A new OsO4-mediated carbon-carbon bond cleavage reaction leading to the formation of anthraquinone

Article abstract of DOI:10.1246/cl.2001.48

A new OsO₄-mediated carbon-carbon bond cleavage reaction leading to the formation of anthraquinone was observed. The reaction goes through the dihydroxylated intermediate and is aided by the presence of pyridine.

Full text of DOI:10.1246/cl.2001.48

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Chemistry Letters 2001
A New OsO -Mediated Carbon–Carbon Bond Cleavage Reaction
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Leading to the Formation of Anthraquinone
Shouhai Gao, Wei Wang, and Binghe Wang*
Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, U.S.A.
(Received September 20, 2000; CL-000872)
A new OsO -mediated carbon–carbon bond cleavage reaction
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leading to the formation of anthraquinone was observed. The reac-
tion goes through the dihydroxylated intermediate and is aided by
the presence of pyridine.
Osmium tetroxide (OsO ) is widely used for the cis-dihydrox-
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ylation of alkenes.1 Herein, we report an unusual carbon–carbon
,2
bond cleavage reaction mediated by OsO resulting in the forma-
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tion of anthraquinone.
When 9-vinylanthracene (1) was treated with 3 equivalents of
trimethylamine N-oxide (TMO) in the presence of catalytic amount
of OsO (5%) at 65 °C, anthraquinone (3) was obtained in 39%
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yield together with the expected diol (2) in a 5:1 ratio (Scheme 1).
Apparently, the reaction leading to the formation of anthraquinone
involves a carbon–carbon bond cleavage. Such a carbon–carbon
bond cleavage reaction is unusual. Aimed at achieving a better
understanding of the reaction pathway, we also subjected the diol
and about 43% of the starting material was recovered (Table 1),
which was the reason for the somewhat low yield of
anthraquinone. Similar results were observed with the oxidation of
9-(1-hydroxyethyl)anthracene (5, Scheme 2) under the same condi-
(2) to the same reaction conditions and found that the diol (2) was
tions (Entry 4, Table 1).
To further examine the role of the hydroxy group in this oxi-
dation reaction, 9-anthraldehyde (6), 9-(methoxymethyl)-
converted to anthraquinone completely indicating that the diol (2)
was probably the intermediate for the formation of anthraquinone.
anthracene, and 9-acetylanthracene, which all lack the hydroxy
group at the benzylic position, were subjected to the same reaction
conditions and it was found that none of them was converted to
anthraquinone. Such results further indicate that a hydroxy group
was essential for this type of cleavage reaction. It is interesting to
note that there are literature reports that anthracene and its certain
derivatives can be transformed into anthraquinone via a photo-
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chemical process in the presence of OsO . However, such photo-
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5
chemical reactions could not cleave carbon–carbon bonds. This is
Because hydroxy groups are known to be able to coordinate
to osmium,3 it was thought that the hydroxy group probably
plays a critical role in this reaction leading to the carbon–carbon
bond cleavage. This was confirmed with the experiment using
anthracene and 9-methylanthracene, which lack the hydroxy
group and were not affected when subjected to the same reaction
conditions. In contrast, 9-(hydroxymethyl)anthracene (4, Scheme
,4
in direct contrast to the reactions under study, which involves a
carbon–carbon bond cleavage leading to the formation of
anthraquinone. Aimed at examining the effect of light on the reac-
tions under study, we conducted the OsO4
-
mediated oxidation of 4
in the dark and found that the same results were obtained as com-
pared to the reactions without shielding the reaction flask away
from normal daylight (Entry 6, Table 1). Furthermore, anthracene
itself was not converted to anthraquinone under our experimental
conditions. Therefore, we conclude that the reactions under study
are not a light driven process and the reaction mechanism is also
different from that reported in a photochemical process.
To understand the role of TMO in this reaction, we also stud-
ied the reaction without added TMO using stoichiometric amount of
OsO . Similar to the reaction in the presence of TMO, 4 underwent
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) was converted to anthraquinone under the same conditions in
over 30% yield with the formation of 9-anthraldehyde (6) (10%)
Entry 2, Table 1). Therefore, the oxidation of 4 could take on
(
two different pathways, one involving carbon–carbon bond
cleavage and the other one involving the simple oxidation of
the alcohol to give the aldehyde. It needs to be noted that with
3
equivalents of TMO, the reaction did not proceed to completion
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both the carbon–carbon bond cleavage reaction and simple oxida-
tion, leading to the formation of 3 and 6, respectively. However,
the ratio between 3 and 6 was much lower (1:2.7) than that of the
reaction in the presence of 3.0 equivalents of TMO (2.1:1) (Entries
2
and 3, Table 1). This indicates that the presence of TMO does
play a role, which is more than to regenerate OsO . The situation
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with the oxidation of 5 is similar (Entries 4 and 5, Table 1).
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
49
Ligand coordination to OsO is known to affect its reactivi-
ther oxidation mediated by OsO to give other degradation prod-
ucts. The fact that the starting material disappeared implies that the
oxidation reaction indeed occurred with styrene.
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ty.6–8 We suspect that the coordination of TMO or its reduced
form, trimethylamine, to OsO might be the reason for the different
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outcome of the reactions with and without added TMO. Therefore,
we were interested in studying the effect of added amines on the
product distribution in the oxidation of 4 (Table 2). We chose to
study the effect of pyridine and triethylamine (TEA) as model
amines. In one set of studies, we changed the amount of pyridine
added to the reaction mixture. In the absence of pyridine (Entry 2,
In a typical experiment, to a suspension of 4 (164 mg, 0.787
mmol) and TMO (262 mg, 2.36 mmol, 3.0 equiv) in THF (5 mL)
and pyridine (0.1 mL) was added the solution of OsO (10 mg,
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0.039 mmol, 5% equiv) in water (1 mL). The reaction mixture was
stirred at 65 °C under nitrogen for 24 h. After cooled to room tem-
perature, a 10% aqueous solution of sodium hydrosulfite (10 mL)
was added and the mixture was stirred for 10 min. After extraction
with EtOAc (3 × 50 mL), the combined organic layers was dried
Table 2), catalytic amount of OsO in the presence of 3.0 equiva-
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lents of TMO was able to give both 3 and 6 in a ratio of 1:2.5.
This ratio was much lower than that (2.1:1) of the reaction when
pyridine was added to the reaction mixture in a ratio of 5:1:0.1 for
THF, water, and pyridine (Entry 1, Table 2). When a higher con-
centration of pyridine was used (Entry 3, Table 2), the product
ratio between 3 and 6 was over 10:1. These results clearly indicate
that pyridine plays an important role in determining the product
distribution. The higher the pyridine concentration, the higher ratio
of anthraquinone over aldehyde was observed. However, the addi-
tion of TEA to the reaction mixture resulted in a higher ratio of
anthraldehyde in the product distribution (Entries 8 and 9, 3 and
over anhydrous MgSO . The final product was obtained from silica
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gel column chromatography using a mixture of ethyl acetate and
hexanes.
In conclusion, 9-(1-hydroxyalkyl)anthracene can be converted
to anthraquinone using TMO as the oxidant in the presence of cat-
alytic amount of OsO with the best yield in the range of 60–70%.
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The hydroxy group is essential for this reaction. The presence of
pyridine favors the formation of the anthraquinone product, while
the presence of TEA favors the simple oxidation of the starting
alcohols to the corresponding aldehydes. Such reactions can be
used for the preparation of biologically important anthraquinone
10, Table 2), which indicates that the effect of TEA is opposite to
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that of pyridine in such reactions.
compounds and will also be very useful in analyzing functional
As described earlier, the reaction was not 100% complete
when 3 equivalents of TMO was used in the presence of catalytic
group compatibilities in designing reactions involving OsO4.
amount of OsO . On the other hand, a large excess of TMO could
We acknowledge the financial support of the National
Institutes of Health (DK55062). We also thank Professor Daniel
Comins for helpful discussions.
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drive the reaction to completion when a lower ratio of pyridine was
used (Entries 4 and 5, Table 2). However, it is interesting that in the
presence of a higher concentration of pyridine, the reaction did not
proceed to the completion even with 20 equivalents of TMO
References and Notes
1
2
M. Schroder, Chem. Rev., 80, 187 (1980).
(
Entries 6 and 7, Table 2). We suspect that the different effects
observed with pyridine and TEA were most likely due to their coor-
dination to osmium, which modified the reactivity of OsO . Similar
H. C. Kolb, M. S. VanNieuwenhze, and K. B. Sharpless, Chem. Rev.,
9
4, 2483 (1994).
3
4
T. J. Donohoe, N. J. Newcombe, and M. J. Waring, Tetrahedron
Lett., 40, 6881 (1999).
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6–8
effects are certainly well documented in the literature. However,
proving such a mechanism is beyond the scope of this study.
To examine whether the same type of reactions occurs with
other vinyl aromatic compounds, we also examined the oxidation of
T. J. Donohoe, R. Garg, and P. R. Moore, Tetrahedron Lett., 37,
3
407 (1996).
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J. M. Wallis and J. K. Kochi, J. Am. Chem. Soc., 110, 8207 (1988).
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styrene using TMO in the presence of OsO in a mixture of
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THF–H O–pyridine (5:1:0.1). Complete disappearance of the start-
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ing material was observed at the end of the reaction. However, no
benzoquinone was observed, which is understandable. If quinone is
formed upon the oxidation of styrene following the same pathway
as the oxidation of vinylanthracene, the double bonds of the
quinone product are not expected to be stable and can undergo fur-
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