Substituted salen-Ru(II) complexes as catalysts in the asymmetric cyclopropanation of styrene by ethyl diazoacetate: The influence of substituents and achiral additives on activity and enantioselectivity

Article abstract of DOI:10.1016/S0957-4166(01)00014-3

A series of alkyl-, halogen- and nitro-substituted salen ligands, 1, have been employed in the asymmetric cyclopropanation of styrene with ethyl diazoacetate by its ruthenium(II) complex with [RuCl₂(p-cymene)]₂ or RuCl₂(PP

Full text of DOI:10.1016/S0957-4166(01)00014-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 197–204
Substituted salen–Ru(II) complexes as catalysts in the
asymmetric cyclopropanation of styrene by ethyl diazoacetate:
the influence of substituents and achiral additives on activity and
enantioselectivity
Xiaoquan Yao, Min Qiu, Weiran Lu¨, Huilin Chen and Zhuo Zheng*
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, PR China
Received 11 August 2000; accepted 4 January 2001
Abstract—A series of alkyl-, halogen- and nitro-substituted salen ligands, 1, have been employed in the asymmetric cyclopropa-
nation of styrene with ethyl diazoacetate by its ruthenium(II) complex with [RuCl2(p-cymene)]2 or RuCl2(PPh3)3 as precursors.
The introduction of appropriate electron withdrawing groups in the salen ligands benefited the enantioselectivity of the reaction.
Some additives, including O-donor, N-donor and P-donor ligands, were added to the reaction to improve the enantioselectivity
and activity, and e.e.s of up to 80% were achieved. In the salen/[RuCl2(p-cymene)]2 system, the (1R,2S)-isomer was obtained in
80.2% e.e. by using the salen ligand 1f derived from 3,5-dibrominated salicylaldehyde with Et3N as additive. E.e.s of up to 81.3%
for (1S,2R)-isomers were achieved by using the complex 2 synthesized from the nitro-substituted ligand 1m and RuCl2(PPh3)3. A
possible mechanism was also discussed. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
metric cyclopropanation of styrene by tert-butyl dia-
zoacetate.14,15
Catalytic asymmetric cyclopropanation of olefins with
diazoacetate esters has been one of the most important
methodologies for the formation of chiral cyclopropane
compounds.1 Catalysts containing various metals and
optically active ligands, such as Cu–Schiff bases,2 Co–
dioximate,3 and complexes with C2 symmetry including
Cu–semicorrin,4 Cu–bisoxazoline,5 Cu–bipyridine,6
Rh2(5S-MEPY),7 etc., have been employed successfully.
Although copper–Schiff base complexes have a long
history of use in the reaction, the optically active salen
ligands derived from (R,R)-trans-1,2-diaminocyclohex-
ane and salicylaldehydes were exceptional in several
asymmetric processes including epoxidation,8 epoxide
opening,9 kinetic resolution,10 Diels–Alder cycloaddi-
tion11 and the trimethylsilylcyanation of aldehydes,12
and proved to be uniformly ineffective for asymmetric
alkene aziridination and cyclopropanation when using
their copper(II) complexes.13 Recently, however, the
salen–Co(III) complexes, using 1,2-diphenylethylenedi-
amine as the chiral source, were reported by Fukuda
and Katsuki, and a salen-like Co(II) complex, MPAC,
by Yamada et al., to be efficient catalysts in the asym-
Among all the catalysts reported, the Ru(II) complexes
have attracted more and more attention in recent years.
Ru–Pybox16 and Ru–porphyrin17 have been successfully
employed in the asymmetric cyclopropanation of sty-
rene and diazoacetate. Very recently, Katsuki et al. also
reported a chiral (NO)–salen–Ru complex derived from
(R,R)-1,2-diaminocyclohexane and (aR)-3-formyl-2-
hydroxy-2%-phenyl-1,1%-binaphthyl, which effectively
catalyzed the asymmetric cyclopropanation of styrene
by tert-butyl diazoacetate with high cis- and enantiose-
lectivity.18 It is also noteworthy that solubility depen-
dent enantiofacial selection was observed by using THF
and hexane as solvents, respectively.18b The same lig-
ands have also been employed in the Co(II)-catalyzed
asymmetric cyclopropanation.18d
In our previous studies, some modified Aratani’s cata-
lysts derived from halogen- or nitro-substituted salicyl-
aldehydes were reported.19 The introduction of elec-
tron-withdrawing groups to the ligands clearly
improved the enantioselectivity for the asymmetric
cyclopropanation of styrene with ethyl diazoacetate.
Herein, we report a series of alkyl-, halogen- and
nitro-substituted salen ligands 1, derived from the cor-
responding substituted salicylaldehydes and (R,R)-1,2-
* Corresponding author. Tel.: +86+411-4671991-712; fax: +86+411-
4684746; e-mail: zhengz@ms.dicp.ac.cn
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00014-3

198
X. Yao et al. / Tetrahedron: Asymmetry 12 (2001) 197–204
diaminocyclohexane, and their utility in the asymmetric
cyclopropanation of styrene with ethyl diazoacetate by
their ruthenium(II) complexes formed in situ (Scheme
1). Two ruthenium(II) precursors, [RuCl2(p-cymene)]2
and RuCl2(PPh3)3, were used. At present with some of
the additives, e.e.s of around 80% were achieved.
ligand 1e or 1h were substituted by a halogen atom, the
catalytic activity improved, but lower enantioselectivity
was observed (entries 6 and 9).
Considering the octahedral coordination structure of
the saturated Ru(II)–salen complexes, we suspected
that there might be two iso-propanol molecules in the
catalyst prepared in situ from 1 and [RuCl2(p-cymene)]2
in iso-propanol. In fact, a similar example has been
reported for the salen–Co(III) complex catalyst system
by Katsuki, in which the authors noted that the pres-
ence of methanol improved the observed enantioselec-
tivity.14a Therefore, other alcohols and some non-protic
solvents were tried by using the ligand 1e as a proto-
type. The results of these reactions are summarized in
Table 2.
2. Results and discussion
Initially, the classic salen ligand 1a was tested. The
salen–Ru(II) complexes were prepared by mixing
[RuCl2(p-cymene)]2 with a small excess of ligand and 2
equivalents of Et3N in iso-propanol. Poor yields and
enantioselectivities were observed (entry 1 in Table 1).
Other less hindered alkyl-substituted ligands, 1b–1d,
were subsequently tested. Some asymmetric induction
was observed (entries 2–4 in Table 1). In contrast to the
asymmetric epoxidation of simple olefins, in which the
bulky alkyl substituents at C(3) and C(3%) have a posi-
tive effect on the enantiocontrol of the reaction,20 these
results suggested that bulky alkyl substituents at C(3)
and C(3%) were detrimental to the enantioselectivity and
yield of the reaction.
It can be seen from Table 2 that both enantioselectivity
and catalytic activity were markedly influenced by the
addition of alcohols (entry 1 versus entries 3–5 in Table
2). The bulky alkyl alcohols were beneficial to the
enantioselectivity, but yields decreased slightly (entries
3–5). When L-menthol was used as an additive, moder-
ate e.e.s and yield were obtained. It is also noteworthy
that the configuration of the cis isomers and the ratio of
cis/trans became inverted when THF was used as the
solvent.
In our previous studies,19 the introduction of electron
withdrawing groups to the modified Aratani’s catalysts
improved the enantioselectivity of the asymmetric
cyclopropanation. In the Ru(II)–Pybox-catalyzed sys-
tem, the electron withdrawing groups also proved to
enhance catalytic activity and enantioselectivity.21 The
series of halo- and nitro-substituted salen ligands 1e–1m
were evaluated in the reaction.
It is well known that some N-donor additives can
improve the enantioselectivity in the asymmetric cyclo-
propanation catalyzed by the salen (or salen-like) metal
complexes.15,18 Herein, we also tried to introduce some
N-donor additives into the reaction as axial ligands by
using excess base in the catalyst preparation; Et3N was
used initially, as shown in Table 3.
As can be seen from the data in Table 1, the introduc-
tion of halogen atoms at C(3) and C(3%) benefited the
enantioselectivity and catalytic activity. The ligand 1e,
bearing a bromine atom at C(3) and C(3%) and tert-
butyl at C(5) and C(5%), was employed at room temper-
ature, and increased enantioselectivity from an e.e. of
33.3 to 74.2% for the trans isomers compared with the
ligand 1d (entry 5 versus entry 4). Correspondingly, the
chloro-substituted ligand 1h gave an e.e. of 61.4%.
When the bulky alkyl substituents at C(5) and C(5%) in
In the salen/[RuCl2(p-cymene)]2/Et3N system, the bulky
alkyl group at C(3) and C(3%) proved to be unfavorable
to enantioselectivity and activity, and only a substituent
with the appropriate size and electron withdrawing
effect at C(3) and C(3%) favored the enantiocontrol of
the cyclopropanation. In contrast to the trend observed
in Table 1, the best result, with respect to both e.e. and
yield, was achieved when ligand 1f, derived from 3,5-
Scheme 1.

X. Yao et al. / Tetrahedron: Asymmetry 12 (2001) 197–204
199
Table 1. The asymmetric cyclopropanation of styrene with ethyl diazoacetate using [RuCl2(p-cymene)]2 as catalyst precursora
Entry
Ligand
Yield (%)b
cis/transc
% e.e. (cis)c,d
% e.e. (trans)c,e
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
15
51
43
41
58
78
57
57
74
55
40
82
52
34:66
32:68
24:76
34:66
14:86
24:76
26:74
22:78
24:76
34:66
20:80
26:74
29:71
0
12.9
38.2
44.0
33.3
74.2
35.6
57.8
61.4
41.9
45.0
38.8
42.8
30.3
54.5
52.3
49.0
60.6
36.2
58.5
45.8
40.9
58.4
19.2
43.6
24.5
9
10
11
12
13
1j
1k
1l
1m
a Reaction conditions: 1 mmol of ethyl diazoacetate, 10 mmol of styrene, 2% catalyst prepared in situ (based on the diazoacetate), 3.0 mL of
CH2Cl2, room temperature.
b Determined by GC with diethyl adipate as internal standard.
c The e.e.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-methylated, 30 m×0.25 mm i.d.), and the configuration of the four isomers was determined by comparing the GC elution order
with an authentic sample prepared according to the literature.2
d (1R,2S) as the major enantiomer.
e (1R,2R) as the major enantiomer.
Table 2. The influence of the additives on the asymmetric cyclopropanation of styrene with ethyl diazoacetate using ligand
1ea
Entry
Solvent or additiveb
Yield (%)c
cis/transd
% e.e. (cis)e,f
% e.e. (trans)
1g
2h
3
CH2Cl2/styrene
THF
EtOH
i-PrOH
tert-BuOH
58
68
77
58
58
72
21:79
62:38
20:80
14:86
26:74
18:72
33.8
−26.9
33.0
60.6
67.7
53.2
2.8
22.5
74.2
49.7
68.8
4
5
6i
L-Menthol
46.8
a Reaction conditions: 1 mmol of ethyl diazoacetate, 10 mmol of styrene, 2% catalyst prepared in situ (based on the diazoacetate), 3.0 mL of
CH2Cl2, room temperature.
b The alcohols were added in the process of the preparation of the catalysts as solvents except entry 5.
c Determined by GC with diethyl adipate as internal standard.
d The e.e.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-methylated, 30 m×0.25 mm i.d.), and the configuration of the four isomers was determined by comparing the GC elution order
with an authentic sample prepared according to the literature.12
e (1R,2S) as the major enantiomer, except (1S,2R) was the major enantiomer in entry 2.
f (1R,2R) as the major enantiomer.
g The catalyst was prepared in situ in 5 mL of CH2Cl2/styrene (1:1), 2 equiv. Et3N were added as base, and the solution was stirred at room
temperature for 4 hours.
h The catalyst was prepared in situ in 3 mL THF, 2 equiv. Et3N were added as base, and the solution was stirred at room temperature for 4 hours.
i The catalyst was prepared in situ in 3 mL of CH2Cl2, 6 equiv. of
L-menthol and 2 equiv. of Et3N were added, and the solution was stirred at
room temperature for 4 hours. 12 equiv. of
L-menthol was also tried, but there was no obvious difference observed.
ture further to −15°C but the yield of the reaction
lowered to 68% (entries 8, 9 in Table 3).
dibrominated salicylaldehyde, was used. This gave e.e.
of only 35% without excess Et3N present. E.e.s of
around 70% and a 98% yield were obtained at room
temperature with Et3N present (entry 7 in Table 3
versus entry 6 in Table 1). When the reaction was
carried out at 0°C, better enantioselectivity was
observed with a slightly decreased yield. E.e.s of up to
80.2% were achieved by reducing the reaction tempera-
Examining the results shown in Table 3, the addition of
Et3N resulted in a marked decrease in the catalytic
activity, except for the dihalo-substituted ligands 1f and
1i. Higher reaction temperature was tried for the low
activity catalysts using the ligand 1e as a prototype; this

200
X. Yao et al. / Tetrahedron: Asymmetry 12 (2001) 197–204
By using RuCl2(PPh3)3 as a precursor, similar results
were observed for the halogen-substituted ligands 1e–1j
to those obtained in salen/[Ru(p-cymene)Cl2]2 systems.
However, it was surprising that e.e.s of up to 81.3% for
(1S)-isomers and a yield of greater than 90% was
achieved by using the nitro-substituted ligand 1m, while
only poor e.e.s were observed for the opposite (1R)-iso-
mers when [Ru(p-cymene)Cl2]2 was used as the precur-
sor (entry 9 in Table 5 versus entry 13 in Table 1 and
entry 16 in Table 3). Correspondingly, the other two
nitro-substituted ligands 1k and 1l also give better
enantioselectivities for (1S)-isomers in this system.
Scheme 2.
The abnormal enantioselectivity caused by the intro-
duction of PPh3 as an axial ligand led us to investigate
the effect of variation of reaction temperature on the
behavior of ligand 1m, and it was found that a higher
yield was obtained from reaction at 0°C compared to
35°C (entries 10, 11). We also attempted to add 1 equiv.
of PPh3 into the catalyst prepared in situ from 1m and
[RuCl2(p-cymene)]2 in CH2Cl2/styrene but far lower
catalytic activity and e.e.s for (1S)-isomers were
obtained (entry 12). The preliminary in situ tempera-
ture variation 31P NMR study showed that there was
no free PPh3 observed in the system from −40 to 25°C.
We suspect that the coordinatively unsaturated species
in the reaction catalyzed by complex 2 might not be
formed by the isolation of PPh3 in the axial position,
but by the breakage of an NꢀRu bond, which might
result in a chiral environment favoring (1S)-isomers.
resulted in improved catalytic activity, but regio- and
enantioselectivity were changed unfavorably (entry 2 in
Table 3).
Other bases, including n-Bu3N, pyridine, 2,6-lutidine
and DMAP, were also employed for ligand 1e. Et3N
gave the best result in enantioselectivity, while 2,6-
lutidine gave a far higher activity than the others, but
with poor e.e.s (Table 4).
As a new attempt, the P-donor axial ligand was also
employed by using RuCl2(PPh3)3 as a precursor. The
free triphenylphosphine ligand released during the coor-
dination of 1 with Ru(II) precursor must be removed
before introducing the styrene and dichloromethane.22
The structure of the catalysts formed in situ was con-
firmed by the isolated complex 2, which was prepared
from RuCl2(PPh3)3 and ligand 1m, and easily isolated
from the iso-propanol solution as a stable crystal in air
(Scheme 2). It was characterized by NMR and ESI MS,
and should have the structure described in Scheme 2, in
which there are two PPh3 molecules occupying the axial
position. The results of 1e–1m are listed in Table 5.
3. Conclusion
In summary, for the salen–Ru(II)-catalyzed asymmetric
cyclopropanation system, the substituents on the salicyl-
Table 3. The influence of Et3N on the asymmetric cyclopropanation of styrene with ethyl diazoacetate using the substituted
salen ligands 1a–1ka
Entry
Ligand
Additiveb
Temp. (°C)
Yield (%)
cis:trans
% e.e. (cis)c
% e.e. (trans)d
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1e
1f
1f
1f
1g
1h
1i
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Rt
Rt
Rt
Rt
Rt
35
23
24
28
24
35
60
98
91
68
36
37
61
41
35
79
29
35:65
31:69
24:76
28:72
29:71
68:32
25:75
23:77
22:78
29:71
27:73
24:76
32:68
19:81
27:73
31:69
–
–
33.7
37.6
29.0
42.9
42.9
68.2
78.4
80.2
33.4
11.0
51.5
49.6
32.9
21.9
16.0
23.7
31.0
13.6
55.0
47.2
60.0
69.1
65.4
31.4
36.5
44.8
32.6
48.1
24.2
17.6
Rt
0
9
−15
Rt
Rt
Rt
Rt
Rt
Rt
Rt
10
11
12
13
14
15
16
1j
1k
1l
1m
a Reaction conditions: 1 mmol of ethyl diazoacetate, 10 mmol of styrene, 2% catalyst prepared in situ (based on the diazoacetate), 3.0 mL of
CH2Cl2, at the selected temperature.
b 6 equiv. of base (based on the ruthenium(II) precursor) were added as additive in the procedure of the preparation of the catalyst in situ.
c (1R,2S) as the major enantiomer.
d (1R,2R) as the major enantiomer.

X. Yao et al. / Tetrahedron: Asymmetry 12 (2001) 197–204
201
Table 4. The influence of the additives on the asymmetric cyclopropanation of styrene with ethyl diazoacetate using ligand
1ea
Entry
Additiveb
Temp. (°C)
Yield (%)
cis:trans
% e.e. (cis)c
% e.e. (trans)d
1
2
3
4
5
Et3N
35
35
35
35
35
60
34
39
82
68:32
40:60
43:57
22:78
–
42.9
3.6
17.0
22.0
–
47.2
33.5
5.0
11.2
–
n-Bu3N
Pyridine
2,6-Lutidine
DMAP
Trace
a Reaction conditions: 1 mmol of ethyl diazoacetate, 10 mmol of styrene, 2% catalyst prepared in situ (based on the diazoacetate), 3.0 mL of
CH2Cl2.
b 6 equiv. of the bases (based on the ruthenium(II) precursor) were added in the preparation of the catalyst in situ, except entry 2, where 4
equivalents of DMAP were added.
c (1R,2S) as the major enantiomer.
d (1R,2R) as the major enantiomer.
Table 5. Asymmetric cyclopropanation of styrene with ethyl diazoacetate using RuCl2(PPh3)3 as precursora
Entry
Ligand
Temp. (°C)
Yield (%)
cis:trans
% e.e. (cis)b
% e.e. (trans)c
1
2
3
4
5
6
7
8
1e
1f
1g
1h
1i
1j
1k
1l
1m
1m
1m
1m
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
0
57
56
44
58
54
54
66
87
92
87
77
24
24:76
25:75
36:64
25:75
28:72
35:65
24:76
21:79
43:57
44:56
42:58
39:61
59.0
29.6
13.5
49.0
41.6
51.8
28.4
13.7
37.2
38.1
28.8
22.3
−7.9
−15.3
−79.7
−73.2
−53.1
−10.4
−5.5
−18.4
−81.3
−54.7
−60.2
−18.8
9
10
11
12d
35
Rt
a Reaction conditions: 1 mmol of ethyl diazoacetate, 10 mmol of styrene, 2% catalyst prepared in situ (based on the diazoacetate), 3.0 mL of
CH2Cl2, room temperature.
b (1R,2S) as the major enantiomer except (1S,2R) as the major enantiomer in entry 7.
c (1R,2R) as the major enantiomer except (1S,2S) as the major enantiomer in entry 7.
d The catalyst was prepared in situ in 5 mL of CH2Cl2/styrene (1:1); 2 equiv. Et3N were added as base. The mixture was stirred at room
temperature for 4 hours, and then 1 equiv. of PPh3 was added and the mixture stirred for another 4 hours.
aldehyde are of great importance to the enantioselectiv-
ity observed. Bulky alkyl substituents at C(3) and C(3%)
disfavored the enantioselectivity in the asymmetric
cyclopropanation. With the introduction of electron
withdrawing groups, enantioselectivity improved. The
enantioselectivity and activity were also affected dra-
matically by the presence of additives. E.e.s of up to
80.2% for the (1R,2S)-isomer were achieved by using
ligand 1f derived from 3,5-dibromosalicylaldehyde in
the salen/[Ru(p-cymene)Cl2]2 system with Et3N as an
additive. By using RuCl2(PPh3)3 as a precursor, the
ligand 1m gave e.e.s of around 80% for (1S)-isomers of
ethyl 2-phenylcyclopropanecarboxylate.
rected. Nuclear magnetic resonance spectra were
recorded with a Bruker DRX-400 (400 MHz). Optical
rotations were measured on a JASCO-1020. GC analy-
sis was performed using an HP-4890D. ESI MS spectra
were recorded with an HP1100 LC/MSD. The ligand
1m and complex 2 were the original compounds and
ligands 1a–1l have been previously reported.
4.1. Ligand preparation: general procedure for the
synthesis of ligands 1a–1k and 1m
In a 50 mL Schlenk flask, (R,R)-1,2-diammoniumcyclo-
hexane mono-(+)-tartrate salt (1 mmol), K2CO3 (2
mmol) and distilled water (5 mL) were added. The
mixture was stirred until dissolution, and then 20 mL
ethanol was added. The resulting mixture was heated to
reflux, and a solution of substituted salicylaldehyde (2
mmol) in ethanol (10 mL) was added over a period of
30 minutes, and then stirred under reflux for 2 hours.
After the resulting mixture was cooled to 0°C, water (10
mL) was added slowly and the temperature was main-
tained below 5°C overnight. The product was collected
by filtration and washed with ethanol (5 mL). The
4. Experimental
All reactions were carried out under an inert argon
atmosphere. Iso-propanol was refluxed with sodium
and
distilled
under
argon
atmosphere.
Dichloromethane was distilled from CaH2. Styrene was
freshly distilled and degassed with argon. Melting
points were taken using a Yazawz BY-1 and are uncor-

202
X. Yao et al. / Tetrahedron: Asymmetry 12 (2001) 197–204
crude solid was redissolved in 20 mL CH2Cl2, washed
with water (2×10 mL) and brine (15 mL). After drying
over Na2SO4, the solvent was removed under vacuum,
and the product was isolated as a yellow powder.
(s, 2H), 7.37 (d, J=2.0 Hz, 2H), 7.06 (d, J=2.0 Hz,
2H), 3.34–3.32 (m, 2H), 2.0–1.4 (m, 8H), 1.23 (s, 18H);
13C NMR: 164.6, 154.9, 141.8, 130.0, 126.6, 120.8,
118.5, 72.4, 34.0, 33.0, 31.2, 24.0.
4.1.1. (R,R)-N,N%-Bis(3,5-di-tert-butyl-salicylidene)-1,2-
cyclohexanediamine 1a. Mp 202–203°C; [h]2D0=−309 (c
4.1.9.
(R,R)-N,N%-Bis(3,5-di-chloro-salicylidene)-1,2-
cyclohexanediamine 1i. Mp 139–141°C; [h]2D0=−371 (c 1,
1
1
1, CH2Cl2); H NMR (DCCl3) l 13.77 (s, 2H), 8.34 (s,
CH2Cl2); H NMR (DCCl3) l 14.20 (s, 2H), 8.18 (s,
2H), 7.34 (d, J=2.2 Hz, 2H), 7.02 (d, J=2.2 Hz, 2H),
3.70–3.30 (m, 2H), 2.0–1.4 (m, 8H), 1.44 (s, 18H), 1.27
(s, 18H); 13C NMR: 165.9, 158.1, 139.9, 136.4, 126.8,
117.9, 72.4, 35.0, 34.1, 33.3, 29.5, 24.4.
2H), 7.34 (s, 2H), 7.07 (s, 2H), 3.37–3.33 (m, 2H),
2.0–1.4 (m, 8H); 13C NMR: 163.3, 156.2, 132.2, 129.1,
122.8, 122.5, 119.1, 72.1, 32.8, 23.8.
4.1.10. (R,R)-N,N%-Bis(5-chloro-salicylidene)-1,2-cyclo-
hexanediamine 1j. Mp 191°C; [h]2D0=−199 (c 1, CH2Cl2);
1H NMR (DCCl3) l 13.22 (s, 2H), 8.14 (s, 2H), 7.17
(dd, J=2.3 Hz, 8.8 Hz, 2H), 7.09 (d, J=1.4 Hz, 2H),
6.83 (d, J=8.8 Hz, 2H), 3.30–3.24 (m, 2H), 1.9–1.4 (m,
8H); 13C NMR: 163.5, 159.4, 132.0, 130.4, 123.1, 119.2,
118.3, 72.5, 32.8, 23.9.
4.1.2.
(R,R)-N,N%-Bis-salicylidene-1,2-cyclohexanedi-
1
amine 1b. Mp 59–60°C; [h]2D0=−394 (c 1, CH2Cl2); H
NMR (DCCl3) l 13.02 (s, 2H), 8.24 (s, 2H), 7.24–7.20
(m, 2H), 7.13 (dd, J=1.6 Hz, 7.7 Hz, 2H), 6.88 (d,
J=8.2 Hz, 2H), 6.89–6.76 (m, 2H), 3.30–3.28 (m, 2H),
1.9–1.4 (m, 8H); 13C NMR: 164.6, 160.9, 132.1, 131.4,
118.5, 116.7, 72.5, 33.0, 24.1.
4.1.11. (R,R)-N,N%-Bis(3-nitro-5-tert-butyl-salicylidene)-
1,2-cyclohexanediamine 1k. Mp 105–106°C; [h]2D0=−566
4.1.3.
(R,R)-N,N%-Bis(3,5-di-methyl-salicylidene)-1,2-
1
cyclohexanediamine 1c. Mp 105–107°C; [h]2D0=−384 (c
(c 1, CH2Cl2); H NMR (DCCl3) l 15.10 (s, 2H), 8.38
1
1, CH2Cl2); H NMR (DCCl3) l 13.38 (s, 1H), 8.18 (s,
(s, 2H), 8.05 (d, J=2.4 Hz, 2H), 7.46 (d, J=2.4 Hz,
2H), 3.48–3.41 (m, 2H), 2.0–1.4 (m, 8H) 1.27 (s, 18H);
13C NMR: 164.9, 155.8, 140.3, 137.4, 134.4, 126.6,
119.8, 71.5, 34.1, 32.8, 30.9, 23.9.
1H), 6.92 (s, 2H), 6.77 (s, 2H), 3.28–3.25 (m, 2H), 2.20
(s, 6H), 2.17 (s, 6H), 1.9–1.4 (m, 8H); 13C NMR: 164.7,
156.9, 134.1, 129.1, 126.9, 125.2, 117.5, 72.6, 33.1, 24.1,
20.2, 15.3.
4.1.12. Preparation of (R,R)-N,N%-bis(3,5-di-nitro-sali-
cylidene)-1,2-cyclohexanediamine 1l. In a 50 mL Schlenk
flask, (R,R)-1,2-diammoniumcyclohexane (1 mmol) was
dissolved in ethanol (10 mL). The solution was heated
under reflux, and a solution of 3,5-dinitrosalicylalde-
hyde (2 mmol) in ethanol (10 mL) was added over a
period of 30 minutes; the reaction mixture was then
stirred under reflux for 2 hours. The mixture was
cooled to room temperature. The crystalline product
was collected and washed with ethanol (5 mL) and
diethyl ether (5 mL), affording product 1l as orange
crystalline powder (85% yield). Mp 248–249°C; [h]2D0=
4.1.4.
(R,R)-N,N%-Bis(5-tert-butyl-salicylidene)-1,2-
cyclohexanediamine 1d. Mp 116–118°C; [h]2D0=−179 (c
1
1, CH2Cl2); H NMR (DCCl3) l 13.14 (s, 2H), 8.26 (s,
2H), 7.27 (dd, J=1.3 Hz, 8.7 Hz, 2H), 7.12 (s, 2H), 6.82
(d, J=8.7 Hz, 2H), 3.30–3.28 (m, 2H), 1.9–1.4 (m, 8H),
1.23 (s, 18H); 13C NMR: 164.9, 158.6, 141.1, 129.4,
127.9, 117.9, 116.2, 72.7, 33.8, 33.1, 31.3, 24.1.
4.1.5. (R,R)-N,N%-Bis(3-bromo-5-tert-butyl-salicylidene)-
1,2-cyclohexanediamine 1e. Mp 197–200°C; [h]2D0=−309
(c 1, CH2Cl2); H NMR (DCCl3) l 14.17 (s, 2H), 8.22
(s, 2H), 7.53 (s, 2H), 7.10 (d, J=1.3 Hz, 2H), 3.34–3.29
(m, 2H), 1.9–1.4 (m, 8H), 1.25 (s, 18H); 13C NMR:
164.5, 155.8, 142.3, 132.9, 127.4, 118.3, 110.6, 72.2,
34.0, 32.9, 31.2, 24.0.
1
1
−148 (c 1, DMSO); H NMR (DMSO-d6) l 13.56 (s,
2H), 8.92 (s, 2H), 8.76 (d, J=3.42 Hz, 2H), 8.66 (d,
J=3.42 Hz, 2H), 4.26–4.24 (m, 2H), 2.1–1.0 (m, 8H);
13C NMR: 169.7, 167.7, 140.7, 137.6, 129.9, 127.5,
117.2, 63.3, 30.7, 23.4.
4.1.6.
(R,R)-N,N%-Bis(3,5-di-bromo-salicylidene)-1,2-
cyclohexanediamine 1f. Mp 140–142°C; [h]2D0=−267 (c
4.1.13.
(R,R)-N,N%-Bis(5-nitro-salicylidene)-1,2-cyclo-
1
1, CH2Cl2); H NMR (DCCl3) l 14.32 (s, 2H), 8.14 (s,
hexanediamine 1m. Mp 219–221°C; [h]2D0=−20.9 (c 1,
1
2H), 7.64 (s, 2H), 7.24 (s, 2H), 3.37–3.35 (m, 2H),
2.0–1.4 (m, 8H); 13C NMR: 163.2, 157.8, 137.7, 132.9,
119.6, 112.1, 109.7, 71.9, 32.8, 23.8, 18.4.
CH2Cl2); H NMR (DCCl3) l 14.32 (s, 2H), 8.36 (s,
2H), 8.15–8.12 (m, 4H), 6.93 (d, J=8.9 Hz, 2H), 3.52–
3.45 (m, 2H), 2.05–1.50 (m, 8H); 13C NMR: 167.5,
163.7, 139.3, 128.0, 127.9, 118.3, 117.0, 71.7, 32.6, 23.8.
Anal. calcd for C20H20N4O6: C, 58.25; H, 4.89; N,
13.59; O, 23.58. Found: C, 58.53; H, 4.96; N, 13.77%.
4.1.7. (R,R)-N,N%-Bis(5-bromo-salicylidene)-1,2-cyclo-
hexanediamine 1g. Mp 189–190°C; [h]2D0=−99 (c 1,
CH2Cl2); H NMR (DCCl3) l 13.24 (s, 2H), 8.15 (s,
1
2H), 7.31 (dd, J=2.2 Hz, 8.8 Hz, 2H), 7.25 (d, J=8.8
Hz, 2H), 6.79 (d, 2H), 3.30–3.28 (m, 2H), 1.9–1.4 (m,
8H); 13C NMR: 163.4, 159.9, 134.9, 133.4, 119.8, 118.8,
110.0, 72.5, 32.8, 24.0.
4.2. Preparation of catalyst 2
In a 50 mL Schlenk flask, Ru(PPh3)Cl2 (0.2206 g, 0.230
mmol) was mixed with the ligand 1m (0.1000 g, 0.242
mmol) in iso-propanol (15 mL); Et3N (0.192 mL, 6
equiv.) was then added. The solution was stirred under
reflux for two hours, then cooled to room temperature.
The crystalline product was collected and recrystallized
4.1.8. (R,R)-N,N%-Bis(3-chloro-5-tert-butyl-salicylidene)-
1,2-cyclohexanediamine 1h. Mp 209–212°C; [h]2D0=−266
1
(c 1, CH2Cl2); H NMR (DCCl3) l 14.14 (s, 2H), 8.25

X. Yao et al. / Tetrahedron: Asymmetry 12 (2001) 197–204
203
from CH2Cl2 and hexane (1:6), affording 0.1935 g of
Wiley: New York, 1997; (d) Doyle, M. P.; Protopopova,
M. N. Tetrahedron 1998, 54, 7919.
product 2 as a red–brown crystal (81% yield). Mp
1
>300°C; 31P NMR l 31.50; H NMR (acetone-d6) l
2. (a) Aratani, T.; Yoneyoshi, Y.; Nagase, T. Tetrahedron
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Chem. Res. 1993, 26, 339.
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hedron Lett. 1990, 31, 6005; (b) Evans, D. A.; Woerpal,
K. A.; Hinman, M. M.; Faul, M. M. J. Am. Chem. Soc.
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Umbricht, G.; Weber, B.; Pfaltz, A. Helv. Chim. Acta
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7, 1603; (f) Bedekar, A. V.; Koroleva, E. B.; Anderson, P.
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8.22 (s, 2H), 7.53 (dd, J=2.8 Hz, 9.4 Hz, 2H), 7.33–
7.11 (m, 32H), 6.22 (d, J=9.4 Hz, 2H), 2.59–2.57 (m,
2H), 1.8–1.0 (m, 8H); 13C NMR: 173.1, 156.5, 134.6–
122.5 (m, C-Ph), 73.2, 28.6, 24.6. Anal. calcd for
C56H48N4O6P2Ru: C, 64.92; H, 4.67; N, 5.41; O, 9.27;
P, 5.98; Ru, 9.76. Found: C, 64.52; H, 5.02; N, 4.85%.
ESI MS: m/z 1037 [M+H]+.
4.3. General experimental using [Ru(p-cymene)Cl2]2 as
precursor
In a 25 mL Schlenk tube, [Ru(p-cymene)Cl2]2 (0.0061 g,
0.01 mmol) was mixed with the ligand 1 (0.021 mmol)
in iso-propanol (3 mL), then Et3N (0.0167 mL, 6
equiv.; or 0.0053 mL, 2 equiv.) was added. The solution
was refluxed for two hours, then concentrated in vacuo.
The residue was vacuum dried at 90°C for 30 min and
cooled to room temperature. The solid was dissolved in
CH2Cl2 (5 mL), and styrene (10 mmol) was added to
the solution. Ethyl diazoacetate (0.114 g, 1 mmol) in
CH2Cl2 (5 mL) was added through a syringe pump over
a period of six hours. The resulting mixture was stirred
for another eight hours. The catalyst-free sample was
analyzed as described in the footnote to Table 1.
6. (a) Ito, K.; Katsuki, T. Tetrahedron Lett. 1993, 34, 2661;
(b) Ito, K.; Yoshitake, M.; Katsuki, T. Heterocycles
1996, 42, 305.
7. (a) Doyle, M. P.; Brandes, B. D.; Kazala, A. P.; Pirters,
R. J.; Jarstfer, M. B.; Watkins, L. M.; Eagle, C. T. J.
Tetrahedron Lett. 1990, 31, 6613; (b) Davies, H. M. L.;
Bruzinski, P. R.; Lake, D. H.; Kong, N.; Fall, M. J. J.
Am. Chem. Soc. 1996, 118, 6897.
4.4. General experimental using Ru(PPh3)Cl2 as
precursor
8. Jacobsen, E. N. In Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; VCH: New York, 1993; Chapter 4, p. 159.
9. (a) Schaus, S. E.; Larrow, J. F.; Jacobsen, E. N. J. Org.
Chem. 1997, 62, 4197; (b) Hansen, K. B.; Leighton, J. L.;
Jacobsen, E. N. J. Am. Chem. Soc. 1996, 118, 10924.
10. Tokunaga, M.; Larrow, J. F.; Kakuichi, F.; Jacobsen, E.
N. Science 1997, 277, 936.
In a 25 mL Schlenk tube, Ru(PPh3)Cl2 (0.0191 g, 0.02
mmol) was mixed with the ligand 1 (0.021 mmol) in
iso-propanol, and then Et3N (0.0167 mL, 6 equiv.) was
added. The solution was refluxed for two hours, then
concentrated in vacuo. The residue was washed with
Et2O (3×1 mL) and vacuum dried at 90°C for 30 min
and cooled to room temperature. The solid was dis-
solved in CH2Cl2 (5 mL), and styrene (10 mmol) was
added to the solution. A solution of ethyl diazoacetate
(0.114 g, 1 mmol) in CH2Cl2 (5 mL) was added through
a syringe pump over a period of six hours. The result-
ing mixture was stirred for another eight hours. The
catalyst-free sample was analyzed as described in the
footnote to Table 1.
11. Schaus, S. E.; Branalt, J.; Jacobsen, E. N. J. Org. Chem.
1998, 63, 403.
12. Belokon, Y. N.; Caveda-Cepas, S.; Green, B.; Ikonnikov,
N. S.; Khrustalev, V. N.; Larichev, V. S.; Moscalenko,
M. A.; North, M.; Orizu, C.; Tararov, V. I.; Tasinazzo,
M.; Timofeeva, G. I.; Yashkina, L. V. J. Am. Chem. Soc.
1999, 121, 3968.
13. Some salen ligands have been reported for asymmetric
alkene aziridination and cyclopropanation using their
copper(II) complexes, but the system proved to be uni-
formly ineffective for these reactions. See: (a) Li, Z.;
Conser, K. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1993,
115, 5326; (b) Li, Z.; Quan, R. W.; Jacobsen, E. N. J.
Am. Chem. Soc. 1995, 117, 5889.
14. (a) Fukuda, T.; Katsuki, T. Synlett 1995, 825; (b)
Fukuda, T.; Katsuki, T. Tetrahedron 1997, 53, 7201.
15. (a) Yamada, T.; Ikeno, T.; Sekino, H.; Sato, M. Chem.
Lett. 1999, 719; (b) Ikeno, T.; Sato, M.; Yamada, T.
Chem. Lett. 1999, 1345.
Acknowledgements
This work was supported by the National Science
Foundation of China (29933050).
References
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ing substituents at C(3) and C(3%) could not catalyze the
reaction. However, in (NO)Ru–salen-catalyzed cyclo-
propanation, there are bulky chiral groups at C(3) and
C(3%). See Refs. 14 and 18.
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released during coordination would result in decreased
yield and enantioselectivity.
20. In Co(III)–salen-catalyzed asymmetric cyclopropanation
.
.