Enzymatic-like mediated olefins epoxidation by molecular oxygen under mild conditions

Article abstract of DOI:10.1016/j.tetlet.2007.02.066

Highly efficient epoxidation of olefins by molecular oxygen with catalytic amount of manganese meso-tetraphenylporphyrin (Mn(TPP)) at the ppm level were reported. The catalyst conferred high activity and selectivity for the olefins epoxidation under ambient temperature and atmospheric pressure. The turnover number (TON) of the catalyst could reach up to 700 million, which is comparable to enzyme catalysis.

Full text of DOI:10.1016/j.tetlet.2007.02.066

Tetrahedron Letters 48 (2007) 2691–2695
Enzymatic-like mediated olefins epoxidation by molecular
oxygen under mild conditions
Xian-Tai Zhou,a Hong-Bing Ji,a,* Jian-Chang Xu,a Li-Xia Pei,a
Le-Fu Wanga and Xing-Dong Yaob
aSchool of Chemical and Energy Engineering, South China University of Technology, Guangzhou 510640, China
bCollege of Chemistry and Ecological Engineering, Guangxi University for Nationalities, Nanning 530006, China
Received 9 January 2007; revised 13 February 2007; accepted 14 February 2007
Available online 16 February 2007
Abstract—Highly efficient epoxidation of olefins by molecular oxygen with catalytic amount of manganese meso-tetraphenylpor-
phyrin (Mn(TPP)) at the ppm level were reported. The catalyst conferred high activity and selectivity for the olefins epoxidation
under ambient temperature and atmospheric pressure. The turnover number (TON) of the catalyst could reach up to 700 million,
which is comparable to enzyme catalysis.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
for the epoxide products. Mandal and Iqbal used
0.125 mmol cobalt(II) porphyrin catalyst in the epoxida-
tion of cyclohexene (5 mmol) with 2-methyl propanal
and molecular oxygen, and obtained the cyclohexene
epoxide in 16% yields.10
Metalloporphyrins as model catalysts of cytochrome
P-450 have been used to mimic various oxidation
reactions, for example, hydroxylation of hydrocarbon,
epoxidation of olefins under mild conditions.1 During
the past two decades, metalloporphyrins have been
widely applied for epoxidation of olefins to give epox-
ides with high regio-, shape- and stereoselectivity since
the leading works of Groves and co-workers.2 A variety
of oxidants, such as PhIO,3 H2O2,4 MMPP (magnesium
monoperoxyphthalate),5 TBAO (tetrabutylammonium
monosulfate),6 and n-Bu4NIO4 (tetrabutylammonium
periodate),7 in combination with different metallopor-
phyrin catalysts have been employed as oxygen atom
donors.
In our earlier studies on cyclohexane and nitrotoluene
oxidation with dioxygen catalyzed by metalloporphyrins
and metallophthalocyanines,11 high product yields and
TONs of catalysts with low dosages have been observed.
As a part of our ongoing interest in metalloporphyrins-
catalyzed oxidations, the epoxidation of alkenes cata-
lyzed by very small amount of Mn(TPP) has presently
been developed. This catalyst proved to be an effective
catalyst in epoxidation systems with extremely high
turnover number in the presence of molecular oxygen
and isobutylaldehyde (Scheme 1), which is comparable
to most enzyme catalysis.
The selective aerobic oxidation of hydrocarbons cata-
lyzed by metalloporphyrins is attracting more interests
because of its low cost and the environmentally friendly
nature of the oxidant.8 In metalloporphyrin catalyzed
homogenous epoxidation of olefins, aldehyde is usually
used as a reducing agent in the presence of molecular
oxygen for the reductive activation of oxygen. Haber
reported a successful aerobic epoxidation of propylene
with Mn(TPP)Cl in the presence of propionaldehyde.9
The TON of the catalyst was about 7 cycles per minute
Ph
N
Mn
N
N
N
Ph
Ph
R1
R2
R3
R4
R1 O R3
R2 R4
Ph
CH2Cl2, isobutyraldehyde, O2 (1 atm), r.t.
*
Scheme 1. Manganese meso-tetraphenylporphyrin catalyzed epoxida-
Corresponding author. Tel./fax: +86 20 87114136; e-mail: cehbji@
tion of olefins.
scut.edu.cn
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.02.066

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X.-T. Zhou et al. / Tetrahedron Letters 48 (2007) 2691–2695
2. Reaction conditions of cyclohexene epoxidation
tive solvent for the epoxidation despite a little decrease
of the catalytic activity (entry 10).
Various amounts of Mn(TPP) catalyst,12,13 that is,
10,000, 100, 10, 1 and 0.1 ppm (based on substrate), were
used in the epoxidation of cyclohexene with molecular
oxygen as oxidant in the presence of isobutyraldehyde.14
All the reactions proceeded with high conversion and
high selectivity for the desired cyclohexene epoxide by
using a substrate-to-isobutraldehyde molar ratio of 1:5
(Table 1).
3. Epoxidation of various substrates catalyzed by man-
ganese meso-tetraphenylporphyrin
Encouraged by the excellent catalytic performance for
the cyclohexene epoxidation, various alkenes were sub-
jected to the reaction system at room temperature in
the presence of atmospheric oxygen using only 1 ppm
of catalyst (Table 2).
From Table 1, the simple structural manganese meso-
tetraphenylporphyrin catalyst presented excellent cata-
lytic performance for cyclohexene epoxidation under
mild condition. As the amount of catalyst varied from
10,000 ppm to 0.1 ppm, more than 95% yields of cyclo-
hexene oxide could be obtained within 2–5 h in the pres-
ence of molecular oxygen and isobutyraldehyde (entries
1–5). On the contrary, only 15% cyclohexene could be
converted without the catalyst, indicating that the man-
ganese meso-tetraphenylporphyrin catalyst is crucial for
the epoxidation (entry 6). The importance of isobutyral-
dehyde in the epoxidation was also investigated. In the
absence of isobutyraldehyde, neither cyclohexene epox-
ide nor 2-cyclohexen-1-ol and 2-cyclohexen-1-one could
be obtained by conducting the reaction for 4.5 h (entry
7), strongly implying that the manganese meso-tetra-
phenylporphyrin catalyst could not realize the catalytic
cycle without aldehyde as an oxygen acceptor. Thus
the epoxidation with various molar ratios of substrate
to isobutyraldehyde were examined. When the sub-
strate/isobutyraldehyde molar ratio was increased to
1:4, 78% cyclohexene could be converted (entry 8), while
higher molar ratio of the substrate to isobutyraldehyde
gave higher conversion (entry 9). However, no signifi-
cant difference was observed when the substrate/iso-
butyraldehyde molar ratio reached 1:5 for the present
system. It should be noted that the catalytic efficiency
of the metalloporphyrin was extremely high and the
TON of 78,836,263 could be easily obtained (entry 5).
Other solvent, such as toluene, could also be an alterna-
As shown in Table 2, all substrates could be smoothly
converted to epoxies with high conversion rates and
excellent selectivities. It seems that the efficiency of
epoxidation in this catalytic system is very dependent
on the steric structure of substrates. For example, the
conversion of cyclohexene was 97% (entry 1), other
functional groups on the C@C bond, for example,
1-methylcyclohexene and 1-phenylcyclohexene, lowered
the catalytic activities giving 93% and 83% conversion,
respectively (entries 2–3). The influence of steric effects
could further be found when styrene and its derivatives
were oxidized, the conversion rates of styrene, trans-b-
methylstyrene and trans-stilbene were 95%, 89% and
86% after reacting for 4.5, 7.0 and 8.0 h, again demon-
strating a steric effect (entries 4–6).
Similarly, in the epoxidation of other cycloolefin, for
example, cyclooctene, the reaction system exhibits high
catalytic performance with 93% yield of cyclooctene
epoxide (entry 7). Epoxidation of linear chains, for
example, 1-octene and trans-2-octene smoothly
proceeded with high conversion and yield, and similar
catalytic activities for the two substrates show the
located position of C@C bond on linear chain alkenes
could hardly influence their catalytic performance
(entries 8–9).
Despite the high efficiency of the catalyst system,
another salient feature of the present epoxidation is its
high regioselectivity. When (+)-limonene was subjected
to the epoxidation, the monoepoxide with the epoxide
group on the ring was the only product and its yield
was 91% (entry 10). In addition, the catalyst system
exhibits specific selective oxidation performance
towards C@C bond and hydroxyl group activation.
C@C bond was preferentially activated and the corre-
sponding epoxide as the only product with 90% yield
could be obtained for the cinnamyl alcohol oxidation,
and no products from hydroxyl group oxidation could
be detected (entry 11).
Table 1. Epoxidation of cyclohexene catalyzed by manganese meso-
tetraphenylporphyrin in the presence of molecular oxygena
Entry Amount of
Reaction Conv. Yield TON
catalyst (ppm) Time (h) (%)
(%)
1
2
3
4
5
6b
7c
8d
9e
10f
10,000
100
10
1.0
0.1
0
1.0
1.0
1.0
1.0
2.0
2.5
4.0
4.5
5.0
5.0
4.5
4.5
4.5
4.5
>99
>99
98
97
97
15
0
78
>99
85
97
98
95
95
96
13
0
76
98
82
813
81,274
796,490
7,883,626
78,836,263
—
0
6,339,410
8,127,450
6,908,332
The extremely high catalytic performance (comparable
to enzymes) exhibited by manganese meso-tetra-
phenylporphyrin is most interesting. In order to gain
insight into the likely reasons, the epoxidation pro-
cesses of cyclohexene in the presence of isobutyralde-
hyde and molecular oxygen with different amounts of
catalyst of 10,000, 100, 10, 1, 0.1 ppm (based on sub-
strate) were tracked. The reaction profiles are shown
in Figure 1.
a Substrate (2 mmol), isobutylaldehyde (0.01 mol), CH2Cl2 (5 mL), O2
bubbling, rt.
b No catalyst.
c No aldehyde.
d Molar ratio of cyclohexene to isobutyraldehyde was 1:4.
e Molar ratio of cyclohexene to isobutyraldehyde was 1:6.
f Toluene as solvent.

X.-T. Zhou et al. / Tetrahedron Letters 48 (2007) 2691–2695
2693
Table 2. Epoxidation of alkenes catalyzed by manganese meso-tetraphenylporphyrin in the presence of molecular oxygen and isobutyraldehydea
Entry
1
Substrate
Product
Reaction time (h)
4.5
Conv. (%)
97
Yield (%)
95
O
2
3
4
5
6
5.0
6.0
4.5
7.0
8.0
93
83
95
89
86
90
72
93
87
85
O
Ph
Ph
O
O
O
O
7
5.0
95
93
O
8
9
5.0
5.0
94
93
93
89
O
O
O
10
11
5.0
6.0
92
92
91
90
O
OH
OH
a Substrate (2 mmol), isobutyraldehyde (0.01 mol), CH2Cl2 (5 mL), O2 bubbling, rt.
Although the amount of the catalyst decreased exponen-
tially, cyclohexene could be nearly stoichiometrically
oxidized within the reaction times ranged from 2.0 to
5.0 h, as shown in Figure 1. When the amount of cata-
lyst was 1 or 0.1 ppm, the reaction displays an induction
period, then followed by a sharp acceleration until
completion. When a radical scavenger such as tetra-
chloromethane was added to the reaction system, the
conversion was stopped and no product could be
detected after 5 h, even with 10,000 ppm catalyst. There-
fore, the epoxidation catalyzed by metalloporphyrin
should involve radical species. The result is consistent
with those of Qi,15 Nam,16 and Ravikumar17 using
ruthenium complex, cyclam or manganese acetate dihy-
drate as catalysts. Further studies on the mechanism of
the epoxidation are in progress.
100
80
60
40
20
0
10000 ppm
100 ppm
10 ppm
1 ppm
0.1 ppm
0
1
2
3
4
5
4. Large scale epoxidation of cyclohexene
Time/h
A large scale of cyclohexene epoxidation experiment was
carried out in the presence of molecular oxygen and iso-
butyraldehyde as shown in Scheme 2.18
Figure 1. Profile of the conversion rates of cyclohexene oxide for
different amounts of Mn(TPP): substrate (2 mmol), isobutyraldehyde
(0.01 mol), CH2Cl2 (5 mL), O2 bubbling (1 atm), rt.

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X.-T. Zhou et al. / Tetrahedron Letters 48 (2007) 2691–2695
Mn(TPP) (0.1 ppm)
O
CH2Cl2 (50 mL), isobutyraldehyde (0.1 mol), O2 (1 atm), 10 h, r.t.
20 mmol
isolated yield: 90%
TON: 731,470,480
Scheme 2. Large scale epoxidation of cyclohexene.
When the amount of manganese meso-tetraphenyl-
porphyrin catalyst was 2.5 · 10À8 mmol, the cyclo-
hexene oxide could be obtained with the isolated yield
of 90%. It should be mentioned that the turnover
number of the present catalyst could reach
731,470,480. Since commonly, TOF is used to express
the catalytic efficiency of enzyme with the definition as
converted substrate (mol) per enzyme (mol) per minute.
The TOF of most enzymes is about 1000 minÀ1 or more.
For example, the TOF of catalase is 6 · 106 minÀ1, and
the TOF of b-galactosidase is 1.25 · 104 minÀ1. In the
present manganese meso-tetraphenylporphyrin cata-
New Century Excellent Talents in University (NCET)
for the financial support.
References and notes
1. Meunier, B. Biomimetic Oxidations Mediated by Metal
Complexes; Imperial College Press: London, 2000.
2. (a) Groves, J. T.; Nemo, T. E. J. Am. Chem. Soc. 1983,
105, 5786–5791; (b) Dolphin, D.; Traylor, T. G.; Xie, L.
Y. Acc. Chem. Res. 1997, 30, 251–259; (c) do Nascimento,
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Reboucas, J. S.; Idemori, Y. M. J. Inorg. Biochem. 2005,
99, 1193–1204.
lyzed system, the TOF reaches up to 1.2 · 106 minÀ1
,
which is the range for enzyme activity.
3. (a) Gross, Z.; Ini, S. J. Org. Chem. 1997, 62, 5514–5521;
(b) de Sousa, A. N.; de Carvalho, M. E. M. D.; Idemori,
Y. M. J. Mol. Catal. A 2001, 169, 1–10; (c) Li, Z.; Xia, C.
G.; Ji, M. Appl. Catal., A 2003, 252, 17–21.
5. Cyclohexene epoxidation catalyzed by Fe(III) and
Co(II) porphyrins
4. (a) Campestrini, S.; Tonellato, U. J. Mol. Catal. A 2001,
171, 37–42; (b) Gonsalves, A. M. D. R.; Serra, A. C. J.
Porphyrins Phthalocyanines 2000, 4, 598–603; (c) Nam,
W.; Oh, S.-Y.; Sun, Y. J.; Kim, J.; Kim, W.-K.; Woo, S.
K.; Shin, W. J. Org. Chem. 2003, 68, 7903–7906.
5. (a) Haber, J.; Iwanejko, R.; Poltowicz, J.; Battioni, P.;
Mansuy, D. J. Mol. Catal. A 2000, 152, 111–115; (b)
Haber, J.; Iwanejko, R.; Poltowicz, J.; Battioni, P.;
Mansuy, D. J. Mol. Catal. A 2000, 152, 117–120.
6. Mohajer, D.; Rezaeifard, A. Tetrahedron Lett. 2002, 43,
1881–1884.
Other simple structural metalloporphyrins, for example,
iron and cobalt porphyrins, have similar catalytic per-
formance for epoxidation of cyclohexene in the presence
of molecular oxygen and isobutyraldehyde. When using
1 ppm loading of iron meso-tetraphenylporphyrin chlo-
ride (Fe(TPP)Cl) or cobalt meso-tetraphenylporphyrin
Co(TPP)13 as catalyst in the epoxidation of cyclohexene
under the same reaction conditions, 95% and 89% yields
of cyclohexene oxide were obtained, respectively. These
results indicate that the metalloporphyrins are effective
catalysts for epoxidation of cyclohexene with ppm level
catalytic amount by using molecular oxygen as an
oxidant.
7. Mohajer, D.; Karimipour, G.; Bagherzadeh, M. New J.
Chem. 2004, 28, 740–747.
8. (a) Lyons, J. E.; Ellis, P. E. J. Catal. 1995, 155, 59–73; (b)
Haber, J.; Matachowski, L.; Pamin, K.; Poltowicz, J. J.
Mol. Catal. A 2000, 162, 105–109; (c) Guo, C. C.; Chu, M.
F.; Liu, Q.; Liu, Y.; Guo, D. C.; Liu, X. Q. Appl. Catal., A
2003, 246, 303–309; (d) Haber, J.; Matachowski, L.;
Pamin, K.; Poltowicz, J. J. Mol. Catal. A 2003, 198, 215–
221; (e) Ellis, S.; Kozhevnikov, I. V. J. Mol. Catal. A 2002,
187, 227–235.
9. Haber, J.; Mlodnicka, T.; Poltowicz, J. J. Mol. Catal.
1989, 54, 451–461.
10. Mandal, A. K.; Iqbal, J. Tetrahedron 1997, 53, 7641–
7648.
It has been shown that the steric and electronic proper-
ties of substituent on the porphyrin rings or axial ligands
could affect the catalytic performance of metalloporphy-
rins.19 Further studies on substituent and axial ligands
effects of catalytic activity for olefins epoxidation are
in progress.
In conclusion, simple structural manganese meso-tetra-
phenyl porphyrin has proven to be an excellent catalyst
for the epoxidation of olefins in the presence of mole-
cular oxygen and isobutylaldehyde. Under ambient
temperature and atmospheric pressure, the catalytic
system displays high activity and selectivity for olefins
epoxidation by using ppm level catalyst. The turnover
number of catalyst could reach up to 731,470,480.
11. (a) Yuan, Y.; Ji, H. B.; Chen, Y. X.; Han, Y.; Song, X. F.;
She, Y. B.; Zhong, R. G. Org. Process Res. Dev. 2004, 8,
418–420; (b) Song, X. F.; She, Y. B.; Ji, H. B.; Zhang, Y.
H. Org. Process Res. Dev. 2005, 9, 297–301.
12. meso-Tetraphenylporphyrin (TPP) was prepared accord-
ing to the known procedure, see: Alder, A. D.; Longo, F.
R.; Finarelli, J. D.; Goldmacher, J.; Assour, J.; Korsakoff,
L. J. Org. Chem. 1967, 32, 476.
13. Metalloporphyrins were prepared according to our previ-
ous works, see: Refs. 11a and 19a. The spectral and
analysis data of Mn(TPP). FAB: m/z 667. Anal. Calcd for
C44H28N4Mn: C, 79.08; H, 4.19; N, 8.39. Found: C, 79.26;
H, 4.05; N, 8.32. UV–vis (CH2Cl2) kmax: 424 nm (Soret
band), 545 nm (Q-band). IR: 1002 cmÀ1. The spectral and
analysis data of Fe(TPP)Cl. FAB: m/z 705. Anal. Calcd
Acknowledgements
The authors thank the National Natural Science Foun-
dation of China (No. 20576045) and the Program for

X.-T. Zhou et al. / Tetrahedron Letters 48 (2007) 2691–2695
2695
for C44H28N4FeCl: C, 74.98; H, 3.98; N, 7.95. Found: C,
6632–6633; (b) Nam, W.; Kim, H. J.; Kim, S. H.; Ho, R.
Y. N.; Valentine, J. S. Inorg. Chem. 1996, 35, 1045–1049.
17. Ravikumar, K. S.; Barbier, F.; Begue, J. P.; Delpon, D. B.
Tetrahedron 1998, 54, 7457–7464.
75.12; H, 4.01; N, 7.89. UV–vis (CH2Cl2) kmax: 418 nm
(Soret band), 548 nm (Q-band). IR: 1006 cmÀ1; 325 cmÀ1
.
The spectral and analysis data of Co(TPP). FAB: m/z 671.
Anal. Calcd for C44H28N4Co: C, 78.61; H, 4.17; N, 8.34.
18. General procedure for the large scale cyclohexene catalytic
epoxidation. To a stirring solution of dichloromethane
(50 mL), cyclohexene (20 mmol), isobutylaldehyde
(0.1 mol) and manganese meso-tetraphenylporphyrin
(2.5 · 10À8 mmol) were added in the presence of molecular
oxygen at room temperature. The crude products were
purified via column chromatography (silica gel, cyclohex-
ane as eluting agent). After removing solvent under
reduced pressure, the pure cyclohexene oxide (1.76 g)
was obtained with the yield of 90%.
19. (a) Wang, L. Z.; She, Y. B.; Zhong, R. G.; Ji, H. B.;
Zhang, Y. H.; Song, X. F. Org. Process Res. Dev. 2006, 10,
757–761; (b) Arasasingham, R. D.; He, G. X.; Bruice, T.
C. J. Am. Chem. Soc. 1993, 115, 7985–7991; (c) Chan, W.
K.; Wong, M. K.; Che, C. M. J. Org. Chem. 2005, 70,
4226–4232.
Found: C, 78.32; H, 4.05; N, 8.19. UV–vis (CH2Cl2) kmax
:
425 nm (Soret band), 552 nm (Q-band). IR: 1004 cmÀ1
.
14. General procedure for the catalytic epoxidation of alkenes
to epoxides. Dioxygen was bubbled through a solution of
dichloromethane (5 mL), cyclohexene (2 mmol), isobutyl-
aldehyde (10 mmol), manganese meso-tetraphenylporphy-
rin (2.5 · 10À7 mmol) and 0.8 mmol naphthalene (inert
internal standard) at room temperature. The consumption
of the starting olefins and formation of oxidized products
were monitored by GC (Shimadzu GC14C) and GC–MS
(Shimadzu GCMS-QP5050A).
15. Qi, J. Y.; Qiu, L. Q.; Lam, K. H.; Yip, C. W.; Zhou, Z. Y.;
Chan, A. S. C. Chem. Commun. 2003, 1058–1059.
16. (a) Nam, W.; Baek, S. J.; Lee, K. A.; Ahn, B. T.; Muller, J.
G.; Burrows, C. J.; Valentine, J. S. Inorg. Chem. 1996, 35,