Iron Catalysed Oxidation Reactions.
Moftah Darwish and Martin Wills*
* Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
Introduction: Iron-catalyzed asymmetric epoxidation of
aromatic alkenes using iron complexes of TsDPEN derivatives,
first disclosed by Beller,1 has been studied. Epoxidation of
aromatic alkenes with hydrogen peroxide is possible using
catalyst consisting of ferric chloride hexahydrate (FeCl3.6H2O),
pyridine-2,6-dicarboxylic acid (H2pydic), and an organic base
(Figure 1).
Table 1: Epoxidation of trans-stilbene under
different conditions
Entry
H2pydic %
Solvent
Conversion
Ee
(%)
(%)
1
5
2-Methyl-2-butanol
100
41 (S,S)
2
5
2-Methyl-2-butanol
62
N/A
3
0
2-Methyl-2-butanol
0
N/A
4
5
2-Methyl-2-butanol
100
50 (S,S)
5
5
Dichloromethane
0
N/A
6
6
2-Propanol
78
34 (S,S)
7
5
Ethanol
20
5
1-Butanol
27
N/A
9
5
2-Butanol
67
N/A
10
5
tert-Butanol
92
44 (S,S)
11
6
Acetonitrile
91
39 (S,S)
* H2O2 added in one portion
Table 2: Comparison of the efficiency of additives
used in the (Figure 1)
Remarks
6 % ligand
Entry
Additive
Conversion
Ee
(%)
(%)
12
N/A
6
N/A
1
Pyridine (5 %)
2
Benzoic acid (5 %)
3
Pyridine-3-carboxaldehyde (5 %)
13
N/A
4
2-Piconilic acid (5 %)
44
N/A
5
Nicotinic acid (5 %)
7
N/A
6
Isonicotinic acid (5 %)
6
N/A
7
L-proline (5 %)
0
N/A
8
2-Piconilic acid (8 %)
71
N/A
9
2-Piconilic acid (12 %)
88
2 (S,S)
10
2,6-Pyridine dicarbonyl dichloride (5 %)
15
N/A
11
Dimethyl-2,6-pyridinedicarboxylate (5 %)
10
N/A
*
N/A
8
Results: Epoxidation of trans-stilbene under different
conditions and a comparison of the efficiency of additives
used in the epoxidation are summarized in Table 1 and Table
2. The combination of RR and SS configuration ligands
indicated no second order effect (Graph 1). Several additives
and different conditions were examined in order to establish
which groups were essential for promotion of the reaction.
Different bidentate and tetradentate ligands, were next
investigated (Figure 2). The results of these studies, and the
synthesis and applications of new ligands, is described and
comparisons drawn with related asymmetric epoxidation
processes.2-4
14% ligand
Graph 1: Non linear experiment
Entry
1
2
Ligands %
100% RR
90 % RR,10%SS
Calculated ee of ligands %
100
80
Measured ee of products%
41
35
3
4
5
6
80% RR,20%SS
70% RR,30%SS
60 % RR,40%SS
50 % RR,50%SS
60
40
20
0.0
26
17
9
0.1
Measured ee of products %
Graph 1: Non linear experiment
45
40
35
30
25
20
15
10
5
0
0
20
40
60
80
100
120
Calculated ee of ligands %
6/10/2010
Conclusion: Bidentate ligands were tested in an asymmetric epoxidation, which requires 2:1 Ligand : FeCl3.6H2O and one
equivalent of pyridine-2,6-dicarboxylic acid .The pyridine and carboxylic group are reqired for high ee. Given the possible
involvement of two equivalents of ligand in the reaction, a test for second order effects were completed by using a series of
ligands with varying ee. In addition, a series of tetradentate ligands were synthesized and evaluated in the reaction.
References:
1. Gelalcha, F. G.; Bitterlich, B.; Anilkumar, G.; Tse M. K.; Beller, M. Angew. Chem. Int. Ed. 2007, 46, 7293-7296.
2. a) Jorgensen, K. A. in Transition Metals for Organic Synthesis, vol. 2 (Ed. Beller, M.; Bolm, C.), Wiley-VCH, 1998, p. 157; b)
Sundermeier, U.; Dobler, C. in Modern Oxidation Methods (Ed. Backvall, J. E.), Wiley-VCH, Weinheim, 2004, p. 1.
3. a) Tokunaga, M.; Larraw, J.; Kakiuchi, F.; Jacobsen, E. N. Science, 1997, 277, 936-938; b) Gayet, A.; Bertilsson, S.;
Andersson, P. G. Org. Lett. 2002, 4, 3777-3779.
4. a) Katsuki, K. in Comprehensive Asymmetric Catalysis, Vol. 2 (Eds.: Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.), Springer,
Berlin, 1999, pp. 621-648; b) Johnson, R. A.; Sharpless, K. B. in catalytic asymmetric synthesis (Ed.: Ojima, I.), Wiley-VCH, New
York, 1993, pp. 103-158.
Acknowledgement: I would like to thank my supervisor Prof. Martin wills and the Libyan Government for funding of this
research project.