Manganese catalyzed cis-dihydroxylation of electron deficient alkenes with H2O2

Article abstract of DOI:10.1039/c0ob00102c

A practical method for the multigram scale selective cis-dihydroxylation of electron deficient alkenes such as diethyl fumarate and N-alkyl and N-aryl-maleimides using H₂O₂ is described. High turnovers (>1000) can be achieved with this efficient manganese based catalyst system, prepared in situ from a manganese salt, pyridine-2-carboxylic acid, a ketone and a base, under ambient conditions. Under optimized conditions, for diethyl fumarate at least 1000 turnovers could be achieved with only 1.5 equiv. of H₂O₂ with d/l-diethyl tartrate (cis-diol product) as the sole product. For electron rich alkenes, such as cis-cyclooctene, this catalyst provides for efficient epoxidation.

Full text of DOI:10.1039/c0ob00102c

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Manganese catalyzed cis-dihydroxylation of electron deficient alkenes with
H2O2†
Pattama Saisaha,a Dirk Pijper,a Ruben P. van Summeren,b Rob Hoen,a Christian Smit,a Johannes W. de Boer,c
Ronald Hage,c Paul L. Alsters,b Ben L. Feringaa and Wesley R. Browne*a
Received 10th May 2010, Accepted 25th June 2010
DOI: 10.1039/c0ob00102c
A practical method for the multigram scale selective cis-dihydroxylation of electron deficient alkenes
such as diethyl fumarate and N-alkyl and N-aryl-maleimides using H2O2 is described. High turnovers
(>1000) can be achieved with this efficient manganese based catalyst system, prepared in situ from a
manganese salt, pyridine-2-carboxylic acid, a ketone and a base, under ambient conditions. Under
optimized conditions, for diethyl fumarate at least 1000 turnovers could be achieved with only
1.5 equiv. of H2O2 with d/l-diethyl tartrate (cis-diol product) as the sole product. For electron rich
alkenes, such as cis-cyclooctene, this catalyst provides for efficient epoxidation.
cyclooctene and near complete atom efficiency in the oxidant
H2O2. By contrast, this system shows little activity with electron
deficient alkenes such as diethyl fumarate.
A key challenge, therefore, is to develop readily accessible
Introduction
The selective and atom efficient cis-dihydroxylation of alkenes
is a key transformation in synthetic organic chemistry,1 with
contemporary methods relying predominantly on stoichiometric
oxidants, such as MnO4 and OsO4,1c,2 or transition metal based
methods based on simple catalysts, preferably prepared in situ,
-
that are able to achieve similar efficiency in the cis-dihydroxylation
oxidation catalysts, in particular, ruthenium,3,4 and osmium (asym-
for electron deficient alkenes.
metric) dihydroxylation methods.5
Practical osmium free methods for cis-dihydroxylation of
alkenes that avoid the need for excess amounts of oxidant are
highly desirable, both in synthesis and for the large scale produc-
In the present contribution we describe a readily accessible
catalytic system based on manganese and H2O2 that is highly
selective in the cis-dihydroxylation of electron deficient alkenes
such as diethyl fumarate and N-alkyl-maleimides on a multigram
tion of important building blocks, not least N-aryl and N-alkyl-
scale (Scheme 1).
maleimides.6 Furthermore, the cis-dihydroxylation of electron
deficient alkenes such as N-alkyl-pyrrole-2,5-diones remains a
major challenge with the more reactive ruthenium based catalysts
systems employing NaIO4 providing one of the few effective
routes available to the cis-diol products. For example 1-benzyl-
1H-pyrrole-2,5-dione can be converetd to (meso)-N-benzyl-3,4-
dihydroxy-2,5-pyrrolidinedione using 1.3 equiv. of NaIO4 and 0.8
mol% of RuIIICl3 in 73.3% yield.6
Scheme 1 cis-Dihydroxylation of 1-benzyl-1H-pyrrole-2,5-dione using
the method described here.
In recent years, considerable advances have been made in
the development of atom-efficient and environmentally friendly
catalytic cis-dihydroxylation methods employing H2O2,1 most
The present system is based on a manganese source in combina-
notably, in the use of iron pyridyl-amine complexes, by Que
tion with pyridine-2-carboxylic acid, a ketone and a base. With this
et al.,7 manganese complexes by De Vos et al.8 and Feringa
method electron deficient alkenes can be converted quantitatively
et al.9 and others10 and ruthenium complexes by Che et al.11
to the corresponding cis-dihydroxylation products. Furthermore,
we show that for electron rich alkenes epoxidation dominates
with the ratio between cis-diol and epoxide products showing a
qualitative correlation between electron deficiency and the product
distribution observed.
With the [MnIII2O(RCO2)2(tmtacn)2]2+ catalysts12 we have reported
recently,9b–e the cis-dihydroxylation of electron rich cis-alkenes was
achieved with over 8000 turnovers to the cis-diol product of cis-
aStratingh Institute for Chemistry, Faculty of Mathematics and Natural
Sciences, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The
Netherlands. E-mail: w.r.browne@rug.nl; Fax: +31 50 363 4296; Tel: +31
50 363 4428
Results and discussion
bDSM Innovative Synthesis, PO Box 18, 6160 MD Geleen, The Netherlands
cis-Dihydroxylation of electron deficient alkenes
cRahu Catalytics BV, BioPartner Center Leiden, Wassenaarseweg 72, 2333,
AL Leiden, The Netherlands
The catalyst is formed in situ by addition of a MnII salt and
pyridine-2-carboxylic acid to acetone followed by addition of the
substrate and then NaOAc (aq). The reaction mixture is then
† Electronic supplementary information (ESI) available: Full details for
reactions in Tables 1 and 2 with characterisation and spectra. See DOI:
10.1039/c0ob00102c
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Table 1 cis-Dihydroxylation of alkenes by MnII(ClO4)2/pyridine-2-
(see for example section 6 of the ESI†) and 1H NMR spectroscopy
to determine product ratios. Isolation of cis-diol products was
carried out using standard synthetic procedures (see ESI for
detailed procedures). The optimum reaction conditions were
found to be substrate specific but in general a 1 : 6 : 10 mixture
of a MnII salt, pyridine-2-carboxylic acid and NaOAc provided
good conversion and yield of the cis-diol products.
The present system is equally effective for mono-, di-, tri- and
tetra-substituted electron deficient alkenes. For alkenes such as
ethyl crotonate (Table 1, entries 10–12) low conversion and selec-
tivity between cis-diol and epoxide products was observed. How-
ever overall good to excellent conversion was achieved with elec-
tron deficient trans-alkenes, such as diethyl fumarate and diethyl-
2-methyl-fumarate, and cyclic cis-alkenes such as maleimide.
The reduced reactivity towards diethyl maleate and N,N¢-
dibutylmalediamide is surprising considering the fact that, e.g.,
maleimide can be converted to the corresponding cis-diol product
quantitatively (Table 1). Lowering the substrate concentration
provided a modest improvement in conversion for diethyl maleate
however a maximum conversion of only 63% was achieved in the
present study.
carboxylic acid/NaOAc/H2O2 in acetone
Substrate
Conversion (%)a Isolated yield (%)
1
2
100(>95%)b
>95
91(95)b
88
3
4
63
47c
98
100
5
6
100
100
>95
91
For diethyl fumarate and diethyl maleate a difference in maxi-
mum conversion (Table 1) and reaction rate was notable. Diethyl
fumarate can be converted quantitatively to the d/l-diethyl tartrate
within 60 min under optimised reaction conditions. For diethyl
maleate by contrast only 20–30% conversion over several hours
can be achieved using these conditions. In order to investigate
the origin of these differences further a competition experiment
in which a 1 : 1 mixture of diethyl fumarate and diethyl maleate
was oxidised under conditions optimised for diethyl fumarate was
performed (see Fig. 1 and ESI†). Under these conditions the
conversion of diethyl maleate was 20% as expected. Surprisingly
however only 90% conversion was achieved for diethyl fumarate
(in the absence of diethyl maleate full conversion is achieved
under these conditions). The fact that substantial conversion was
7
100
75
8
9
55
81
32
55a,d
10
11
12
<10
<10
<10
cis-diol:epoxidea 2 : 1
cis-diol:epoxidea 1 : 1
cis-diol:epoxidea 1 : 1
a Determined by Raman spectroscopy using the C C stretching band at
ca. 1600 cm-1 and by 1H NMR spectroscopy. For detailed conditions and
procedures see ESI. b In 2-butanone. c 25% and d 19% recovered starting
material.
cooled in ice water and H2O2 is added either as a single batch or by
syringe pump. Under optimized conditions, for diethyl fumarate at
least 1000 turnovers could be achieved with only 1.5 equiv. of H2O2
with d/l-diethyl tartrate (cis-diol product) as the sole product.13
Further oxidation of the cis-diol formed was not observed, even
with excess H2O2.
A series of electron deficient alkenes together with conversions
and isolated yields are shown in Table 1. The reaction conditions
were optimized for each of the electron deficient alkenes examined
using Raman spectroscopy to monitor conversion of the alkene
Fig. 1 1H NMR spectrum of reaction mixture (diluted in CDCl3).
Reaction conditions: Mn(ClO4)2·6H2O (1.0 mmol), pyridine-2-carboxylic
acid (3.0 mmol), NaOAc (30.0 mmol), 1,2 dichlorobenzene (as internal
standard, 0.5 mmol), diethyl fumarate (0.5 mmol) and diethyl maleate
(0.5 mmol) in acetone at 5 ◦C with single addition of H2O2 (1.5 equiv.).
For Raman spectra and the full NMR spectrum see ESI. Diethylfumarate
(6.8 ppm), diethylmaleate (6.2 ppm), d/l-diethyltartrate (4.52 ppm),
meso-diethyltartrate (4.55 ppm).
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workers for FeII polypyridyl based catalysts.15 This may indicate
that selectivity is substrate, and not catalyst, controlled.
Table 2 cis-Dihydroxylation and epoxidation of electron rich alkenes by
MnII(ClO4)2/pyridine-2-carboxylic acid/NaOAc/H2O2 in acetone
Substrate
Conversion (%)a Yield
Catalyst composition
1
2
cis-cyclooctene
97
12% cis-diol (12%)b
72% epoxide (60%)b
12 a-hydroxy ketone (10%)b
2% cis-diol
The catalyst system is sensitive to changes in catalyst composition.
With picolinic-2-carboxaldehyde, which can be oxidized in situ
(Scheme 2, see also ESI†), full conversion is observed
cyclohexene
100
54% epoxide
14% a-hydroxy ketone
3% cyclohexenone
8% cis-diol
3
4
5
6
1-methyl-
cyclohexene
100
82
64% epoxide
9% cis-diol
35% epoxide
18% a-hydroxy ketone
4% cis-diol
75% epoxide
9% other
7% cis-diol
1-octene
styrene
Scheme 2 Oxidation of pyridine-2-carboxaldehyde.
100
100
With other substituted pyridine carboxylic acids, e.g. pyridine-
2,5-dicarboxylic acid, full activity was observed (Table 3). By
contrast, for picolinic acid N-oxide or pyridine 2,6-dicarboxylic
acid, activity was not observed (Table 3). This indicates that the
co-catalyst is acting as a ligand to the MnII and that the N-oxide,
trans-b-
methylstyrene
65% epoxide
12% a-hydroxy ketone
7
2-methyl-2-pentene 100
13% cis-diol
62% epoxide
Table 3 Effect of molecular structure of the pyridyl ligand on efficiency
towards the cis-dihydroxylation of diethyl fumarate
a Determined by Raman spectroscopy and by 1H NMR spectroscopy.
For detailed conditions and procedures see ESI. b Isolated yields in
parentheses.
Conversion
(%)
Conversion
(%)
Ligand
Ligand
achieved for both substrates confirms that catalyst inhibition by
the substrates does not occur. Hence it is apparent that product
inhibition (either from oxidation or hydrolysis products) of the
diethylmaleate may be involved.14 The stability of the substrate
and products towards hydrolysis under the reaction conditions
employed indicates that it is oxidation products which cause
catalyst inhibition.
To investigate the possibility of primary oxidation products (i.e.
meso- and d/l-diethyl-tartrate) being responsible for product in-
hibition, similar experiments were performed using a 1 : 1 mixture
of diethyl fumarate and either meso or d/l-diethyl tartrate. In both
cases full conversion of the diethyl fumarate was achieved. This
confirms that the primary oxidation products are not responsible
for catalyst inhibition.
A
A
0
B
C
0
100
100
A
B
0
D
B
100
100
0
cis-Dihydroxylation and epoxidation of electron rich alkenes
D
D
D
0
D
D
0
A series of electron rich alkenes is shown in Table 2. For all
substrates examined the main product observed is the epoxide
product. However, significant amounts of diol were formed in all
cases. As has been noted for the RuCl3/NaIO43,6 and RuIIItmtacn11
systems, and to a lesser extent the Mn-tmtacn systems,9 the diol
produced is readily oxidised further to the a-hydroxy ketone
and ultimately to C–C bond cleavage. The propensity for further
oxidation of the cis-diol products results in reduced selectivity.
Nevertheless, epoxidation was observed as the primary product
in most cases, especially for electron rich alkenes such as cis-
cyclooctene and styrene (Table 2, entries 1 and 5). Overall the
substrate scope shows a qualitative correspondence between the
cis-diol/epoxide ratio with the electron deficiency of the substrate.
The extent of epoxidation of alkenes such as cis-cyclooctene (1 : 6
diol/epoxide) and ethyl crotonate (2 : 1 diol/epoxide) (see Tables
1 and 2) is comparable to the trends observed by Que and co-
0
80
100
All reactions carried out in acetone at room temperature. Reaction
conditions (Mn/ligand/NaOAc/H2O2, mol%): A: (0.1/0.1/1.2/400), B:
(0.1/0.3/1.0/200). C: (0.1/0.3/1.2/800). D: (0.1/0.3/1.0/800). The oxi-
dation of diethyl fumarate was monitored by following the intensity of the
1665 and 1648 cm-1 Raman bands (alkene stretching vibration), relative to
the internal standard 1,2-dichlorobenzene (1575 cm-1).
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Table 4 Conversion of the diethyl fumarate with various bases and acid
Table 6 cis-Dihydroxylation of diethyl fumarate in acetonitrile with
various ketones
Base or acid
Mol (%)
Conversion (%)
Ketone
Amount
Conversion (%)
none
—
0
NaOAc
KOAc
1.0
1.0
20.0
1.0
1.0
1.0
1.0
1.0
100
100
100
100
100
100
70
none
—
0
20
0
CH3COCH3
CH3COCH3
CF3COCH3
CF3COCH3
CF3COCH3
CF3COCH3
CF3COCH3
CF3COCF3
CF3COCH3 (in MTBE)
CCl3COCCl3
10 vol (%)
0.3 equiv.
30 vol (%)
20 vol (%)
10 vol (%)
5 vol (%)
0.3 equiv
10 vol (%)
10 vol (%)
10 vol (%)
NaOAc
NaOH
NaHCO3
Na2CO3
NH4OAc
AcOHa
100
>95
>95
>95
90
0
>95
0
0
The oxidation of diethyl fumarate was monitored by following the intensity
of the 1665 and 1648 cm-1 bands (alkene stretching vibration). Relative to
the internal standard 1,2-dichlorobenzene (1575 cm-1).a Confirmed by 1H
NMR spectroscopy.
The oxidation of diethyl fumarate was monitored by following the intensity
of the 1665 and 1648 cm-1 bands (alkene stretching vibration) relative to
the internal standard 1,2-dichlorobenzene (1575 cm-1). In all cases d/l-
diethyl-tartrate was the sole product observed.
Table 5 Effect of variation in equivalents of base on reactivity of the
present system under conditions where the ratio of MnII to pyridine-2-
carboxylic acid is 1 : 1
Notably when a 1 : 1 ratio of pyridine-2-carboxylic acid/MnII is
employed (Table 5) the system is highly sensitive to the number of
equivalents of base added with a 1 : 1 ratio being optimum. This
indicates that the base serves mainly to deprotonate pyridine-2-
carboxylic acid and allows the catalyst to form. For the pyridine
based ligands (Table 3) that do not bear a carboxylic acid residue,
the addition of base is still necessary to ensure the deprotonation
of the pyridine in the acetone/water mixture and furthermore
is required in order to achieve a significant reaction rate and
conversion.
By contrast, in the absence of added base or where acid, e.g.,
acetic acid, is added prior to addition of H2O2, conversion was not
observed (Table 4). However, once the reaction had commenced
addition of acetic acid resulted in a decrease in reaction rate and
conversion but did not inhibit the reaction fully (see ESI†).
Mol% of NaOAc
Conversion (%)
0
0
0
22
32
46
72
31
0.1
0.2
0.3
0.5
1.0
2.0
The oxidation of diethyl fumarate was monitored by following the intensity
of the 1665 and 1648 cm-1 bands (alkene stretching vibration). Relative to
the internal standard 1,2-dichlorobenzene (1575 cm-1).
Solvent dependence
although it can be formed under reaction conditions (Scheme 1),
is not involved in the oxidation catalysis. A notable observation is
that for quinoline-8-carboxylic acid no conversion was observed in
contrast to quinoline-8-carbaldehyde for which 80% was observed.
In this case the very limited solubility of the quinoline-8-carboxylic
acid in the reaction mixture is almost certainly the reason for the
difference in reactivity, emphasising the point that the conversion
achieved is highly dependent on the initial formulation of the
reaction mixture.
The system is relatively insensitive to the nature of the base
employed with, e.g., NaOAc, NaHCO3 and NaOH or Mn(OAc)2
providing comparable results (Table 4). The insensitivity in terms
of activity or selectivity to variation in the base employed
indicates that the catalyst is not dependent on acetate as a ligand.
Furthermore, the number of equivalents of base employed does
not affect the reaction significantly provided that it is in excess
with respect to the pyridine-2-carboxylic acid and MnII.
Acetone is the solvent of choice in the present study. However, the
catalysis proceeded equally well in 2-butanone (Table 1, entry 1).
Initial screening of the reaction conditions for solvent tolerance
indicated that activity is observed only in ketone based solvents.
Notably, the system is tolerant to some co-solvents (Table 6),
for example in acetonitrile 20% conversion was obtained with
10 vol% acetone. Furthermore, electron deficient ketones such as
1,1,1-trifluoroacetone can be employed (5 vol%) in acetonitrile
providing full conversion (Table 6). This indicates that the ketone
may play a role directly in the catalysis over and above its role
as a solvent, for example through the intermediacy of ketone-
peroxide adducts such as that proposed by Que and coworkers.16
Notably sub-stoichiometric amounts of CF3COCH3 provided 90%
conversion. In this case 19F NMR spectroscopy indicated the
formation of species other than the ketone. For the hexahalo-
acetones however no conversion was observed (Table 6).
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Overall, however, the use of acetone or 2-butanone is pre-
ferred over more electron deficient ketones due to convenience,
cost and environmental reasons. The presence of significant
amounts of water in the reactions employing acetone as solvent
reduces potential hazards associated with the combination of
acetone and H2O2 significantly. In addition the activity of this
system with 2-butanone allows for oxidation of less hydrophilic
substrates.
O–O bond. The relatively slow reaction rate even in the presence
of excess H2O2 could suggest that Lewis acid activation of the
coordinated oxygen atom of the acetone H2O2 adduct by the
Mn(II) centre is important however. In such a case the oxygen
atom of the peroxide that is coordinated to the Mn(II) ion would
be rendered electrophilic in terms of its interaction with the alkene.
For electron poor alkenes addition of this oxygen atom may
be assisted by nucleophilic attack on the neighbouring carbon
atom by the –OH group of the acetone peroxide adduct. Such a
mechanism could rationalise the difference in selectivity observed
for electron rich and electron deficient alkenes.
Mechanistic considerations
With regard to the differences in maximum conversion observed
(Table 1) overall the data suggests that it is secondary oxidation
products which are responsible for catalyst inhibition. It should be
noted that the addition of acids after the reaction has commenced
slows but does not halt conversion. Hence, in the case of electron
rich alkenes (Table 2), secondary oxidation products although
formed will not inhibit that catalyst significantly (vide supra). For
the a,b-unsaturated substrates (Table 1), however, the secondary
oxidation products are likely to include oxalate monoester type
species, which may sequester the manganese efficiently and thereby
reduce or halt conversion. The qualitative correlation between the
rate of conversion of the substrate and the maximum conversion
supports this conclusion. For substrates such as maleimide and
diethyl fumarate the further oxidation of the cis-diol product
is not competitive and hence good conversion and selectivity is
observed. For less reactive substrates the further oxidation of
the cis-diol product becomes significant and hence secondary
oxidation products form, which can inhibit the reaction, before
full conversion.
The effect of variation in the parameters, i.e. solvent, co-catalyst
and base on the conversion observed provides some insight into
the reaction mechanism (Scheme 3). The first observation is the
importance of the order of addition of the reaction components.
Addition of the base, e.g., NaOAc, prior to addition of the
manganese salt and pyridine-2-carboxylic acid results in formation
of a precipitate and reduced or no reactivity. Furthermore,
replacement of the pyridine-2-carboxylic acid with pyridine-
2-carboxaldehyde shows full activity while the corresponding
N-oxide shows no activity.
Conclusions
Overall, the substrate scope for cis-dihydroxylation obtained
with MnII/pyridine-2-carboxylic acid is complimentary to the
[MnIV2O3(tmtacn)2]2+ based systems we reported recently9b,c (vide
supra) and extends the scope of alkenes that can be converted
with high turnover numbers to cis-diols using 1st row transition
metals and H2O2.18 Importantly, the system presented here is most
effective for substrates that, to date, have proven most challenging,
even for osmium based reagents. The in situ preparation of the
catalyst from readily available reagents together with its ease of
application (equally well from mg to multi-gram scale reactions,
see ESI†) and using H2O2 makes this an excellent alternative to
the RuCl3/NaIO4 based cis-dihydroxylation method for substrates
such as maleimides.6
In conclusion, we have demonstrated that the catalyst sys-
tem MnII/pyridine-2-carboxylic acid/NaOAc in acetone or 2-
butanone can achieve high turnover cis-dihydroxylation of, in par-
ticular, electron deficient trans-alkenes. From a broader perspec-
tive these results demonstrate, as shown by Burgess and co-workers
for epoxidation previously,19 that relatively simple ligand/metal
systems hold remarkable potential in achieving synthetically useful
selective oxidative transformations. Importantly, in the present
study we have shown that even at room temperature high turnover
numbers and reaction rates can be achieved. Future studies will
be directed to identifying the catalytically active species involved
in the reaction and in applying the system to other oxidative
transformations.
Scheme 3
The system is relatively insensitive to the nature of the base
employed (Table 4). The presence of a ketone in the reaction is
essential as demonstrated in the reactivity observed in acetonitrile
and MTBE (Table 6). The equilibrium between H2O2 and ketones
is well established and essentially all H2O2 in acetone or 2-
butanone solution is present as the hydrogen peroxide/ketone
adduct.16,17 This adduct is likely to be directly involved in the
catalytic cycle as no activity (and importantly no decomposition
of H2O2) is observed in acetonitrile in the absence of added ketone.
The selectivity observed, i.e. electron deficient alkenes undergo
predominantly cis-hydroxylation, electron rich alkenes undergo
epoxidation mainly, indicates that the substrate may determine
how the O–O bond is cleaved.
An important question arises as to the nature of the manganese
species that engages in activation of the peroxide to oxidise
the alkene. One possibility is the formation of a high valent
manganese-oxo species through heterolysis of the acetone peroxy
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were removed by filtration, washed several times with acetone,
after which the acetone was removed in vacuo, giving the product
as a colourless oil (1.78 g, 8.62 mmol, 92%). 1H NMR (400 MHz,
CDCl3) d 4.52 (d, J = 3.7 Hz, 2H), 4.33–4.26 (m, 4H), 3.43 (s, 2H),
1.33–1.28 (m, 6H); 13C NMR (100.6 MHz, CDCl3) d 171.6, 72.0,
62.5, 14.1; HRMS (ESI+) calc. for C8H14O6 (M+Na)+ 229.0688,
found 229.0683; elemental analysis (calc. for C8H14O6) C 45.75%
(46.60%), H 6.90% (6.84%).
Experimental section
All reagents are of commercial grade and used as received unless
stated otherwise. Hydrogen peroxide was used as received as a 50%
wt. solution in water; note that the grade of H2O2 employed can
affect the reaction where sequestrants are present as stabilizers.
The synthesis and characterization of diethyl-2-methylfumarate,20
N,N-dibutylmalediamide, 1-benzyl-1H-pyrrole-2,5-dione and
1-benzyl-3,4-dimethyl-1H-pyrrole-2,5-dione are described as
1
Competition experiment in the oxidation of diethyl fumarate and
dimethyl maleate
ESI. NMR spectra were recorded at H- (500 or 400.0 or 201.0
MHz) and 13C-NMR (100.6 or 50.0 MHz). Chemical shifts are
denoted relative to the residual solvent absorption (1H: CDCl3
7.26 ppm, DMSO-d6 2.50 ppm, CD3OD 3.31 ppm, acetone-d6
2.05 ppm; 13C: CDCl3 77.0 ppm, DMSO-d6 39.5 ppm, CD3OD
49.0 ppm). Raman spectra were recorded using a fibre optic
equipped dispersive Raman spectrometer (785 nm, Perkin Elmer
RamanFlex). Temperature was controlled using a cuvette holder
equipped with a custom made fibre optic probe holder (Quantum
Northwest). 1,2-Dichlorobenzene was employed as internal
standard for Raman spectroscopy.
1.0 mL of a stock solution in acetone (20 mL) of Mn(ClO4)2·6H2O
(7.3 mg, 20 mmol) and pyridine-2-carboxylic acid (7.5 mg, 60 mmol)
was added to a solution of 1,2 dichlorobenzene (56 mL, 0.5 mmol),
diethyl fumarate (88 mg, 0.5 mmol) and diethyl maleate (88 mg,
0.5 mmol) in acetone (1 mL). After addition of 17.0 mL of 0.6 M
(aqueous) NaOAc (2.5 mmol, 1.0 mol%), the mixture was cooled
to 5 ◦C and H2O2 (50 wt% in water, 85 mL, 0.15 mmol, 1.5 equiv.)
was added in one portion. Excess solid NaHSO3 was added to the
reaction mixture to remove residual peroxides if present (verified
1
using peroxide test-strips). The H NMR spectrum of the crude
reaction mixture was received after dilution in CDCl3 with 1,2-
dichlorobenzene as internal reference. From the integrals it is
estimated that conversion of diethyl fumarate is 90% while for
diethyl maleate the conversion is 20%. With regard to the product
distribution, integration of the absorption at ca. 4.5 ppm shows
a product distribution of 5 : 1 for the cis-diol products of diethyl
fumarate and diethyl maleate respectively.
Caution
The drying or concentration of acetone solutions that potentially
contain hydrogen peroxide should be avoided. Prior to drying or
concentrating, the presence of H2O2 should be tested for using
peroxide test strips followed by neutralisation on solid NaHSO3
or another suitable reducing agent. When working with H2O2,
especially in acetone, suitable protective safeguards should be in
place at all times.17
Acknowledgements
The authors acknowledge the Netherlands Organization for
Scientific Research (NWO) VIDI (WRB, PS) for financial support.
Caution
Perchlorate salts are potentially explosive in combination with
organic solids and solvents. In the present study manganese(II)
acetate or manganese(II) sulfate was found to give essentially iden-
tical reactivity and should be used above 2 gram reaction scales.
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9
in the oxidant H2O2
.
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4450 | Org. Biomol. Chem., 2010, 8, 4444–4450
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The Royal Society of Chemistry 2010
©