Iron Catalysed Oxidation Reactions.Moftah Darwish and Martin Wills*

* Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.

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.

 

Entry H2pydic % Solvent Conversion

(%)

Ee

(%)

Remarks

1 5 2-Methyl-2-butanol 100 41 (S,S)

2 5 2-Methyl-2-butanol 62 N/A 6 % ligand

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 N/A

8 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) 14% ligand

Table 1: Epoxidation of trans-stilbene under different conditions

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

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).

Entry Additive Conversion

(%)

Ee

(%)

1 Pyridine (5 %) 12 N/A

2 Benzoic acid (5 %) 6 N/A

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

Table 2: Comparison of the efficiency of additives used in the (Figure 1)

* H2O2 added in one portion

Graph 1: Non linear experiment

6/10/2010

Entry Ligands % Calculated ee of ligands % Measured ee of products%1 100% RR 100 412 90 % RR,10%SS 80 35

3 80% RR,20%SS 60 264 70% RR,30%SS 40 175 60 % RR,40%SS 20 96 50 % RR,50%SS 0.0 0.1

O

+ H2O2 (3 eq.)

FeCl3.6H2O (5 mol%)H2pydic (5 mol%)

2-methylbutan-2-olLigand (10 % mol%)

Ph

(R)(R)

PhHN

NHBn

SO2

Ph (S)

(S)

Ph HN

NHBn

SO2

05

1015202530354045

0 20 40 60 80 100 120

Me

asu

red

ee

of

pro

du

cts

%

Calculated ee of ligands %

Graph 1: Non linear experiment

NHBn

NHBnHNTsHN

NHBn

NHTs

100 % Conversion 50 % ee (S,S)

100 % conversion 9 % ee (R,R)

71 % Conversion38 % ee(S,S)

94 % conversion16 % ee (R,R)

Figure 2: Results with some ligands

SO2

HN

HN

TsHN

TsHN

30 % Conversion3 % ee(R,R)

TsHN

HN O2S

MeO

HN

NH

95 % Conversion 44 % ee (R,R)

FeCl3.6H2O (5 mol%)H2pydic (5 mol%)

ligand (12 mol%)

2-Methylbutan-2-ol

O

+

O

+ H2O2 (2 eq.)

Ph

PhHN

NHBn

SO2

100 % Conversion 41% ee (S,S)

NHO2C CO2HH2pydic =