Chemoenzymatic epoxidation of alkenes by dimethyl carbonate and hydrogen peroxide

Article abstract of DOI:10.1021/ol990803v

(matrix presented) Monoperoxy carbonic acid methyl ester can be generated under neutral conditions by lipase-catalyzed perhydrolysis of dimethyl carbonate with hydrogen peroxide. It can be used in situ for the selective and efficient epoxidation of olefins; the unstable coproduct carbonic acid monomethylester decomposes to carbon dioxide and methanol. Thus, an "acid-free" Prileshajev epoxidation is realized, which is especially useful for the epoxidation of acid-sensitive substrates such as β-pinene.

Full text of DOI:10.1021/ol990803v

ORGANIC
LETTERS
1999
Vol. 1, No. 7
1025-1026
Chemoenzymatic Epoxidation of Alkenes
by Dimethyl Carbonate and Hydrogen
Peroxide
Mark Ru1sch gen. Klaas* and Siegfried Warwel
Institute for Biochemistry and Technology of Lipids, H.P. Kaufmann-Institute, Federal
Centre for Cereal, Potato and Lipid Research, D - 48147 Mu¨nster, Germany
ibtfett@uni-muenster.de
Received July 13, 1999
ABSTRACT
Monoperoxy carbonic acid methyl ester can be generated under neutral conditions by lipase-catalyzed perhydrolysis of dimethyl carbonate
with hydrogen peroxide. It can be used in situ for the selective and efficient epoxidation of olefins; the unstable coproduct carbonic acid
monomethylester decomposes to carbon dioxide and methanol. Thus, an “acid-free” Prileshajev epoxidation is realized, which is especially
useful for the epoxidation of acid-sensitive substrates such as â-pinene.
Countless processes for the epoxidation of CdC bonds have
been proposed. However, no method, including those that
are transition metal catalyzed1 or using new oxidants,2 has
been able to replace m-chloroperbenzoic acid as the work
horse in organic synthesis, although mcpba is neither cheap
nor completely harmless.
described (e.g. 5-hydroperoxycarbonylphthalimide,4 per-
fluorooxaziridines,5 methyltrioxorhenium/pyridine,6 or di-
oxiranes7), but they all suffer from various drawbacks.
Attempts have been made to use derivatives of peroxy
carbonic acid as oxidants. These derivatives have been
prepared from either carbonyl imidazoles8,9 or carbodiim-
ides,10 which both readily react with H2O2, or from peroxy-
dicarbonates11 or chloroformic esters12 under alkaline con-
ditions, so that again these methods are unsuitable for most
in situ oxidations.
Since Bjo¨rkling et al.13 converted middle chain fatty acids
with hydrogen peroxide to peroxy acids by lipase catalysis,
we used this method for the self-epoxidation of unsaturated
In the chemical industry, short chain peroxy acids are the
oxidants of choice for all epoxidations except ethylene,
propylene, and very recently butadiene. Because these short
chain peracidsspreferably performic and peracetic acids
are less stable than mcpba and therefore dangerous to be
handled or stored in large amounts, they are usually made
in situ with the help of a strong acidic catalyst (sulfuric acid,
ion exchanger). Disadvantageously, the oxidant therefore
must be buffered for most applications.3 But even in this
case the coproduct of the epoxidation is always an acid
causing numerous consecutive reactions by epoxide ring
opening. Some nonacidic oxidants for epoxidation have been
(4) James, A. P.; Johnstone, R. A. W.; McCarron, M.; Sankey, J. P.;
Trenbirth, B. J. Chem. Soc., Chem. Commun. 1988, 429.
(5) Petrov, V. A.; Resnati, G. Chem. ReV. 1996, 96, 1809.
(6) Villa de P., A. L.; De Vos, D. E.; Montes de C., C.; Jacobs, P. A.
Tetrahedron Lett. 1998, 39, 8521.
(7) Murray, R. W. Chem. ReV. 1989, 89, 1187.
(8) Staab, H. A. Angew. Chem. 1962, 74, 407.
(1) (a) Review: Jorgensen, K. A. Chem. ReV. 1989, 89, 431. (b) Recent
example: Rudolph, J.; Reddy, K. L.; Chiang, J. P.; Sharpless, K. B. J. Am.
Chem. Soc. 1997, 119, 6189.
(2) For example, see: (a) Adam, W.; Bialas, J.; Hadjiaragoplou, L. Chem.
Ber. 1991, 124, 2377. (b) Heaney, H. Top. Curr. Chem. 1993, 164, 3.
(3) Rangarajan, B.; Harvey, A.; Gruhlke, E. A.; Culnan, P. D. J. Am.
Oil Chem. Soc. 1995, 72, 1161.
(9) Tsunokawa, Y.; Iwasaki, S.; Okuda; S. Tetrahedron Lett. 1982, 2113.
(10) Murray, R. W.; Iyanar, K. J. Org. Chem. 1998, 63, 1730
(11) Coates, R. M.; Williams, J. W. J. Org. Chem. 1974, 39, 3054.
(12) Bach, R. D.; Klein, M. W.; Ryntz, R. A. Holubka, J. W. J. Org.
Chem. 1979, 44, 2569.
(13) Bjo¨rkling, F.; Godtfredsen, S. E.; Kirk, O. J. Chem. Soc., Chem.
Commun. 1990, 1302.
10.1021/ol990803v CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/25/1999

fatty acids14 and developed lipase-catalyzed perhydrolysis
of carboxylic acid esters with H2O2 acids for a variety of in
situ epoxidations.15 We found that in this way the scope of
the reaction can be extended;16 particularly, by perhydrolysis
of ethyl acetate we generated peroxy acetic acid in situ.17
We now report that dialkyl carbonates can be perhydro-
lyzed in the same way and that alkenes present are epoxi-
dized.18 Novozym 435, an immobilized lipase from Candida
antarctica, was used as the catalyst, because it has been
found to be the best lipase in terms of activity/cost;
furthermore, it is stable enough for multiple reuse.11 Any
short chain dialkyl carbonate may be perhydrolyzed, but
dimethyl carbonate was applied for the actual epoxidations,
because only dimethyl carbonate is produced industrially
from the alcohol and CO without using phosgene.19 Although
we are still looking for conclusive evidence of the peroxy
intermediate, we assume that monoperoxy carbonic acid
monomethyl ester is the active oxidant. Fortunately, no acidic
products can be found in the reaction mixture. The resulting
carbonic acid monomethyl ester probably decomposes to
methanol and CO2 under the reaction conditions. Blank
experiments without lipase gave no measurable amount of
peroxy acid under neutral conditions. The proposed reaction
mechanism is shown in Scheme 1.
was added in small portions over 6 h. Afterward the mixture
was stirred for another 16 h and dried over Na2SO4 and Na2-
SO3 to reduce the excess H2O2. Yields were determined by
GC using an internal standard. Products were identified by
comparison with authentic samples and/or by GC/MS. Larger
samples for preparative workup were distilled directly after
drying.
The results of the chemoenzymatic epoxidation of various
alkenes with dimethyl carbonate and hydrogen peroxide are
summarized in Table 1. Results of the epoxidation of the
Table 1. Epoxidation of Alkenes by Novozym 435-Catalyzed
Perhydrolysis of Dimethyl Carbonate and Ethyl Acetate
yield of epoxide (mol %)
peroxy acid generated from (solvent):
no.
alkene
1-octene
dimethyl carbonatea
ethyl acetateb
1/1
1/2
1/3
1/4
1/5
1/6
1/7
1/8
1/9
67
92
69
100
78
83
85
77
83
61-81
94
71
90
73-92
92
72
3
64
4-octene
1-tetradecene
7-tetradecene
styrene
norbornene
R-pinene
â-pinene
cyclohexene
Scheme 1. Epoxidation of Alkenes by Lipase-Catalyzed
a 0.1 mol/l alkene in dimethyl carbonate; CdC: H2O2 (60%) ) 1:5; 5
mmol CdC/g Novozym 435; 16 h; 20 °C for internal CdC; 40° for terminal
CdC. b See ref 14.
Perhydrolysis of Dimethyl Carbonate
same alkenes by Novozym 435-catalyzed perhydrolysis of
ethyl acetate are included for comparison. Upon epoxidation
of these alkenes by Novozym 435/dimethyl carbonate/H2O2,
yields of 67-100% were achieved with selectivities of >
98% (no byproducts were visible in GC spectra).
In most cases, the results of the lipase-mediated epoxida-
tion by peroxy acetic acid and monoperoxy carbonic acid
monomethyl ester are very similar. There are, however, two
notable exceptions. â-Pinene (Table 1/8), well known for
its acid-catalyzed rearrangements, cannot be epoxidized by
perhydrolysis of ethyl acetate, but using dimethyl carbonate
we achieved a good yield of 77% without any further
optimization. The epoxidation of cyclohexene with Novozym
435/ethyl acetate/H2O2 leads to about 30% diol as the
byproduct, whereas with dimethyl carbonate selectivity is
again high.
In a typical epoxidation 1 mmol of the olefin was dissolved
in 10 mL of dimethyl carbonate and 200 mg of Novozym
435 (supplied by Novo Nordisk Biotechnologie GmbH,
Mainz, Germany) was added. Then5 mmol of H2O2 (60%)
In conclusion, the epoxidation by lipase-catalyzed perhy-
drolysis of dimethyl carbonate is an easy-to-use method
especially suitable for acid-sensitive substrates. It exemplifies
the usefulness of lipase-catalyzed perhydrolysis to obtain a
variety of peracids as tailor-made oxidants.
(14) Warwel, S.; Ru¨sch gen. Klaas, M. J. Mol. Catal. B 1995, 1, 29.
(15) (a) Ru¨sch gen. Klaas, M.; Warwel, S. Lipid Technol. 1996, 77. (b)
Ru¨sch gen. Klaas, M.; Warwel, S. J. Am. Oil Chem. Soc. 1996, 73, 1453.
(c) Ru¨sch gen. Klaas, M.; Warwel, S. Synth. Commun. 1998, 28, 251. (d)
Ru¨sch gen. Klaas, M.; Warwel, S. Ind. Crops Prod. 1999, 9, 125.
(16) Ru¨sch gen. Klaas, M.; Warwel, S. J. Mol. Catal. A 1997, 117, 311.
(17) Ru¨sch gen. Klaas, M.; Warwel, S. In Proceedings of the DGMK-
Conference “SelectiVe Oxidations in Petrochemistry”; Emig, G., Kohl-
paintner, C., Lu¨cke, B., Eds.; DGMK-Tagungsbericht 9803; 1998, p 233.
(18) Warwel, S.; Ru¨sch gen. Klaas, M. Ger. Offen. DOS 19738442, 1999.
(19) Mauri, M. M.; Romano, U.; Rivetti, F. Inorg. Chim. Ital. 1985, 21,
1.
Acknowledgment. We thank the Deutsche Forschungs-
gemeinschaft (DFG) for financial support (Schwerpunktpro-
gramm “Peroxidchemie/Sauerstofftransfer”).
OL990803V
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Org. Lett., Vol. 1, No. 7, 1999