Asymmetric epoxidation of olefins with chiral bioinspired manganese complexes

Article abstract of DOI:10.1021/ol901400m

Image Presented A novel series of chiral tetradentate N₄ ligands together with their manganese complexes have been designed and synthesized. With 1 mol % manganese catalyst loading, the enantioselective epoxidation of olefins proceeds with nearly full conversion and enantiomeric excess values of up to 89 % for the first time.

Full text of DOI:10.1021/ol901400m

ORGANIC
LETTERS
2009
Vol. 11, No. 16
3622-3625
Asymmetric Epoxidation of Olefins with
Chiral Bioinspired Manganese
Complexes
Mei Wu,†,‡ Bin Wang,†,‡ Shoufeng Wang,† Chungu Xia,*,† and Wei Sun*,†
State Key Laboratory for Oxo Synthesis and SelectiVe Oxidation, Lanzhou Institute of
Chemical Physics, Chinese Academy of Sciences, Lanzhou, 730000, P. R. China, and
Graduate School of the Chinese Academy of Sciences, Beijing, 100039, P. R. China
wsun@lzb.ac.cn; cgxia@lzb.ac.cn
Received June 20, 2009
ABSTRACT
A novel series of chiral tetradentate N4 ligands together with their manganese complexes have been designed and synthesized. With 1 mol
% manganese catalyst loading, the enantioselective epoxidation of olefins proceeds with nearly full conversion and enantiomeric excess
values of up to 89 % for the first time.
The asymmetric epoxidation of olefins is a very important
organic transformation since the resulting enantiomerically
pure epoxides are highly useful intermediates and building
blocks.1 Many efforts have been dedicated to the develop-
ment of chiral catalysts that can perform an asymmetric
epoxidation reaction effectively. The most successful ex-
amples are the chiral metal-salen complexes and their
complexes, Fe and Mn complexes derived from N,N′-
dimethyl-N,N′-bis(2-pyridylmethyl) ethane-1,2-diamine (mep)
and (R,R)-N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)cyclohex-
ane-1,2-diamine (R,R-mcp), have been synthesized and
utilized in the oxidation reaction.4,5 A major breakthrough
(3) (a) Matsumoto, K.; Sawada, Y.; Saito, B.; Sakai, K.; Katsuki, T.
Angew. Chem., Int. Ed. 2005, 44, 4935. (b) Sawada, Y.; Matsumoto, K.;
Kondo, S.; Watanabe, H.; Ozawa, T.; Suzuki, K.; Saito, B.; Katsuki, T.
Angew. Chem., Int. Ed. 2006, 45, 3478. (c) Matsumoto, K.; Sawada, Y.;
Katsuki, T. Synlett 2006, 3545. (d) Sawada, Y.; Matsumoto, K.; Katsuki,
T. Angew. Chem., Int. Ed. 2007, 46, 4559. (e) Kondo, S.; Saruhashi, K.;
Seki, K.; Matsubara, K.; Miyaji, K.; Kubo, T.; Matsumoto, K.; Katsuki, T.
Angew. Chem., Int. Ed. 2008, 47, 10195.
derivatives.1 2,3 In recent years, biologically inspired tet-
,
radentate nitrogen (N4) based ligands and their metal
† Lanzhou Institute of Chemical Physics.
‡ Graduate School.
(1) (a) Wong, O. A.; Shi, Y. Chem. ReV. 2008, 108, 3958. (b) Lane,
B. S.; Burgess, K. Chem. ReV. 2003, 103, 2457. (c) Xia, Q. H.; Ge, H. Q.;
Ye, C. P.; Liu, Z. M.; Su, K. X. Chem. ReV. 2005, 105, 1603. (d) Porter,
M. J.; Skidmore, J. Chem. Commun. 2000, 1215. (e) D´ıez, D.; Nu´n˜ez, M. G.;
Anto´n, A. B.; Garc´ıa, P.; Moro, R. F.; Garrido, N. M.; Marcos, I. S.; Basabe,
P.; Urones, J. G. Curr. Org. Synth. 2008, 5, 186.
(4) (a) White, M. C.; Doyle, A. G.; Jacobsen, E. N. J. Am. Chem. Soc.
2001, 123, 7194. (b) Costas, M.; Tipton, A. K.; Chen, K.; Jo, D. H.; Que,
L., Jr. J. Am. Chem. Soc. 2001, 123, 6722. (c) Chen, M. S.; White, M. C.
Science 2007, 318, 783. (d) Suzuki, K.; Oldenburg, P. D.; Que, L., Jr. Angew.
Chem., Int. Ed. 2008, 47, 1887. (e) Oldenburg, P. D.; Que, L., Jr. Catal.
Today 2006, 117, 15.
(2) (a) Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am.
Chem. Soc. 1990, 112, 2801. (b) Irie, R.; Noda, K.; Ito, Y.; Matsumoto,
N.; Katsuki, T. Tetrahedron Lett. 1990, 31, 7345. (c) McGarrigle, E. M.;
(5) (a) Murphy, A.; Dubois, G.; Stack, T. D. P. J. Am. Chem. Soc. 2003,
125, 5250. (b) Murphy, A.; Pace, A.; Stack, T. P. D. Org. Lett. 2004, 6,
3119. (c) Murphy, A.; Stack, T. D. P. J. Mol. Catal. A: Chem. 2006, 251,
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Gilheany, D. G. Chem. ReV. 2005, 105, 1563
.
10.1021/ol901400m CCC: $40.75
Published on Web 07/24/2009
 2009 American Chemical Society

in the field has been done by Que and co-workers who
reported highly enantioselective cis-dihydroxylation of alk-
enes with synthetic Fe complexes of N4 ligands.4d Stack and
co-workers recently described manganese complexes of N4
ligands that in combination with peracetic acid (AcOOH)
act as very fast and efficient epoxidation agents. Unfortu-
nately, asymmetric version with this highly active manganese
catalyst has proven to be a challenging task.5,6 Subsequently,
Costas and co-workers have demonstrated that manganese
complexes with chiral tetradentate N4 ligands derived from
(R,R-mcp) by fusing pinene rings can promote the epoxida-
tion reaction with modest yet remarkable enantiomeric
excess.7 Pfaltz and co-workers have prepared a series of
chiral N4 ligands containing two oxazoline rings instead of
pyridine rings, and their manganese complexes only exhibit
low enantioselectivities in the epoxidation reaction.8
crystals suitable for X-ray crystallographic analysis were
afforded from MeCN/ether, formulated as [MnII(pmcp)-
(CF3SO3)2] (4) and [MnII(nmcp) (CF3SO3)2] (5). In both
structures, the ligands coordinate the manganese center in a
cis-R topology (Figure 2).12
Obviously, more endeavors need to be made to these
biomimetic systems. As a part of continuous interest in the
asymmetric oxidation,9 we describe herein the development
of a novel family of chiral Mn(II) complexes of N4 ligands
for asymmetric epoxidation of unfunctionalized olefins and
enones1d,e,10 with H2O2, in the presence of acetic acid. With
1 mol % catalyst loading, the enantioselective epoxidation
of olefins proceeds with nearly full conversion and enantio-
meric excess values of up to 89% for the first time.
Pioneering studies by Stack and co-workers have dem-
onstrated that a 10% ee for epoxidation of vinyl cyclohexane
was observed and catalyzed by [MnII(R,R-mcp)(CF3SO3)2]
(OTf ) trifluoromethane sulfonate) with AcOOH as
oxidant.6a On the basis of the previous research work,
aromatic groups were introduced into both of the 2-pyridyl-
methyl positions (C7 and C7′, as shown in Figure 1, R,R-
Figure 2.
X-ray structures of MnII complex 4 and 5 with thermal
ellipsoids drawn at the 50% probability level. Hydrogen atoms are
omitted for clarity (C, gray; N, blue; O, red; F, green; S, yellow;
Mn, pink).
-
Jacobsen et al. have found FeII(mep) with SbF6 coun-
terions to be an efficient epoxidation catalyst with H2O2 in
the presence of acetic acid (AcOH).4a Que et al. have
determined that iron complexes of N4 ligands catalyze in
situ formation of AcOOH from H2O2 and AcOH.13a Very
recently, Costas described a method for the epoxidation of
olefins using H2O2/AcOH oxidant.13b In preliminary studies,
we evaluated the catalytic property of these new catalysts
in the asymmetric epoxidation of styrene with H2O2 as
oxidant, in the presence of acetic acid (Table 1). All of the
Table 1. Screening of the Catalysts and Reaction Conditionsa
a Reactions were carried out in 1.5 mL of MeCN at room temperature
with 0.25 mmol of styrene or chalcone, 1 mol % catalyst, 6 equiv of H2O2,
and 5 equiv of AcOH. b For styrene, GC yield; for chalcone, isolated yield.
c For details, see Supporting Information. d 3 equiv of H2O2, 5 equiv of
AcOH.
Figure 1. Chiral ligands used in this study.
examined catalysts demonstrated excellent catalytic activity
under the optimal conditions. The influence of the aromatic
substituents on the enantioselectivity of the catalysis was
dramatic. The complex 6 bearing 4-t-Bu-phenyl groups on
the C7 and C7′ positions exhibited 43% ee (Table 1, entry
2). MnII complex 4 [MnII(pmcp)(CF3SO3)2] was employed
mcp) of the ligand of R,R-mcp. To this end, several novel
N4 ligands were prepared, and corresponding manganese(II)
complexes were obtained by the reactions of equimolar
amounts of ligand and MnII(OTf)2 in MeCN under an argon
atmosphere at room temperature for 2 h.11 The off-white
Org. Lett., Vol. 11, No. 16, 2009
3623

in the asymmetric epoxidation, affording the epoxide product
in an 89% yield and 46% ee (Table 1, entry 3). However,
MnII(R,R-mcp) only gave rise to 26% ee in the asymmetric
epoxidation of styrene (Table 1, entry 5) under the same
conditions. Chalcone was also selected as a model substrate;
78% ee was observed using complex 6 as catalyst (Table 1,
entry 8). This is a great improvement in enantioselectivity
compared to those displayed by the system with previously
reported chiral bioinspired manganese catalysts.6-8
epoxidized with higher enantioselectivities (Table 2, entry
6, up to 63% ee) than previously reported, although ee values
still fall short of synthetically useful levels.6a,7,8
To further demonstrate the substrate scope and the potential
for the asymmetric bioinspired epoxidation, the enantioselective
epoxidation of a variety of R,ꢀ-unsaturated ketones was also
evaluated by using complex 6 under the same conditions. As
summarized in Table 3, the reactions proceeded efficiently and
Encouraged by these preliminary results, the catalysis of
the enantioselective epoxidation of a variety of unfunction-
alized olefins was then investigated by using complex 6 with
H2O2/AcOH oxidant (Table 2). For most tested substrates,
Table 3. Asymmetric Epoxidation of R,ꢀ-Enones Catalyzed by
Complexes 6a
Table 2. Asymmetric Epoxidation of Unfunctionalized Olefins
Catalyzed by Complexes 6a
entry
R1
R2
yieldb
eec
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
p-Cl-C6H4
o-Cl-C6H4
o-Br-C6H4
p-Me-C6H4
p-F-C6H4
Ph
Ph
91 (10a)
63 (10b)
82 (10c)
89 (10d)
72 (10e)
52 (10f)
89 (10g)
87 (10h)
87 (10i)
72 (10j)
94 (10k)
90 (10l)
94 (10m)
78 (2R,3S)
76 (2R,3S)
86 (2R,3S)
72 (2R,3S)
80 (2R,3S)
70 (2R,3S)
85 (2R,3S)
86 (2R,3S)
89 (2R,3S)
85 (2R,3S)
81 (2R,3S)
82
p-MeO-C6H4
p-NO2-C6H4
p-Cl-C6H4
p-Me-C6H4
2-naphthyl
Ph
Ph
Ph
Ph
Ph
9
10
11
12
13
p-F-C6H4
p-Me-C6H4
p-F-C6H4
79
a Reactions were carried out in 1.5 mL of MeCN for 60 min at room
temperature with 0.25 mmol of substrates, 1 mol % complex 6, 6 equiv of
H2O2, and 5 equiv of AcOH. b Isolated yield. c Determined by HPLC with
a Daicel chiral column (for details see Supporting Information).
rapidly to give the corresponding epoxides in >80% yields with
moderate to excellent enantioselectivities for most cases (70-89%
ee). Clearly, the substituted groups of different electronic
characters on the phenyl ring of the carbonyl side influenced
the reaction activities and enantioselectivities (Table 3, entries
1-6). Substitution by the p-NO2 group led to a considerable
improvement, and 86% ee was obtained (Table 3, entry 3).
However, the more hindered 2-naphthyl derivative could be
converted to the corresponding epoxy ketone in both low yield
and ee. The substituted groups on the phenyl ring of the olefin
side were also investigated under the identical conditions. The
highest ee values were obtained in the epoxidation of o-Br-
substituted chalcone (Table 3, entry 9, 89% ee).
a Reactions were carried out in 1.5 mL of MeCN for 90 min at room
temperature with 0.25 mmol of substrate, 1 mol % complex 6, 6 equiv of
H2O2, and 5 equiv of AcOH. b Epoxide yields determined by GC with an
internal standard. c Determined by GC with a CP-Chirasil-Dex-CB column.
d Isolated yield and ee value are determined by HPLC with a Daicel OD
column.
good epoxidation yields were achieved, and unfunctionalized
olefins such as 6-cyano-2,2-dimethylchromene are generally
(9) (a) Sun, W.; Wang, H. W.; Xia, C. G.; Li, J. W.; Zhao, P. Q. Angew.
Chem., Int. Ed. 2003, 42, 1042. (b) Cheng, Q. G.; Deng, F. G.; Xia, C. G.;
Sun, W. Tetrahedron: Asymmetry 2008, 19, 2359.
(10) Recent examples in asymmetric epoxidation of R,ꢀ-enones: (a) Lu,
X. J.; Liu, Y.; Sun, B. F.; Cindric, B.; Deng, L. J. Am. Chem. Soc. 2008,
130, 8134. (b) Ooi, T.; Ohara, D.; Tamura, M.; Maruoka, K. J. Am. Chem.
Soc. 2004, 126, 6844. (c) Wang, X. W.; Shi, L.; Li, M. X.; Ding, K. L.
Angew. Chem., Int. Ed. 2005, 44, 6362. (d) Li, Y. W.; Liu, X. Y.; Yang,
Y. Q.; Zhao, G. J. Org. Chem. 2007, 72, 288. (e) Nemoto, T.; Ohshima,
T.; Yamaguchi, K.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 2725. (f)
Wang, X. W.; Reisinger, C. M.; List, B. J. Am. Chem. Soc. 2008, 130,
6070. (g) Reisinger, C. M.; Wang, X. W.; List, B. Angew Chem. Int. Ed.
2008, 47, 8112. (h) Lu, J.; Xu, Y. H.; Liu, F.; Loh, T.-P. Tetrahedron Lett.
2008, 49, 6007.
(6) For recent biomimetic asymmetric epoxidation example, see: (a)
Gelalcha, F. G.; Bitterlich, B.; Anilkumar, G.; Tse, M.-K.; Beller, M. Angew.
Chem., Int. Ed. 2007, 46, 7293. (b) Gelalcha, F. G.; Anilkumar, G.; Tse,
M.-K.; Bru¨ckner, A.; Beller, M. Chem.sEur. J. 2008, 14, 7687. (c) Marchi-
Delapierre, C.; Jorge-Robin, A.; Thibon, A.; Me´nage, S. Chem. Commun.
2007, 1166.
(7) Go´mez, L.; Garcia-Bosch, I.; Company, A.; Sala, X.; Fontrodona,
X.; Ribas, X.; Costas, M. Dalton Trans. 2007, 5539.
(8) Guillemot, G.; Neuburger, M.; Pfaltz, A. Chem.sEur. J. 2007, 13,
8960.
3624
Org. Lett., Vol. 11, No. 16, 2009

All these facts clearly indicate that these novel MnII
complexes of chiral N4 ligands are capable of achieving high
enantiomeric excess in the catalytic asymmetric epoxidation.
By comparison of [MnII(R,R-mcp)(CF3SO3)2] and complexes
4-6, it is clear that the size of the C7 and C7′ substituents
is crucial to gain high asymmetric induction. To introduce
proper groups on these positions will tune the steric bulk
and electronic property of the ligands and result in significant
improvement in enantioselectivity.
In summary, we have successfully devised and synthesized
a novel family of chiral Mn(II) complexes of N4 ligands that
exhibit rapid, highly enantioselective epoxidation of various
R,ꢀ-enones under mild conditions. Furthermore, the present
study indicates a conceptual strategy to improve the stereo-
selectivity of biologically inspired oxidation catalysis. Further
studies focus on expanding the scope of this catalytic
asymmetric epoxidation of olefins as well as the development
of even more efficient bioinspired catalysts and on under-
standing the detailed reaction mechanism.
Acknowledgment. We are grateful for financial support
from the Chinese Academy of Sciences and the National
Natural Science Foundation of China (20873166, 20625308).
Supporting Information Available: Experimental pro-
cedures for catalyst synthesis and asymmetric epoxidation
reactions, spectroscopic data for catalysts and products, and
crystallographic data (cif) of complexes 4 and 5. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(11) For detailed procedures for synthesis of the ligands 1-3 and the
corresponding MnII complexes 4-6, see the Supporting Information.
(12) (a) Aldrich-Wright, J. R.; Vagg, R. S.; Williams, P. A. Coord. Chem.
ReV. 1997, 166, 361. (b) Knof, U.; Zelewsky, A. v. Angew. Chem., Int. Ed.
1999, 38, 302.
(13) (a) Fujita, A.; Que, L., Jr. AdV. Synth. Catal. 2004, 346, 190. (b)
Garcia-Bosch, I.; Ribas, X.; Costas, M. AdV. Synth. Catal. 2009, 351, 348.
OL901400M
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