Asymmetric cyclopropanation of styrene with ethyl diazoacetate using a N2P2-ligand ruthenium(II) catalyst: Axial ligand controlled enantioselectivity

Article abstract of DOI:10.1016/S0040-4039(01)00311-2

The N₂P₂-Ru(II) complex 1, activated by silver triflate, exhibited good catalytic activity but low enantioselectivity in the asymmetric cyclopropanation of styrene with ethyl diazoacetate. N-Donor additives were introduced into the a

Full text of DOI:10.1016/S0040-4039(01)00311-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2847–2849
Asymmetric cyclopropanation of styrene with ethyl diazoacetate
using a N2P2-ligand ruthenium(II) catalyst: axial ligand
controlled enantioselectivity
Zhuo Zheng,* Xiaoquan Yao, Chen Li, Huilin Chen and Xinquan Hu
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, PR China
Received 18 December 2000; revised 13 February 2001; accepted 21 February 2001
Abstract—The N2P2–Ru(II) complex 1, activated by silver triflate, exhibited good catalytic activity but low enantioselectivity in
the asymmetric cyclopropanation of styrene with ethyl diazoacetate. N-Donor additives were introduced into the activated system
as axial ligands to improve the ee’s for this reaction. Up to 90% ee for cis-isomers was achieved by using 2,4,6-collidine as an
additive. © 2001 Elsevier Science Ltd. All rights reserved.
Catalytic asymmetric cyclopropanation of olefins with
diazoacetate esters has been one of the most important
methodologies for the formation of chiral cyclopropane
compounds.1 Various optically active N- and N,O-
donor ligands, such as Schiff bases,2 semicorrins,3
bisoxazolines,4 Py-box5 and bipyridines,6 etc., have
been employed successfully in the reaction. However,
there are only a couple of reports on the testing of P-
or N,P-donor ligands in the reaction,7–11 and low ee’s
were observed in most cases. Recently, Noyori reported
the N2P2–Ru(II) complex 1 and employed it as a cata-
lyst precursor in the asymmetric transfer hydrogenation
of aromatic ketones with potassium 2-propoxide as
cocatalyst.12a In this paper, the complex was used as the
catalyst precursor for the asymmetric cyclopropanation
of styrene with ethyl diazoacetate by using AgOTf as
an activating agent and an achiral N-donor additive as
an axial ligand. In the presence of 2,4,6-collidine, up to
90% ee for cis-isomers was achieved.
stable that it cannot be broken during the cyclopropa-
nation to form a coordinatively unsaturated species
catalyzing the decomposition of the diazoacetate ester.
According to the literature method, silver salts, espe-
cially silver triflate, were used as activating agents for
similar catalysts to precipitate out part or all of the
chloride anions.8,13 Therefore, two silver salts, AgOTf
and AgBF4, were used in this reaction to activate the
complex 1, and the results using these activated cata-
lysts are summarized in Table 1.
After being activated by AgOTf, the catalyst showed
very good catalytic activities (entries 2–6 in Table 1
versus entry 1). However, the ee’s were not so high, and
it seemed that the solvents used in the catalyst activa-
tion obviously affected the enantioselectivities of the
cyclopropanation products (entries 2 and 4 versus
entries 3 and 5). Better results were obtained by using 4
equiv. of AgOTf as activating agent, and cis-isomers
were favored in the product. In contrast to the use of
AgOTf as an activating agent, AgBF4 gave a 70% ee,
but the chemical yield was only 7%.
Cl
N
N
It is well known that some N-donor additives can
improve enantioselectivity in asymmetric cyclopropana-
tion catalyzed by the salen/salen-like ligand–metal com-
plexes.14,15 Herein, we also tried to introduce some
N-donor additives into the activated catalyst system as
axial ligands. The results are listed in Table 2.
The N2P2-Ru(II) Complex 1
Ru
Cl
P
Ph2
P
Ph2
In the distorted octahedral structure of the N2P2–Ru(II)
complex 1,12 the RuꢀCl bond in the axial position is so
Et3N was used in our initial attempt, which resulted in
a remarkable improvement of the ee’s. Using 6 or 12
equiv. of Et3N, about 80% ee for cis-isomers was
achieved at room temperature.
* Corresponding author. Tel.: +86+411-4671991-712; fax: +86+411-
4684746; e-mail: zhengz@ms.dicp.ac.cn
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00311-2

2848
Z. Zheng et al. / Tetrahedron Letters 42 (2001) 2847–2849
Table 1. Asymmetric cyclopropanation of styrene with ethyl diazoacetate using AgOTf or AgBF4 as an activating agenta
Ph
H
H
H
H
Ph
Cat.
N2CHCO2Et
+
+
CO2Et
Ph
CO2Et
trans
cis
Entry
Additive
Ag:Ru
Solvent
Temp. (°C)
Yieldb (%)
cis:transd
% eec,d (cis)
% eec,e (trans)
1
2
3
4
5
6
7
–
–
–
25
25
25
25
25
0
0
95
98
97
97
69
7
–
–
0
10
0
40
51
70
–
0
17
0
5
31
0
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgBF4
2:1
2:1
4:1
4:1
4:1
4:1
CH2Cl2
CH2Cl2/styrene
CH2Cl2
CH2Cl2/styrene
CH2Cl2/styrene
CH2Cl2/styrene
55:45
57:43
60:40
62:38
60:40
88:12
25
a Complex 1 (83 mg, 0.01 mmol) and 2 or 4 equiv. of AgOTf were mixed with 2 mL of CH2Cl2 and with (or without) 2 mL of styrene in a 25
mL Schlenk tube. The mixture was stirred at room temperature overnight, and then, the precipitate was filtered off. Ethyl diazoacetate (57 mg,
0.5 mmol) in 5 mL of CH2Cl2 was added to the solution containing the catalyst and styrene at the selected temperature in 6 h by a syringe pump
and stirred for another 8 h. The catalyst-free sample was analyzed by GC.
b Determined by GC with diethyl adipate as internal standard.
c The ee’s for the cyclopropanation product and the ratio of trans- and cis-isomers were determined by capillary GC using a chiral column
(cyclodex-b, 2,3,6-M, 30 m×0.25 mm i.d.), and the configuration of the four isomers was determined by comparing the GC elution order with
authentic sample prepared according to the literature.
d 1R,2S as the major enantiomer.
e 1R,2R as the major enantiomer.
Table 2. Asymmetric cyclopropanation of styrene with ethyl diazoacetate in the presence of some N-donor additivesa,b
Entry
Additive
Additive:Ru (mol/mol)
Temp. (°C)
Yield (%)
cis:trans
% ee (cis)c
% ee (trans)d
1
2
3
4
5
6
7
8
Et3N
Et3N
Et3N
Et3N
2-Picoline
2,6-Lutidine
2,4,6-Collidine
2,4,6-Collidine
2:1
6:1
25
25
25
25
25
25
25
0
25
25
25
25
25
25
25
67
49
40
41
8
50
81
55
61
42
53
0
60:40
69:31
76:24
61:39
62:38
70:30
70:30
64:36
73:27
57:43
77:23
–
47
80
81
68
71
79
82
90
14
63
84
–
13
46
34
10
11
70
79
73
33
68
26
–
12:1
24:1
12:1
12:1
12:1
12:1
9
2,6-Dichloropyridine 12:1
10
11
12
13
14
15
2-Chloro-6-picoline
2-Bromopyridine
3-Bromopyridine
Imidazole
N-Methylimidazole
Pyridine
12:1
12:1
12:1
12:1
12:1
12:1
0
–
–
–
–
–
–
–
–
–
Trace
0
a Reaction conditions: 0.5 mmol of ethyl diazoacetate, 2 mL of styrene, 2 mol% catalyst prepared in situ (based on the diazoacetate), and 12 equiv.
of additive were added.
b The exchange of Cl/OTf was carried out in 2 mL of CH2Cl2 at 25°C. Then, the precipitate was filtered off, and the selected additive was
introduced into the solution and stirred for 2 h.
c 1R,2S as the major enantiomer.
d 1R,2R as the major enantiomer.
Under the optimum reaction conditions, based on Et3N
as an additive, other N-donor additives, including imi-
dazole, N-methyl imidazole and a series of pyridine
derivatives, were examined.
attempted in the presence of 2,4,6-collidine, and a good
ee, up to 90% for the cis-isomers, was achieved (entry
8).
In summary, we have reported an effective catalyst
system for the asymmetric cyclopropanation of styrene
and ethyl diazoacetate using the N2P2–Ru(II) complex
1 as precursor. After being activated by AgOTf, good
catalytic activities were observed. With the introduction
of some N-donor additives as axial ligands, good enan-
tioselectivity of the reaction (around 80–90% ee) was
achieved.
As shown in entries 5–15, the ee’s of around 80–85%
are obtained by using 2,6-lutidine, 2,4,6-collidine and
a-bromopyridine as additives, while imidazole, N-
methylimidazole, pyridine and 3-bromopyridine cause
the deactivation of the catalyst. Among the additives,
2,4,6-collidine gave a fairly high yield at room tempera-
ture (81% yield, entry 7). Lower temperature, 0°C, was

Z. Zheng et al. / Tetrahedron Letters 42 (2001) 2847–2849
2849
Acknowledgements
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The authors would like to thank the National Natural
Science Foundation of China for financial support of
this work (29933050) and also thank Professor Jingxin
Gao for his helpful discussion.
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