Fast and mild palladium(II)-catalyzed 1,4-oxidation of 1,3-dienes via activation of molecular oxygen with a designed cobalt(II) porphyrin

Article abstract of DOI:10.1039/b417758d

The use of a Co(porphyrin)-amide ligand, 2, in the palladium(II)-catalyzed 1,4-diacetoxylation of conjugated dienes under O₂ results in aerobic oxidation. The catalyst was highly active under O₂, and the 1,4-diacetoxylation reaction

Full text of DOI:10.1039/b417758d

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Fast and mild palladium(II)-catalyzed 1,4-oxidation of 1,3-dienes via
activation of molecular oxygen with a designed cobalt(II) porphyrin{
Renzo C. Verboom, Vincent F. Slagt and Jan-E. Ba¨ckvall*
Received (in Cambridge, UK) 25th November 2004, Accepted 21st December 2004
First published as an Advance Article on the web 21st January 2005
DOI: 10.1039/b417758d
palladium(II)-catalyzed oxidations and aromatized starting mate-
rial was found to be the major side-product.
The use of
a Co(porphyrin)-amide ligand, 2, in the
palladium(II)-catalyzed 1,4-diacetoxylation of conjugated dienes
under O2 results in aerobic oxidation. The catalyst was highly
active under O2, and the 1,4-diacetoxylation reaction could also
be performed under air.
Inspired by recent reports on direct oxygen activation in
Pd(II)-catalyzed aerobic oxidation reactions,5 we decided to further
investigate the design of Co(porphyrin) complexes as co-catalysts
for efficient palladium-catalyzed aerobic oxidations. We expected
that an electron-donating amide ligand attached to the metallo
porphyrin would favor coordination to palladium. This would
ensure palladium coordination in the near proximity of the oxygen
activating metallo porphyrin, probably leading to a more active
catalyst and hence improved yields. It is known that amides form
strong complexes with Pd(II),6 and the compatibility of amide
ligands with 1,4-oxidation has already been demonstrated in
asymmetric 1,4-oxidation reactions.7 Herein we report the
application of the novel complex 2, in which a cobalt(II) porphyrin
functionalized with an amide ligand, is used as an oxygen-
activating agent (Fig. 1).
Palladium(II)-catalyzed 1,4-oxidation is a useful synthetic method
for the oxidation of conjugated dienes.1 A wide range of
nucleophiles can be added across the diene with high regio- and
stereoselectivity. A biomimetic aerobic variant of this 1,4-
diacetoxylation was developed by the use of a one-pot triple
catalytic system, employing a metal macrocyclic complex of a
porphyrin, a phthalocyanine or a salene derivative as oxygen
activating agents.2 The overall process results in a net oxidation of
the diene by molecular oxygen via three consecutive electron
transfer steps in a triple catalytic process (Scheme 1).
The efficiency of this process was improved by the use of a
bifunctional cobalt[tetrakis(hydroquinone)porphyrin], Co(TQP),
which acts as both an oxygen activating agent and electron
transfer mediator.3 Interestingly, with the corresponding hydro-
quinone-protected Co[meso-tetra(2,5-dimethoxyphenyl)porphyrin]
Co(TDMPP), the reaction proceeded even in the absence of
quinone as an electron transfer mediator, and a mechanism
involving a direct electron transfer from palladium to the oxidized
metallo macrocycle was proposed.4 The Co(porphyrin) derivative
with a methoxy group only in the 2-position (Co(2-TMMPP))
showed similar activity. A drawback is that in most cases
only poor to moderate yields were obtained for these aerobic
The porphyrin was employed in the aerobic 1,4-diacetoxylation
reaction of 1,3-cyclohexadiene with 2.5 mol% Pd(OAc)2 and
2.75 mol% of Co(porphyrin)-amide 2. The reaction was performed
on a 1 mmol scale using a gas buret filled with oxygen to
simultaneously measure the oxygen uptake.8 The rate of the
oxygen consumption was initially very fast (6 mL in 20 min;
y50% conversion), but decreased rapidly when a significant
amount of palladium black was observed. After full conversion,
1 was isolated in 19% yield (Table 1, entry 1). Addition of LiOAc
improved the yield and no precipitation of palladium black was
observed (entries 2–5). The reaction is slightly slower with LiOAc
and the rate depends on the concentration of LiOAc. Product
formation was highest at 0.15 M acetate concentration and 1 was
obtained in 46% yield.9 When this reaction was repeated with a
higher catalyst loading (5 mol% Pd(OAc)2) the yield was improved
to 68% (entry 6). The relative stereochemistry of the product 1 was
also dependent on the acetate concentration. Addition of small
Scheme 1 The triple catalytic system and the overall reaction of the
diacetoxylation. MLm 5 metal macrocyclic complex.
{ Electronic supplementary information (ESI) available: synthesis and
characterization of complex 2 and detailed experimental data. See http://
www.rsc.org/suppdata/cc/b4/b417758d/
Fig. 1 Cobalt(II) porphyrin 2.
*jeb@organ.su.se
1282 | Chem. Commun., 2005, 1282–1284
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Table 1 Aerobic 1,4-diacetoxylation of 1,3-cyclohexadienea
Entry Ligand
Oxidant LiOAc (M) Yield (%)b Trans–cisc
on the cobalt(II) porphyrin, as demonstrated by the improved
yields in the presence of acetate.9 The previously reported aerobic
reactions using Co(TDMPP) and Co(2-TMMPP) were run in the
absence of LiOAc and under oxygen. Concluding from our results
with complex 2 as presented here, we believe that decomposition of
the active complexes in those reactions can be one of the
explanations for the lower yields. The absence of an extra amide
ligand attached to the porphyrin for the coordination to Pd(II) can
also have an effect on the yield.
1
2
3
4
2
2
2
2
2
2
2
2
2
O2
O2
O2
O2
O2
O2
O2
Air
Air
—
19
21
46
37
31
68
32
28
54
0
35 : 65
49 : 51
47 : 53
43 : 57
35 : 65
45 : 55
83 : 17
29 : 71
40 : 60
—
0.05
0.15
0.3
5
0.6
6d
7e
8
0.15
0.15
—
0.15
—
The high activity of the Co(porphyrin)-amide complex under
oxygen encouraged us to run the 1,4-oxidation reaction under air.
Surprisingly, in the absence of LiOAc, 1 was obtained in higher
yield (28%) than in the reaction performed under oxygen (entry 8).
The change in color of the solution during the reaction (from dark
red to dark green) and precipitation of palladium black shows that
also under these conditions the complex is not completely stable.
The addition of LiOAc (0.15 M) had a beneficial effect on the
reaction, and 1 could be isolated in 54% (entry 9). The reaction
under air is thus higher yielding than the reaction under molecular
oxygen and with the same catalyst load, and we showed for the
first time that the 1,4-oxidation reaction can effectively be run
under air.
9
10f
a
Co(TPP) O2
All reactions were performed on a 1.0 mmol scale. Reaction
solution of Pd(OAc)2
(2.5 mol%), 2 (2.75 mol%) and LiOAc (if required) in 2 mL HOAc.
conditions: the diene was added to
a
The reaction mixture was stirred at rt under an oxygen atmosphere
for 16 h. Isolated yields of 1,4-diacetoxy-2-cyclohexene. Deter-
b
c
d
e
mined by 1H NMR. With 5 mol% Pd(OAc)2 and 5.5 mol% 2. In
2 mL CH2Cl2–HOAc 5 : 1. With 2.5 mol% Co(TPP).
f
amounts of LiOAc (0.05 M) decreased the cis-selectivity from 65 to
51%. Addition of more LiOAc led to a recovery of the cis-
selectivity and at LiOAc concentrations of 0.6 M or higher, 1 was
obtained with 65% cis-selectivity. The stereoselectivity could be
altered by the use of co-solvents and a reaction in CH2Cl2–
HOAc 5 5 : 1 resulted in 83% trans-selectivity (entry 7). However,
with all solvent mixtures, lower yields were obtained than with
neat acetic acid.
The rates of the reactions with Co(porphyrin) 2 with different
concentrations of LiOAc are shown in Fig. 3. A comparison of the
rates with 2 with the rate of the corresponding reaction employing
2.5 mol% Co(TPP) and 10 mol% hydroquinone showed that the
reaction catalyzed by ligand 2 in the presence of acetate
concentrations up to 0.6 M was considerably faster than the
Co(TPP)–quinone system. The intramolecular electron transfer
from palladium to the oxidized metal-macrocycle is therefore
more efficient than in the intermolecular electron transfer via
p-benzoquinone. Moreover, a control experiment with Co(TPP)
but without p-benzoquinone gave no product, which shows that
coordination of the porphyrin to palladium is essential for the
oxidation reaction (entry 10).
From the fast conversion of the diene with complex 2 in the
absence of LiOAc, it seems that the oxygen complex of 2 is a very
powerful oxidant. However, with a 19% yield of 1, the reaction
resulted mainly in the formation of benzene, a product formed by
decomposition of the intermediate (p-allyl)palladium complex. The
improved yields in the presence of LiOAc suggest a stabilizing
effect of acetate on either the Pd(II) intermediate or the
Co(porphyrin). It is believed that the electron transfer takes place
directly from the palladium to the oxidized cobalt metal center
(Fig. 2). Since the rate of the reaction decreases at higher
concentrations of LiOAc, it seems likely that acetate coordinates to
the cobalt metal center in the porphyrin and thus competes
with coordination of oxygen. Less cobalt-bonded oxygen
would then result in a slower reaction. UV–vis spectroscopy
titrations in acetic acid revealed the binding of acetate to the
(Co)porphyrin 2 complex with corresponding binding constants
of K1 5 2.2 6 103 M21 and K2 5 1.0 6 104 M21. These results
confirm that coordination of acetate to cobalt indeed takes place.
Noteworthy is that the addition of acetate has a stabilizing effect
We also studied the effect of the chiral center in complex 2 on the
asymmetric induction in the 1,4-oxidation reaction. Unfortunately,
under the present reaction conditions there was essentially no
asymmetric induction.
Fig. 3 Plot of the oxygen uptake against time in the aerobic 1,4-
Fig. 2
oxidation of 1 mmol of 1,3-cyclohexadiene.
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4 H. Grennberg and J.-E. Ba¨ckvall, J. Chem. Soc., Chem. Commun., 1993,
1331.
In conclusion, we have shown that aerobic 1,4-diacetoxylation
reactions can be run under an oxygen atmosphere as well as under
air using complex 2. The diacetate was obtained in yields up to
68% at ambient temperature.
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We thank the Swedish Research Council and the Netherlands
Organization for Scientific Research (NWO) for financial support.
Renzo C. Verboom, Vincent F. Slagt and Jan-E. Ba¨ckvall*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm
University, SE-106 91 Stockholm, Sweden. E-mail: jeb@organ.su.se;
Fax: +46 8 154908; Tel: +46 8 6747178
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Notes and references
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8 The oxygen consumption gives an indication of the progress of
the reaction: 12 mL O2 corresponds to the conversion of 1 mmol of
diene.
1 J.-E. Ba¨ckvall, Palladium-Catalyzed 1,4-Additions to Conjugated Dienes,.
Review in Metal-catalyzed Cross Coupling Reactions, ed. A. de Meijere
and F. Diederich, Wiley-VCH, Weinheim, 2004, pp. 479–529.
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3 H. Grennberg, S. Faizon and J.-E. Ba¨ckvall, Angew. Chem., Int. Ed.
Engl., 1993, 32, 263.
9 After completion of the reaction the (Co)porphyrin-amide 2 could be
recovered.
1284 | Chem. Commun., 2005, 1282–1284
This journal is ß The Royal Society of Chemistry 2005