation of the C -trishomocubane skeleton. The reaction of 20 with cyclopentadiene afforded the sole iso-
s
endo adduct is usually favoured, and in the case of substi- lable product 21 (77% yield), which gives 1-chloropentacy-
tuted quinones, reaction with either substituted or unsubsti- clo[5.4.0.02 .0
,6
3,10. 5,9
0
]undecane-8,11-dione (22) upon pho-
tuted double bonds are possible. For example, 2-nitroqui- tocyclization. Reduction of 22 with hydrazine hydrate af-
[
33]
[34]
[35]
2,6 3,10. 5,9
none,
2-acetylquinone
and 2-carbometoxyquinone
fords 1-chloropentacyclo[5.4.0.0 .0
0 ]undecane (23)
react with cyclopentadiene by a substituted double bond in 50% yield (Scheme 6).
–
1
Scheme 5. Energy diagram of Diels–Alder reaction of cyclopentadiene with 2-chloro-1,4-quinone [energies are given in kcalmol ,
B3PW91/6-31G(d,p)].
2556
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A Convenient Road to 1-Chloropentacycloundecanes
s
Scheme 6. Synthesis of 1-chloro-C -trishomocubane 23.
Table 1. Relative stabilities of cations 3a –3f and 2a –2c+ (–E + ZPE, kcalmol , relative to 3e ).
+
+
+
–1
+
As mentioned above, under acidic conditions 1-chloro-
C -trishomocubane 23 should undergo rearrangement to
s
form 1-chloro-D -trishomocubane. Hydride abstraction
3
+
from 3 leads to the formation of six possible cations (3a –
f , Table 1 and Figure S1) and, in the case of 2, to three
cations (2a –2c , Table 1 and Figure S1).
As implied by our calculations (Table 1) the C cation
3e ) is most stable. The other C -trishomocubane cations
+
3
+
+
+
8
+
(
s
in the series are less stable [B3PW91/6-311+G(d,p) +ZPE]:
+
8
+
+
9
+
+
1
+
+
4
+
C (3e , 0.0) Ͻ C (3f , 4.2) Ͻ C (3a , 8.4) Ͻ C (3d ,
+
2
+
+
3
+
9
.2) Ͻ C (3b , 9.8) Ͻ C (3c , 11.7). At the MP2/cc-
+
4
pVDZ level the trend is similar; however, the C cation
+
Figure 1. Geometry of cation 3e , which is equivalent to cation
+
+
(3d ) is a transition structure between two 3c cations. The
+
2c
[bond lengths in Å, B3PW91/6-31G(d) (first entry), B3PW91/
+
+
2
a and 2c cations are predicted to be isoergic, and the 6-311+G(d,p) (second entry) and MP2/cc-pVDZ (third entry)].
+
+
–1
C -symmetric cation 2b lies above 2c by 7.9 kcal mol
3
(
Table 1 and Figure S1).
+
Careful inspection of the geometry of cation 3e revealed and 1-chloro-D -trishomocubane is not formed. NMR
3
+
that it is equivalent to 2c (Figure 1 and Table 1). It also and GS/MS spectra confirm the presence of unreacted 23
should be noted that this process is not a 1,2-hydrogen shift, only.
as proposed earlier (Scheme 3), rather a 1,2-alkyl shift.
This unexpected result prompted us to look for another
Therefore, acidic rearrangement of 3 should readily give a way to obtain 1-chloro-D -trishomocubane. Thus we have
3
derivative with a D -moiety.
modified a method that uses chlorosulfation of diketones
3
[
39]
It is worth noting that of nine possible cations all except and leads to the insertion of a chlorine atom.
The first
+
+
[37]
2
b and 3f (Figure S1) have closed C–C–C 3c–2e bonds,
step of the reaction is the chlorosulfation of Cookson’s di-
[38]
and are thus nonclassical cations.
ketone 4 (Scheme 7). This was performed in CHCl , as op-
3
1
Consequently, we have attempted to access the C -deriva- posed to the conditions used previously (HSO Cl), for a
3
tive of 2 by a different route: through the 1-substituted Co- few hours (increasing the reaction time up to a few days
okson’s diketone. We have modified Kent’s[31] synthetic pro- increases yield only by a few%). Under these conditions 1-
cedure by substituting AlCl into CCl /CH Cl . Cage re- chloro-11-chlorosulfapentacyclo[6.3.0.02 .0 .0 ]undec-
,6
3,10 5,9
3
4
2
2
arrangement does not take place under these conditions ane-7-one (24) and 1,11-dichloro[6.3.0.02 .03,10.05,9]undec-
,6
Eur. J. Org. Chem. 2011, 2554–2561
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2557

I. A. Levandovskiy, T. E. Shubina, et al.
FULL PAPER
ane-7-one (25) are obtained (Scheme 7). Chlorosulfate 24
The oxidation of chloro ketol 26, which gives 1-chloro-
can be easily hydrolyzed to chloro ketol 26 by boiling in pentacyclo[6.3.0.02 .0 .0 ]undecane-7,11-dione
,6
3,10 5,9
(27)
solution of aqueous ammonia. The total yield of 26 from (Scheme 9) was attempted with different oxidizing agents.
two steps is 75%. A yield of 64% was reported by Tolstikov Oxidation with Jones reagent, CrO /acetic acid and
3
et al. in the original work.[ The reaction product contains KMnO /acetonitrile/water, leads to a low conversion.
39]
4
2
,6 3,10 5,9
up to 12% admixture of 1,11-dichloro[6.3.0.0 .0 .0 ]- Furthermore, with the increase of temperature or time, the
undecane-7-one (25), which can be separated chromato- yield of byproducts also increases. The best yields (81%) for
graphically on Al O .
the oxidation of 26 were obtained using pyridinium chloro-
chromate (PCC). The results of oxidation are summarized
in Table 2.
2
3
Scheme 7. Chlorosulfation of Cookson’s diketone 4.
Scheme 9. Synthesis of 1-chloro-D
3
-trishomocubane (28) and 1-
The proposed mechanism of the chlorosulfation of
Cookson’s diketone 4 is summarized in Scheme 8. The first
step is the reaction of one of the keto groups with HCl.
chloro-D -trishomocubane-11-ol (29).
3
A Wolff–Kishner reaction of 27 affords 1-chloro-D -tri-
3
Further protonation and the release of water leads to 8- shomocubane (28) in 78% yield. It should be noted that in
2
,6 3,10. 5,9
chloropentacyclo[5.4.0.0 .0
0
]undecane-11-one. This the course of the reaction a white solid sublimes in the re-
cation can easily [ΔEact
=
+4.7 kcalmol–1 and flux condenser. The same reaction with the chloro diketone
–
1
+
0.7 kcalmol , B3PW91/6-31G(d,p) and MP2/cc-pVDZ, containing a mixture of nonoxidized chloro ketol 26 affords
respectively] undergo skeleton rearrangement to form a 1-chloro-D -trishomocubane-11-ol (29) (75% yield). In this
3
nonclassical cation with a D -trishomocubane structure. case, after sublimation of 28, 29 can be easily extracted
3
–
–
This cation can further react with SO Cl and Cl to form from the aqueous layer of the reaction mixture into chloro-
2
24 and 25, respectively.
form.
Scheme 8. Plausible reaction pathway of the chlorosulfation of Cookson’s diketone 4 [B3PW91/6-31G(d,p) and MP2/cc-pVDZ, –E +
–1
ZPE, kcalmol ].
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Eur. J. Org. Chem. 2011, 2554–2561

A Convenient Road to 1-Chloropentacycloundecanes
ing to a literature method,[56] which uses the Diels–Alder reaction
Table 2.
[
Oxidation
of
1-chloro-11-hydroxypentacyclo-
6.3.0.02,6.03,10.0 ]undecane-7-one (26).
5,9
of p-benzoquinone and cyclopentadiene to yield endo-tricy-
2
,7
clo[6.2.1.0 ]undeca-4,9-dien-3,6-dione. Irradiation (low-pressure
mercury UV lamp, 300 W) of the diene-dione in ethyl acetate gave
Oxidizing agent
Temp.
°C]
Time % Yield % Yield
[h]
% Yield
[
of 27
of 26
of byproducts
56]
1
4
in 90% yield; m.p. 240.0–242.0 °C, ref.[ 245 °C. H NMR (500
Jones reagent
20
2
10
40
6
15
24
38
35
48
31
8
37
45
54
54
MHz): δ = 2.6–3.3 (m, 8 H), 1.9–2.0 (m, 2 H) ppm. GC–MS (τ =
.277): m/z (%) = 174.00 (100), 117.00 (92.96), 91.05 (44.14), 118.00
35.68), 66.05 (35.01).
20
20
30
8
(
11
p-Benzoquinone (18), 2-Chloro-hydroquinone (19) and 2-Chloro-1,4-
quinone (20): Compounds 18, 19 and 20 were prepared according
to literature methods.[
CrO
3
, acetic acid
20
10
20
30
51
52
19
18
30
20
57–59]
KMnO
acetonitrile/water
4
,
20
20
10
40
5
24
95
68
–
8
4-Chloro-tricyclo[6.2.1.02,7]undeca-4,9-diene-3,6-dione (21): To
a
solution of 20 (30 g, 0.21 mol) ethanol (100 mL) was added cyclo-
pentadiene (17.5 mL, 13.86 g, 0.21 mol) dropwise under constant
stirring and cooling. From the pink solution the product precipi-
tated as white crystals, which were collected by filtration and
PCC,
dichloromethane
40
40
10
18
40
72
81
79
18
7
2
10
12
19
40
1
washed with ethanol; yield 38.8 g (90%). H NMR (500 MHz,
Conclusions
CDCl ): δ = 1.50 (m, 2 H), 3.31 (m, 2 H), 3.52 (m, 2 H), 6.06 (s, 2
H), 6.84 (s, 1 H) ppm.
3
In summary, we have developed an efficient method to
obtain 1-chloropentacycloundecanes through simple trans-
formations, involving Diels–Alder reactions and the chloro-
sulfation of Cookson’s diketone. Previously unknown 1-
chloro-D -trishomocubane and other derivatives of D -tri-
1
-Chloropentacyclo[5.4.0.02,6.03,10.0 ]undeca-8,11-dione (22): Irra-
5,9
2
,7
diation of 1-chlorotricyclo[6.2.1.0 ]undeca-8,11-dione (21) was
carried out in a reaction vessel fitted with a quartz immersion well
with a medium pressure mercury vapour lamp (300 W). The reac-
tion was carried out on a solution of 21 (20 g) in dry ethyl acetate
3
3
shomocubane have been synthesized. A possible reaction
mechanism has been proposed on the basis of mechanistic
(
500 mL). The reaction mixture was purged with argon for five
minutes and irradiated for 48 h at room temperature under con-
studies. Due to the availability of the starting materials, stant argon purging. After evaporation of the solvent and column
mild reaction conditions and potential of the products, this chromatography (Al column; eluent: CH Cl ) Compound 22
method may be useful in organic synthesis, materials sci- was obtained as white crystals (17.4 g, 87%); m.p. 86.0 °C.
2
O
3
2
2
1
H
NMR (500 MHz, CDCl
m, 3 H), 3.30 (m, 1 H) ppm. C NMR (125 MHz): δ = 36.98,
1.06 (secondary), 43.72, 44.06, 49.81, 51.44, 54.28, 54.59, 64.76
3
): δ = 2.02 (q, 2 H), 2.86 (m, 3 H), 2.96
ence and medicinal chemistry.
1
3
(
4
(
(
quaternary, CCl), 204.15, 208.06 ppm. GC–MS (τ = 11.239): m/z
%) = 208 (97.109); (τ = 11.838): m/z (%) 252 (2.891).
Computational Methods
Geometries were optimized at the MP2[40,41]/cc-
-Chloropentacyclo[5.4.0.02,6.03,10.05,9]undecane (23): To 22 (1.04 g)
1
[
42]
[43–47]
[48–52]
pVDZ,
B3PW91
/6-31G(d,p)
and B3PW91/6-
was added a 10-fold molar excess of hydrazine hydrate (2.5 g) and
diethylene glycol (8 mL). After 8 h of constant stirring at 135 °C,
311+G(d,p) levels of theory including frequency analyses to
disclose the nature of the stationary points (Nimag = 0 for KOH (1.4 g) was added and the temperature was gradually in-
s
minima and Nimag = 1 for transition structures) as im- creased. 1-chloro-C -trishomocubane 23 sublimed as a white solid
plemented in the Gaussian 09 program package.[ Relative in the reflux condenser. The product was dissolved from the con-
53]
denser with ethyl ether; yield 0.68 g (76%). GC–MS (τ = 8.141):
energies are Zero Point Energy (ZPE) corrected at all levels.
1
m/z (%) = 180 (100). H NMR (500 MHz, CDCl
3
): δ = 1.171 (dt,
The reaction pathways along both directions from the tran-
[
54]
1 H), 1.250 (d, 1 H), 1.475 (dd, 1 H), 1.645 (d, 1 H), 1.699 (d, 1
H), 1.840 (d, 1 H), 2.200–2.300 (m, 2 H), 2.329 (m, 1 H), 2.434 (s,
sition structures were followed by the IRC method.
1
3
1
H), 2.687–2.920 (m, 2 H), 2.849 (s, 1 H) ppm. C NMR (125
MHz, CDCl ): δ = 28.08, 34.20, 36.25 (secondary), 40.29, 40.50,
1.54, 45.82, 45.89, 48.78, 53.76 (tertiary), 69.40 (quaternary) ppm.
Isomerization of 1-Chloropentacyclo[5.4.0.02,6.03,10.05,9]undecane
23): Aluminium chloride (two to three times the weight of the
3
Experimental Section
General: 1H (500 MHz) and 13C NMR (125 MHz) spectroscopy
4
measurements were carried out with a Bruker Avance 500 MHz
(
spectrometer; solvent: CDCl
3
, internal standard: tetramethylsilane
hydrocarbon) was added to a carbon tetrachloride solution of 23.
The reaction mixture was stirred at room temperature for 2 h and
then poured on to ice. The organic phase was separated and dried
with anhydrous magnesium sulfate before the solvent was removed.
Only unreacted 23 was isolated, which was confirmed by GC–MS
and NMR spectra.
1
13
(TMS). H and C NMR chemical shifts are reported in parts per
million downfield from TMS. Mass spectroscopy was carried out
with an Agilent 5890 Series II 5972 GC–MS spectrometer.
Pyridinium Chlorchromate (PCC): PCC was prepared according to
[
55]
a literature method. The addition of chromium(VI) oxide (25 g,
.25 mol) to hydrochloric acid (6 n, 46 mL, 0.28 mol) gives the
unstable chlorochromic acid. Subsequent addition of pyridine
19.7 g, 0.25 mol) at 0 °C immediately gave pyridinium chlorochro-
mate as yellow-orange solid (45 g, 84%).
0
Reaction of Cookson’s Diketone (4) with Chlorosulfonic Acid: Chlo-
rosulfonic acid (94 mL, 1.43 mol) was added dropwise to a cold
stirred solution of 4 (50 g, 0.287 mol) in chloroform (400 mL) and
the mixture immediately turned black. After 24 h of stirring, the
reaction mixture was poured into ice. The chloroform was sepa-
rated and the aqueous phase was washed with chloroform. The
(
Pentacyclo[5.4.0.0 .03,10.05,9]-undecane-8,11-dione (4): Pentacy-
2,6
clo[5.4.0.02 .0 0.05,9]-undecane-8,11-dione was prepared accord-
,6
3,1
Eur. J. Org. Chem. 2011, 2554–2561
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2559

I. A. Levandovskiy, T. E. Shubina, et al.
FULL PAPER
combined chloroform phases were washed with water until the pH
into chloroform. GC–MS (τ = 10.191): m/z (%) = 66.10 (100), 79.15
=
6. After drying with anhydrous Na
to obtain the product as a yellow solid (75 g). GC–MS: 4 1.55%,
4 69.91%, 25 12.51%, 26 16.02%. GC–MS (24) (τ = 10.730): m/z
%) = 66.05 (100), 129.00 (36.13), 115.15 (28.79), 39.05 (21.06),
2
SO
4
the solvent was removed
(89.47), 75.15 (83.12), 161.10 (65.75), 95.10 (62.01).
Supporting Information (see footnote on the first page of this arti-
cle): Gaussian archive entries of the optimized structures; NMR
spectra of new compounds.
2
(
117.00 (19.54).
1
-Chloro-11-hydroxypentacyclo[6.3.0.02,6.03,10.05,9]undecane-7-one
(
26): To the mixture obtained from the reaction of 4 with chlorosul- Acknowledgments
fonic acid as described above (40 g) was added ammonia solution
25%, 800 mL). The reaction mixture was heated under reflux for
h, extracted into chloroform, dried and filtered. A brown
(
2
This work was supported by the State Basic Research Fund of
Ukraine (grant from the President of Ukraine to young scientists).
We thank “Macrochem” and “UkrOrgSynthesis” for support.
amorphous substance (25 g) was obtained after evaporation of the
solvent. The products were separated with column chromatography
2 3
on Al O . Elution with 10% ethyl acetate/hexane on gave dichloro
ketone 25 as a white solid. Chloro ketol 26 was eluted from the
chromatographic column with methanol. After evaporation of
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1.5%, 26 88.5%. 26: H NMR (500 MHz, CDCl
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2561