Solvent-induced, selective rearrangement of hydrogen cubane-1,4- dicarboxylate to hydrogen cuneane-2,6-dicarboxylate

Article abstract of DOI:10.1016/j.tet.2013.04.056

The rearrangement of cubane-1,4-dicarboxylic acid in water to cuneane-2,6-dicarboxylic acid is presented. The reaction is not a transition metal catalyzed, rather a solvent-promoted transformation, and the reaction proceeds via the semi-dissociated form of the cubane diacid, hydrogen cubane-1,4-dicarboxylate. No other, 1,3-disubstituted cuneane isomer is formed. The reaction is significantly accelerated by the addition of 1 equiv of base, suggesting that the hydrogen cubane-1,4-dicarboxylate ion plays a key role in this new type of rearrangement.

Full text of DOI:10.1016/j.tet.2013.04.056

Tetrahedron xxx (2013) 1e4
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Tetrahedron
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Solvent-induced, selective rearrangement of hydrogen cubane-1,4-
dicarboxylate to hydrogen cuneane-2,6-dicarboxylate
*
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Gabor Durko , Istvan Jalsovszky
€
€
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Department of Organic Chemistry, Institute of Chemistry, Eotvos Lorand University, P.O. Box 32, H-1518 Budapest, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
The rearrangement of cubane-1,4-dicarboxylic acid in water to cuneane-2,6-dicarboxylic acid is pre-
sented. The reaction is not a transition metal catalyzed, rather a solvent-promoted transformation, and
the reaction proceeds via the semi-dissociated form of the cubane diacid, hydrogen cubane-1,4-
dicarboxylate. No other, 1,3-disubstituted cuneane isomer is formed. The reaction is significantly accel-
erated by the addition of 1 equiv of base, suggesting that the hydrogen cubane-1,4-dicarboxylate ion
plays a key role in this new type of rearrangement.
Received 8 February 2013
Received in revised form 26 March 2013
Accepted 15 April 2013
Available online xxx
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
Strained molecules
Rearrangement
Chemoselectivity
1. Introduction
analogous compounds, however, these rearrangements pre-
sumably follow a mechanism different from the transition metal
Transition metal catalyzed skeletal rearrangements of strained
systems have been known since the 1970s.1e5 Among these, one of
the first described examples is the transformation of cubane to
cuneane. Silver(I) perchlorate or palladium(II) chloride catalyzed
this rearrangement which, in the case of substituted cubanes,
afforded mixtures of cuneane isomers (Fig. 1).6e8 According to the
proposed mechanism, oxidative addition of the metal ion to a CeC
bond is followed by carbonium ion formation and rearrangement.9
Lithium(I) with a weakly coordinating carborane anion was also
used to induce a skeletal rearrangement on cubane and some
catalyzed transformation.10 Apart from Ag(I), Pd(II), and Li(I), no
other species was found to induce a rearrangement to cuneane.
Theoretical calculations suggest that protonation11 or single elec-
tron transfer oxidation12 of cubane may also result in a rearrange-
ment leading either to cuneane or to pentalenes, but experimental
proof seems to be controversial.13
Ring opening reactions affording tricyclooctadiene or cyclo-
octatetraene, have also been reported. Conversion of cubane to syn-
tricyclooctadiene is induced by rhodium(I) ions14 or lithium diiso-
propylamide.15 This intermediate can be converted to cyclo-
octatetraene upon heating.16 Direct thermal ring opening of
cubanes is also possible without catalyst17 and even without sol-
vent.18 It was also reported that thermal rearrangement of cuneane
affords the isomeric cyclooctatetraene via semibullvalene.19 4-
Iodo-1-vinylcubane was found to rearrange to 4-vinyl-trans-b-
1
2
iodostyrene through a cyclooctatetraene intermediate.20
R
R
1
1
R
6
R
2
2. Results and discussion
3
4
R
R
Previous studies on the cubaneecuneane rearrangement were
limited to the parent compound and a few ester derivatives, while
substituent effects seem to have a significant influence on the
outcome of the reaction.6 Also no detailed study has been devoted
to the conditions of the rearrangement. Our aim was to investigate
how solvent polarity, temperature, and the concentration of the
catalyst or other additives affect reaction rate and product/isomer
distribution. Whereas previous studies have been dealt with less
3a, R = COOMe
3b, R = CH2OAc
4a (5%)
4b (83%)
5a (95%)
5b (17%)
Fig. 1. Cubanedcuneane rearrangement.
* Corresponding author. Tel.: þ36 1 372 2500/1216; fax: þ36 1 372 2592; e-mail
ꢀ
address: gdurko@elte.hu (G. Durko).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.056
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G. Durko, I. Jalsovszky / Tetrahedron xxx (2013) 1e4
Table 1
polar derivatives, we have chosen a water-soluble model com-
Rearrangement of cubane-1,4-dicarboxylic acid (6) in various media
pound, cubane-1,4-dicarboxylic acid (6).
Solvent
Bp [ꢁC] Conditions
Yield of 7 [%] Yield of 8 [%]
Water
Acetic acid
100
119
Reflux/11 h
Reflux/12 h
185 ꢁC/5 bar/12 h
Reflux/12 h
Reflux/12 h
Reflux/12 h
Reflux/12 h
Reflux/12 h
Reflux/12 h
180 ꢁC/12 h
180e190 ꢁC/12 h
25 ꢁC/12 h
3%
5%
d
d
2.1. The effect of catalyst concentration
d
25%
3%
21%
d
Upon investigation of the silver(I) catalyzed rearrangement of
cubane-1,4-dicarboxylic acid (6) in water using silver nitrate as
catalyst, we have found that the catalytic effect of the Ag(I) ion
could be initiated using 10ꢀ4 equiv of the catalyst (Fig. 2).
Propanoic acid
Pentanoic acid
Toluene
1-Nitropropane 131
DMF
Diglyme
DMSO
Sulfolane
H2SO4 98%
HBr 62%
HCl 37%
141
186
111
5%
d
d
d
d
153
162
189
285
d
da
da
d
d
Rearrangement also occurs in lower concentrations, independent
from Ag(I) concentration. We got the same yields (2e4% at 135 ꢁC/
1.6 bar/3 h) even without any added silver nitrate. Although deion-
ized, conductivity grade water and purified materials were used,
obviously the silver(I) concentration could not be reduced to ‘zer-
o’dICP-MS analysis of the starting materials and the solvent showed
that the ‘residual’ silver(I) concentration was 4.6 ng/mL, which is
5ꢂ10ꢀ7 equivalents relative to the cubane diacid. However, this
amount is well below the 10ꢀ4 equivalent limit, therefore no catalytic
effect can be attributed to silver(I) ions in such low concentrations.
d
36%
71%
d
d
d
d
100 ꢁC/12 h
Reflux/12 h
db
dc
d
d
d
a
Starting material partially decomposed.
b
c
Bond cleavage and HBr addition21 was observed.
Starting material fully decomposed.
Ag or
protic solvent
COOH
HOOC
HOOC
7
HOOC
6
COOH
over 135°C
COOH
8
Fig. 3. Rearrangement of cubane-1,4-dicarboxylic acid (6).
However, the addition of base (potassium hydroxide) resulted in
higher yields. The maximum cuneane yield was achieved with 1
molar equivalent of KOH relative to the dicarboxylic acid 6 (Fig. 4),
which corresponds to the semi-dissociated form, hydrogen cubane-
1,4-dicarboxylate (6b). The same results were obtained with other
bases, such as sodium hydroxide, potassium carbonate and sodium
carbonate. After neutralization and workup of the samples, NMR
Fig. 2. The effect of silver(I) concentration on the rearrangement of cubane 6 to cu-
neane 7 (10 mg of 6 in 0.5 mL aqueous AgNO3 solution at 135 ꢁC/3 h) (Yields were
determined by 1H NMR after workup.).
100%
80%
2.2. The effect of solvent
The ‘silver-free’ rearrangement of cubane-1,4-dicarboxylic acid
(6) to cuneane-2,6-dicarboxylic acid (7) was examined in various
solvents at (or near to) reflux temperature (Table 1). Transformation
to cuneane was observed only in polar protic media (water and
carboxylic acids). In polar aprotic solvents decomposition (e.g., in
DMF and diglyme) or cage opening to cyclooctatetraene-1,4-
dicarboxylic acid (8) occurred (e.g., in DMSO and also in sulfolane).
This thermal ring opening affording cyclooctatetraene was also ob-
served in polar protic solvents at elevated temperature (Fig. 3).
60%
cubane 6
cuneane 7
40%
20%
0%
2.3. The effect of pH and acid dissociation
In order to get a better insight into the role of protic media in the
rearrangement, the pH dependence of the reaction was examined
in water at 135 ꢁC/1.6 bar, and was found to be significant. Strongly
acidic media (pH 2, HCl/H2O) inhibited cuneane formation, so
a direct acid-catalyzed mechanism is unlike. This assumption is in
agreement with the work of Olah and his co-workers who pro-
tonated cubane-1,4-dicarboxylic acid (6) in superacids, and the
resulting cubyl carboxonium ions did not rearrange.22
0
1
2
3
4
KOH [equiv.]
Fig. 4. The effect of acid dissociation on the rearrangement of cubane 6 to cuneane 7
(10 mg of 6 in 0.5 mL aqueous KOH solution at 135 ꢁC/3 h) (The ratio of 6 and 7 in the
crude product was determined by 1H NMR after workup, using the solvent signal as an
internal integration reference.).
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G. Durko, I. Jalsovszky / Tetrahedron xxx (2013) 1e4
3
analysis showed only the presence of the cuneane product and the
40
30
20
10
0
unreacted starting material, along with an insoluble tarry byprod-
uct. The material balance (composition of the crude reaction mix-
ture) is presented on Fig. 4.
The dependence of species distribution on the base/acid ratio in
these solutions was calculated with Hyss2009 software23 (Fig. 5).
The higher the concentration of the semi-dissociated form of the
cubane diacid (6b), the higher the ratio of its rearrangement to
cuneane. No cuneane was formed when more than 2 equiv of base
were added, in this case the diacid is fully dissociated and virtually
no hydrogen cubane-1,4-dicarboxylate (6b) is present.
cuneane 7
COT 8
140
150
160
170
180
190
Temperature [°C]
0.10
0.08
0.06
Fig. 6. Product distribution as a function of temperature in the rearrangement of cu-
bane 6 to cuneane 7 and cyclooctatetraene (COT) 8 in pressurized water (10 mg 6 in
0.5 mL H2O, reaction time: 60 min).
perchlorate in benzene or toluene.6e8 We also observed this se-
lectivity in the case of the silver(I) nitrate catalyzed rearrangement
of the cubane diacid 6 in water. While the diacid and its dimethyl
ester can not be directly compared, a likely explanation to this
difference might be that there is an equilibrium between the 1,3-
and 2,6-disubstituted cuneane isomers, and the higher tempera-
ture applied in our experiments favors the formation of the 2,6-
derivative, which is thermodynamically more stable.7
free Cub (6a)
CubH (6b)
0.04
CubH2 (6)
The decrease in the concentration of the cuneane product along
with the increase of cyclooctatetraene concentration upon pro-
longed heating (Fig. 6) may suggest that the cuneane diacid also
rearranges to the corresponding cyclooctatetraene derivative.19
However, when we heated in pure form, cuneane-2,6-
dicarboxylic acid (7) did not rearrange to cyclooctatetraene diacid
8 neither in protic nor in aprotic media nor under solvent-free
conditions, only slow decomposition was observed, affording an
insoluble tarry material.
0.02
0.00
0
1
2
3
4
KOH [equiv.]
Fig. 5. Calculated species distribution in solutions of cubane diacid 6 containing dif-
ferent quantities of KOH (Cub: cubane-1,4-dicarboxylate (6a), CubH: hydrogen cubane-
1,4-dicarboxylate (6b), CubH2: cubane-1,4-dicarboxylic acid (6)).
2.6. Mechanism
The concentration dependence of the silver-free rearrangement
reaction also supports the key role of the semi-dissociated form.
Cuneane yield is in inverse proportion to the initial cubane concen-
tration: the more dilute the solution, the higher the yield. As cubane-
1,4-dicarboxylic acid (6) is a weak acid (pKa values are 5.43 and 6.23,
respectively24), in dilute solutions the ratio of the dissociated form
(6b) is higher. When the carboxyl function was transformed to di-
methyl amide to prevent dissociation, no cuneane was formed.
A possible mechanism for the reaction is shown on Fig. 7. In the
second step there is a 1,2 bond shift from C(4)eC(5) to C(4)eC(2). It
should be noted that, because of the symmetry of intermediate 9,
C(3) and C(5) are equivalent, so a C(4)eC(3) to C(4)eC(2) bond shift
is equally possible, and because of the chirality of cuneane-2,6-
dicarboxylic acid (7), the alternative route leads to an enantio-
meric product. In this step the positive charge is transferred from
a four-membered ring to a five-membered ring, which might be
one of the driving forces of the rearrangement.
2.4. The effect of temperature
3. Conclusion
Preliminary experiments in aqueous media were carried out at
reflux conditions, but later we changed to sealed disposable glass
ampoules, which have the advantage that the solution can be
heated to over 100 ꢁC under pressure, and it is also easier to keep
away interfering silver(I) ions as if flasks and reflux condensers
were used. Elevating the temperature over 100 ꢁC enabled higher
cuneane yields but that is limited by the decomposition of
cuneane-2,6-dicarboxylic acid (7) and the thermal ring opening of
the starting cubane dicarboxylic acid 6 to cyclooctatetraene diacid
8, which is favored at higher temperatures (Fig. 6).
As predicted by quantum chemical calculations11,12 and shown
by an earlier example,10 species other than transition metal ions
may be able to bring about skeletal rearrangements in strained ring
systems. However, no attempt was made to carry out the rear-
rangement of cubane derivatives in polar media. In this paper we
presented that cubane-1,4-dicarboxylic acid (6) rearranges selec-
tively to the corresponding 2,6-cuneane derivative 7 in aqueous
media with no transition metal ion added. While obviously the
presence of a trace amount of silver(I) ions can not be fully ex-
cluded, the following observations prove indirectly that this re-
2.5. Isomer selectivity
action is not silver catalyzed, rather a solvent-promoted
transformation, and the reaction proceeds via the semi-
dissociated form of the cubane diacid, hydrogen cubane-1,4-
dicarboxylate (6b):
Under the conditions applied in our experiments (solvent: H2O,
135 ꢁC/1.6 bar, 1 equiv KOH added) the 2,6-derivative (7) was
formed selectively, whereas previous reports describe the forma-
tion of mixtures of cuneane isomers in the rearrangement of di-
methyl cubane-1,4-dicarboxylate (3a), induced by silver(I)
ꢃ The dilution effectdthe more dilute the solution of cubane
diacid, the higher the conversion rate to cuneane.
ꢀ
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4
G. Durko, I. Jalsovszky / Tetrahedron xxx (2013) 1e4
O
O
O
O
O
O
O
O
4
4
4
3
1
1
O
5
HO
1
5
3
O
5
3
O
O
HO
2
2
2
HO
HO
6b
9
10
7b
Fig. 7. Proposed mechanism for the rearrangement of hydrogen cubane-1,4-dicarboxylate (6b).
48.1, 45.3, 43.1. IR (ATR): 1662, 1440, 939, 858, 736 cmꢀ1. HRMS: m/z
calculated for C10H8O4eHþ (MeHþ): 191.0350; found: 191.0354.
ꢃ The base effectdthe reaction was significantly accelerated by
the addition of a base, and the maximum yield was achieved at
1 equiv of base relative to the cubane diacid, which corre-
sponds to the maximum concentration of hydrogen cubane
dicarboxylate (6b). The addition of more than 1 equiv of base
diminished reaction rate, and more than 2 equiv (complete
dissociation) prevented rearrangement.
ꢃ The acid effectdrearrangement was also prevented by the
addition of a strong acid, which protonates the dissociated
forms of the cubane dicarboxylic acid.
Acknowledgements
ꢀ
We thank Dr. Andras Bartha (Geological Institute of Hungary)
ꢀ
ꢀ
ꢀ
€
€
ꢀ
and Dr. Mihaly Ovari (Eotvos Lorand University, Budapest, Hun-
ꢀ
gary) for ICP-MS analysis, and Dr. Szabolcs Beni (Semmelweis
University, Budapest, Hungary) for an HRMS measurement. The
European Union and the European Social Fund have provided fi-
nancial support to the project under the grant agreement No.
ꢃ The silver ion effectdaddition of silver(I) ions to the samples in
concentrations even 2 orders of magnitude higher than origi-
nally present, did not affect the rate of rearrangement.
ꢀ
TAMOP 4.2.1./B-09/KMR-2010-0003.
Supplementary data
4. Experimental section
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.04.056.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
All conversions were determined by 1H NMR in DMSO-d6 after
workup, using the solvent peak as an internal integration reference.
Chemical shifts (d) are given in parts per million relative to tetra-
methylsilane. NMR spectra were recorded on a BRUKER Avance 250
spectrometer (1H: 250.13 MHz, 13C: 62.9 MHz). Starting materials
were checked for trace amounts of metals (such as Ag, Pd and Li) by
ICP-MS.
References and notes
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the diacid upon treatment with NaOH/H2O, then precipitated with
HCl/H2O, and washed thoroughly with distd water. The diacid was
recrystallized twice from glacial acetic acid, and was dried in vacuo
prior to use. Compound 6 is a white powder. dH (250 MHz, DMSO-
d6): 4.10 (s, 6H). dC (62.5 MHz, DMSO-d6): 172.7 (2C, carbonyl), 55.8
(2C, quaternary), 46.3 (6C, CH).
ꢀ
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hydroxide solution (0.052 mmol), made from deionized (conduc-
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argon, and heated to 135 ꢁC for 3 h. After acidification with a slight
excess of dilute hydrochloric acid, the solvent was evaporated, and
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product of the solvent-induced rearrangement of cubane diacid 6.
Pale brown powder. dH (250 MHz, DMSO-d6): 3.05e2.98 (m, 4H),
2.94 (m, 2H). dC (62.5 MHz, DMSO-d6): 176.8 (2C, carbonyl), 48.8,
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ꢀ
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