Synthesis of new chiral terpyridine mono-N-oxide and di-N-oxide ligands and their applications in copper-catalyzed asymmetric cyclopropanation

Article abstract of DOI:10.1016/S0957-4166(02)00270-7

New families of chiral terpyridine mono-N-oxides L₁-L₃ and di-N-oxides L₄-L₆, were synthesized in moderate to good yields by simple oxidation of their corresponding terpyridines with m-CPBA. The copper(II) trifl

Full text of DOI:10.1016/S0957-4166(02)00270-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1485–1492
Synthesis of new chiral terpyridine mono-N-oxide and
di-N-oxide ligands and their applications in copper-catalyzed
asymmetric cyclopropanation
Wing-Leung Wong, Wing-Sze Lee and Hoi-Lun Kwong*
Department of Biology and Chemistry and Open Laboratory of Chirotechnology of the Institute of Molecular Technology for
drugs Discovery and Synthesis, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China
Received 9 May 2002; accepted 5 June 2002
Abstract—New families of chiral terpyridine mono-N-oxides L –L and di-N-oxides L –L , were synthesized in moderate to good
1
3
4
6
yields by simple oxidation of their corresponding terpyridines with m-CPBA. The copper(II) triflate complexes of these ligands
were found to be highly effective catalysts for asymmetric cyclopropanation of styrene with ethyl diazoacetate. The isolated yields
of cyclopropane were excellent and the enantiomeric excesses of up to 83% were observed. Competition experiments with
+
substituted styrenes showed good | correlations with z=−0.70 for mono-N-oxide L and z=−0.69 for di-N-oxide L . © 2002
3
6
Elsevier Science Ltd. All rights reserved.
1
9
enantioselective Aldol additions to ketones and allyla-
tion of aldehydes, respectively.
1
. Introduction
20
1
Aromatic amine N-oxides are known to be good lig-
ands for transition metals and lanthanides
such, they have been used extensively in catalysis. Pyri-
dine N-oxides, for examples, have been used as termi-
nal oxidants for alkene epoxidation and
hydroxylation and served as additives for rate
enhancement in metal-catalyzed processes.
applications of chiral pyridine N-oxides in asymmetric
catalysis have also started to appear in the past few
years. Among the most salient examples, Nakajima and
co-workers reported the use of biquinoline N,N%-diox-
ides as catalytic ligands for asymmetric allylation of
2
–4
Polydentate ligands containing the N-oxide moiety
have been of great interest because of their coordina-
2,2%:6%,2¦-Terpyridine di-N-oxide 1
is one such multidentate ligand that can be prepared
from terpyridine. Recently, Nagata and co-workers
employed this ligand for the study of its coordination
and as
21–24
tion properties.
5
–7
25
8
9
–14
Useful
26
chemistry with transition metals.
1
5
16,17
aldehydes and conjugate additions of thiols;
Fu et
al. demonstrated the utilization of planar-chiral pyri-
18
dine N-oxides for desymmetrization of meso-epoxides
and Denmark’s and Ko cˇ ovsky’s groups independently
revealed the application of chiral bipyridine N-oxides in
In our previous studies, we have developed a new class
of chiral C -symmetric terpyridines, 2–4, for copper-
2
*
0
Corresponding author. Fax: (852)-2788-7406; e-mail: bhhoik@cityu.edu.hk
957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00270-7

1
486
W.-L. Wong et al. / Tetrahedron: Asymmetry 13 (2002) 1485–1492
2
7,28
catalyzed asymmetric cyclopropanation.
These lig-
N-oxides can be synthesized using m-chloroperbenzoic
acid (m-CPBA) as oxidizing agent. It was found that
the formation of mono- and di-N-oxides can be con-
trolled by using a suitable ratio of the oxidant and
terpyridine, with an optimum reaction time.
ands can also be converted to the corresponding N-
oxides by simple oxidation reaction. Herein, we
describe the preparation of new chiral terpyridine
mono- and di-N-oxide derivatives L –L from terpyridi-
1
6
nes 2–4. The use of these ligands in copper-catalyzed
asymmetric cyclopropanation of styrene with ethyl dia-
zoacetate was demonstrated.
In the first attempt, terpyridine mono-N-oxides L –L
1
3
were prepared by stirring terpyridines 2–4 with 1 equiv.
of m-CPBA at room temperature for
8 h in
dichloromethane. Surprisingly, less than 5% of the
desired product was obtained using this procedure. In
order to obtain better yields, the procedure was
modified by increasing the amount of m-CPBA (1.3–2
equiv.) and reacting for 2–8 h (Scheme 1). If the
reaction ran for over 8 h it led to serious oxidation of
2
. Results and discussion
Syntheses of pyridine mono- and di-N-oxides through
N-oxidation were reported previously by Thummel and
co-workers. With this simple procedure, terpyridine
2
5
Scheme 1.

W.-L. Wong et al. / Tetrahedron: Asymmetry 13 (2002) 1485–1492
1487
the mono-N-oxides to di-N-oxides. However, small
amounts of starting terpyridines and di-N-oxides were
still found in most of these reactions. After flash column
detailed study. Elemental analysis indicated that these
compounds are 1:1 ligand to copper complexes with two
chloride ions. These green coloured complexes can be
used directly as catalysts in cyclopropanation of styrene
with diazoacetate but no enantioselectivity was observed
with them.
chromatography, terpyridine N-oxides L –L3 were
1
obtained in moderate yields between 30 and 50%. Ter-
pyridine di-N-oxides L –L were prepared by stirring
4
6
terpyridines 2–4 with excess m-CPBA (4 equiv.) at room
temperature for 8 h in dichloromethane (Scheme 2). After
work-up and recrystallization from diethyl ether, high
purity products with isolated yields of 64–70% were
obtained.
In contrast, when the complexes were generated in situ
by stirring 2 mol% of Cu(OTf) and 2.2 mol% of L in
2
CH Cl and stirring with 4 equiv. of ethyl diazoacetate
2
2
for 30 minutes at 40°C, the catalysts induced some
enantioselectivity. The experimental results are summa-
rized in Table 1 and the results of 2–4 from our previous
1
The isolated N-oxides L –L were characterized by H
1
6
28
NMR analysis. Terpyridine mono- and di-N-oxides can
be easily distinguished by the symmetry of their H NMR
study are also included for comparison. The yields of
the isolated cyclopropane esters were excellent, ranging
from 82 to 90% for terpyridine mono-N-oxides (entries
1–3) to 90–97% (entries 4–6) for the terpyridine di-N-
oxides. Enantioselectivities of between 23 and 83% were
obtained.
1
spectra. By taking L and L as models for mono- and
3
6
di-N-oxides, respectively, the seven protons of the ter-
pyridine ring of L clearly show six sets of doublet signals
3
at l 7.00, 7.31, 8.07, 8.18, 8.49, 8.86 and one triplet at
l 7.91, while for L , the seven protons of the terpyridine
6
ring only show as three doublets at l 6.98, 7.84, 8.72 and
one triplet at l 7.92 because of the molecular symmetry.
Of the terpyridine N-oxides, mono-N-oxide L gave the
3
best result with 73% ee for trans-isomer and 83% ee for
cis-isomer (entry 3). The trans/cis ratio of the cyclo-
propanes was determined by GC analysis of the reaction
mixture. The isomer ratio was found between 66:34 to
76:24, favoring the trans-isomer over the cis-isomer. The
absolute configurations of cyclopropane esters formed
from styrene were found to be (1R,2R) for the trans-iso-
mer and (1R,2S) for the cis-isomer. With respect to the
absolute configuration of the products, the sense of
asymmetric induction by these ligands was the same as
those observed with the corresponding terpyridine lig-
1
27
Comparing the H NMR of terpyridines with the
corresponding di-N-oxides, we found that their patterns
are very similar and the only difference is the chemical
shift of some of the aromatic protons.
The copper(II) chloride complexes of terpyridine N-
oxides were prepared in good yields by reaction of the
appropriate N-oxides with CuCl . However, because of
2
difficulties in preparing some of these ligands in greater
amounts, copper complexes Cu(L )Cl and Cu(L )Cl
3
2
6
2
27,28
were the only two complexes that were chosen for
ands.
Scheme 2.

1
488
W.-L. Wong et al. / Tetrahedron: Asymmetry 13 (2002) 1485–1492
Table 1. Asymmetric cyclopropanation of styrene with copper(II)-terpyridine mono-N-oxide and di-N-oxide complexes
Entrya
Ligand L
Yield (%)b
trans/cis
% ee (config.)c
cis
trans
1
2
3
4
5
6
L1
L2
L3
L4
L5
L6
2
85
82
90
92
97
90
84
88
81
75:25
76:24
66:34
74:26
76:24
70:30
75:25
76:24
67:33
24 (1S,2S)
31 (1R,2R)
73 (1R,2R)
20 (1S,2S)
25 (1R,2R)
31 (1R,2R)
26 (1S,2S)
32 (1R,2R)
72 (1R,2R)
24 (1S,2R)
27 (1R,2S)
83 (1R,2S)
20 (1S,2R)
23 (1R,2S)
43 (1R,2S)
26 (1S,2R)
30 (1R,2S)
82 (1R,2S)
d
7
d
8
3
4
d
9
a
Diazoacetate (0.2 equiv.) was used for the reduction of the Cu(II) catalysts before the start of the cyclopropanation reaction.
Isolated yield after column chromatography.
b
c
Enantiomeric excesses were determined by HPLC using a Daicel Chiralcel OJ column, and the absolute configurations were determined by
2
9
comparing the order of elution with those of samples with known configuration.
d
Results obtained from Ref. 28.
If one compares ligands having the same chiral group,
the terpyridine mono-N-oxide or di-N-oxide from 4
gave the best results, while those from 2 gave the worst
results. Another interesting point to notice is that ter-
pyridine mono-N-oxides always give better enan-
tiomeric excess than that of their corresponding
terpyridine di-N-oxides. Besides, all terpyridine mono-
N-oxides gave similar diastereoselectivity and enan-
tioselectivity when compared to the corresponding
parent terpyridine ligands while terpyridine di-N-oxides
gave very different and inferior enantioselectivity.
In order to obtain more information about the nature
of the intermediates involved in the reaction, competi-
tion experiments using L3 and L6 as ligands in the
cyclopropanation of four substituted styrenes were car-
ried out. With ethyl diazoacetate (EDA), the rates of
cyclopropanation of the substituted styrenes relative to
that of styrene were measured by GC analysis. The plot
Figure 1. Hammett plot for the cyclopropanation of substi-
tuted styrenes with EDA using Cu(L
)(OTf) complex as
3
2
catalyst.
+
of log(k /k ) values versus Hammett constants | are
X
H
shown in Figs. 1 and 2 for the mono-N-oxide L and
3
the di-N-oxide L , respectively. As expected, in both
6
cases, electron-donating groups led to higher reaction
rate, while an electron-withdrawing group resulted in
+
lowered reaction rate. Good | correlations were
obtained with z=−0.70 for mono-N-oxide L and z=−
3
0
.69 for di-N-oxide L . The value for the chiral ter-
6
pyridine ligand 4 was found to be z=−0.76 under the
28
same reaction condition. These small negative values
of z indicated the formation of electrophilic metal–car-
bene complex intermediate and also a moderate positive
charge built-up at the benzylic carbon in the transition
state during the reaction. The different z values of L3
and 4, however, suggests that even though the enan-
tioselectivities of these two ligands are similar, the
Figure 2. Hammett plot for the cyclopropanation of substi-
tuted styrenes with EDA using Cu(L )(OTf)2 complex as
6
catalyst.

W.-L. Wong et al. / Tetrahedron: Asymmetry 13 (2002) 1485–1492
1489
active species are quite different during reaction. This
3. Conclusion
result also rules out the possibility that L ligand is
3
reduced to 4 during reaction.
In summary, new families of chiral terpyridine mono-
N-oxide and di-N-oxide ligands L –L were successfully
1
6
Further investigation is necessary to find out the active
species in these reactions. However, with the results
from absolute configuration, enantioselectivity and the
z values of the Hammett study, we would like to
propose that terpyridine mono-N-oxide and terpyridine
di-N-oxide are bidentate N,O-coordinating ligands in
this catalytic system, while the parent terpyridine,
instead of acting as a tridentate N,N,N-coordinating
synthesized by simple oxidation reactions. These lig-
ands are good for copper-catalyzed asymmetric cyclo-
propanation. Enantiomeric excess up to 83% and yield
up to 97% were achieved. Work is in progress to study
the mechanism of the reactions and extend the applica-
tion of these ligands in other catalytic asymmetric
reactions.
2
7,28
ligand,
is a bidentate N,N-coordinating ligand in
the active species for the cyclopropanation.
4. Experimental
4.1. General
In these proposed models, three coordinated copper
intermediates are involved, with ligands providing two
of the coordinating atoms and the carbene providing
the third atom (Scheme 3). The rectangular plane
shown in Scheme 3 contains a copper, a carbene carbon
and the two substituents of the carbene. The alkenes
approach to the top face, (but not the bottom face), of
the plane to provide the correct absolute configuration
of the products. This model of approach is in agree-
ment with the one previously cited by Pflatz for other
Chemicals were of reagent-grade quality were obtained
commercially. Terpyridines 2–4 were prepared accord-
2
7,28
ing to the literature.
IR spectra (KBr plates) in the
−
1
range 500–4000 cm were recorded on a Perkin–Elmer
1
13
model 1600 FTIR spectrometer. H and C NMR
spectra were recorded on a Varian 300 MHz Mercury
instrument. Elemental analyses were performed on a
Vario EL elemental analyzer. ESMS were recorded
using a PE SCIEX API 365 mass spectrometer. Optical
rotations were measured using a JASCO DIP-370 digi-
tal polarimeter. Melting points were measured using an
electrothermal digital melting point apparatus.
2
9
N,N-bidentate ligands.
These models explain the absolute configurations and
the similar enantioselectivities obtained with L and 4
3
as the different coordinations between L and 4 do not
3
lead to a great change in the steric environment where
the carbene moves (backward away from the rectangu-
lar plane) during carbene transfer. This is in sharp
4.2. Chiral terpyridine mono-N-oxide L1
To a solution of chiral terpyridine 2 (0.21 g, 0.5 mmol)
in dry CH Cl (3 mL), a solution of m-chloroperben-
contrast to the reactions of L as the non-coordinated
6
2
2
N-oxide may force the entire pyridine group to move
away from the metal carbene thus giving a sterically
very different environment. Besides, as both N-oxide
and di-N-oxide are N,O-coordinating in the model, it
also explains nicely why L and L gave very similar z
zoic acid (0.31 g, 1 mmol) in dry CH Cl (3 mL) was
2 2
added slowly. The resulting solution was then stirred
for 2 h. The reaction was quenched with saturated
NaHCO3 solution and diluted with dichloromethane
(10 mL). The resulting solution was washed with satu-
rated NaHCO3 solution (2×20 mL), and then with
water (20 mL). The organic layer was then collected
and dried over anhydrous magnesium sulfate. After
removal of solvent, the crude product was purified by
3
6
values (−0.7 versus −0.69) in the Hammett competition
study when compared to each other but different z
values when compared to 4 (−0.76), which is N,N-coor-
dinating in the model.
Scheme 3. Proposed models in copper-catalyzed cyclopropanation using L , L and 4.
3
6

1
490
W.-L. Wong et al. / Tetrahedron: Asymmetry 13 (2002) 1485–1492
flash chromatography, eluting with diethyl ether and
quenched with saturated NaHCO3 solution and
diluted with dichloromethane (10 mL). The resulting
followed by Et O:methanol (25:1), to obtain chiral
2
terpyridine mono-N-oxide L (0.066 g, 30% yield).
solution was washed with saturated NaHCO solution
1
3
2
5
1
Mp=194.8–196.2°C; [h] =−29.6 (c 0.45, CHCl ); H
(2×20 mL) and then with water (20 mL). The organic
layer was then collected and dried over anhydrous
magnesium sulfate. After removal of solvent, the
crude product was purified by flash chromatography
with diethyl ether–petroleum ether (1:1), to obtain
D
3
NMR (300 MHz, CDCl ): l 0.72 (s, 3H), 0.78 (s,
3
3H), 1.33 (d, 2H, J=5.1 Hz), 1.46 (s, 3H), 1.49 (s,
3H), 2.33–2.38 (m, 2H), 2.73–2.83 (m, 2H), 3.00 (d,
2H, J=2.4 Hz), 3.04 (d, 2H, J=2.4 Hz), 3.12 (t, 1H,
J=5.4 Hz), 4.16 (t, 1H, J=5.4 Hz), 7.20 (d, 1H,
J=7.8 Hz), 7.55 (d, 1H, J=7.5 Hz), 7.89 (t, 1H,
J=7.5 Hz), 8.11 (d, 1H, J=7.8 Hz), 8.26 (d, 1H,
J=7.8 Hz), 8.41 (d, 1H, J=7.8 Hz), 8.87 (d, 1H,
chiral terpyridine mono-N-oxide L (0.116 g, 50%
3
25
yield). Mp=164.6–168.3°C; [h] =−17.8 (c 0.5,
D
1
CHCl ); H NMR (300 MHz, CDCl ): l 0.68 (s, 6H),
3
3
1.34 (d, 2H, J=9.9 Hz), 1.43 (s, 6H), 1.48 (d, 3H,
J=7.2 Hz), 1.54 (d, 3H, J=6.6 Hz), 2.16–2.22 (m,
2H), 2.53–2.61 (m, 2H), 2.79–2.84 (m, 2H), 3.26–3.29
(m, 1H), 3.44–3.51 (m, 1H), 7.00 (d, 1H, J=7.8 Hz),
7.31 (d, 1H, J=8.1 Hz), 7.91 (t, 1H, J=8.1 Hz), 8.07
(d, 1H, J=8.1 Hz), 8.18 (d, 1H, J=7.5 Hz), 8.49 (d,
1
3
J=7.8 Hz); C NMR (300 MHz, CDCl ): l 21.3,
3
2
3
1
1
1.4, 25.8, 26.1, 30.3, 30.4, 30.9, 31.3, 31.6, 39.1, 39.2,
9.9, 40.2, 40.3, 118.8, 120.9, 124.7, 125.0, 125.4,
30.6, 133.2, 135.9, 136.8, 145.1, 149.8, 152.0, 156.0,
−
1
56.3, 165.8; IR (KBr): 2922, 1558, 1429 cm . Anal
1
3
calcd for C H N O·(CH CH ) O: C, 77.46; H, 8.08;
1H, J=7.8 Hz), 8.86 (d, 1H, J=8.1 Hz); C NMR
2
9
31
3
3
2 2
N, 8.21. Found: C, 77.11; H, 7.85; N, 8.03%. Positive
ion MS (API) m/z: 438 (M +H).
(300 MHz, CDCl ): l 14.9, 18.3, 20.6, 21.0, 26.0,
26.4, 28.3, 28.6, 35.0, 38.9, 41.5, 41.6, 46.9, 47.1, 47.3,
3
+
4
7.6, 117.8, 120.7, 123.1, 124.8, 125.1, 133.5, 136.9,
4.3. Chiral terpyridine mono-N-oxide L2
142.3, 145.2, 146.1, 149.7, 150.3, 156.0, 160.2; IR
−
1
(
KBr): 2910, 1568, 1437 cm . Anal calcd for
To a solution of chiral terpyridine 3 (0.225 g, 0.5
mmol) in dry CH Cl (3 mL), a solution of m-
C H N O·(CH CH ) O: C, 77.88; H, 8.40; N, 7.78.
31
35
3
3
2 2
Found: C, 77.46; H, 8.03; N, 7.75%. Positive ion MS
2
2
+
chloroperbenzoic acid (0.236 g, 0.75 mmol) in dry
CH Cl (3 mL) was added slowly. The resulting solu-
(API) m/z: 466 (M +H).
2
2
tion was then stirred for 8 h. The reaction was
quenched with saturated NaHCO3 solution and
diluted with dichloromethane (10 mL). The resulting
4
.5. General procedure for the preparation of chiral
terpyridine di-N-oxide ligands
solution was washed with saturated NaHCO solution
3
To a stirred solution of m-chloroperbenzoic acid (4.0
mmol) in dichloromethane (6 mL), the chiral ter-
pyridine ligand (1.0 mmol) was added. The yellow
solution was then stirred under nitrogen atmosphere
at room temperature for 8 h. The reaction was
quenched with saturated NaHCO3 solution and
diluted with dichloromethane (50 mL). The resulting
(
2×20 mL), and then with water (20 mL). The
organic layer was then collected and dried over anhy-
drous magnesium sulfate. After removal of solvent,
the crude product was purified by flash chromatogra-
phy, eluting with petroleum ether–ethyl acetate (10:1)
and followed by dichloromethane–ethyl acetate (4:1),
to obtain chiral terpyridine mono-N-oxide L (0.093
2
solution was washed with saturated NaHCO solution
2
5
D
3
g, 40% yield). Mp=193.5–197.8°C; [h] =−50.4 (c
.5, CHCl ); H NMR (300 MHz, CDCl ): l 0.60 (s,
(
2×50 mL) and then with water (50 mL). The organic
1
3 3
0
layer was then collected and dried over anhydrous
magnesium sulfate. After removal of solvent, the
crude chiral terpyridine di-N-oxide product was
purified by recrystallizing from diethyl ether.
3
H), 0.79 (s, 3H), 0.98 (s, 3H), 1.02 (s, 3H), 1.12–1.34
(
2
(
1
m, 4H), 1.40 (s, 3H), 1.72 (s, 3H), 1.86–1.97 (m,
H), 2.11–2.22 (m, 2H), 2.89 (d, 1H, J=4.2 Hz), 2.91
d, 1H, J=4.2 Hz), 7.19 (d, 1H, J=7.8 Hz), 7.47 (d,
H, J=7.8 Hz), 7.89 (t, 1H, J=7.8 Hz), 8.07 (d, 1H,
J=7.2 Hz), 8.18 (d, 1H, J=7.5 Hz), 8.48 (d, 1H,
4.5.1. Chiral terpyridine di-N-oxide L . The general
4
13
J=7.8 Hz), 8.80 (d, 1H, J=7.8 Hz); C NMR (300
procedure described above was followed, using chiral
terpyridine 2 (0.421 g, 1 mmol) and m-chloroperben-
zoic acid (1.26 g, 4.0 mmol) to afford pure chiral
MHz, CDCl ): l 10.3, 12.8, 18.8, 19.3, 20.1, 20.4,
3
2
1
1
6.1, 26.3, 31.2, 31.8, 51.6, 52.0, 54.2, 55.7, 56.7, 57.2,
18.3, 119.7, 120.7, 124.8, 125.8, 128.5, 136.8, 141.7,
46.0, 146.4, 149.6, 152.3, 154.7, 156.4, 169.9; IR
terpyridine di-N-oxide L . (0.317 g, 70% yield). Mp=
4
2
5
1
227.6–229.4°C; [h] =−1089.9 (c 0.5, CHCl );
NMR (300 MHz, CDCl ): l 0.78 (s, 6H), 1.31 (d,
H
D
3
−
1
(
KBr): 2960, 1557, 434 cm . Anal calcd for
3
C H N O·CH OH: C, 77.22; H, 7.89; N, 8.44.
2H, J=9.9 Hz), 1.49 (s, 6H), 2.33–2.37 (m, 2H),
2.75–2.83 (m, 2H), 3.03 (d, 4H, J=2.4 Hz), 4.15 (t,
2H, J=5.7 Hz), 7.17 (d, 2H, J=8.4 Hz), 7.89 (d, 2H,
J=8.1 Hz), 7.90 (t, 1H, J=8.1 Hz), 8.77 (d, 2H,
31
35
3
3
Found: C, 77.72; H, 7.73; N, 8.35%. Positive ion MS
+
(
API) m/z: 466 (M +H).
13
4.4. Chiral terpyridine mono-N-oxide L3
J=8.1 Hz); C NMR (300 MHz, CDCl ): l 21.4,
3
2
5.8, 30.3, 31.6, 39.1, 39.8, 40.3, 124.6, 125.5, 125.6,
To a solution of chiral terpyridine 4 (0.225 g, 0.5
mmol) in dry CH Cl (3 mL), a solution of m-
133.3, 135.8, 144.8, 150.3, 156.3; IR (KBr): 2908,
−
1
1558,
1439
cm .
Anal
calcd
for
2
2
chloroperbenzoic acid (0.205 g, 0.65 mmol) in dry
CH Cl (3 mL) was added slowly. The resulting solu-
C H N O ·(CH CH ) O: C, 75.11; H, 7.83; N, 7.96.
29
31
3
2
3
2 2
Found: C, 74.48; H, 7.51; N, 7.60%. Positive ion MS
2
2
+
tion was then stirred for 8 h. The reaction was
(API) m/z: 454 (M +H).

W.-L. Wong et al. / Tetrahedron: Asymmetry 13 (2002) 1485–1492
1491
4
.5.2. Chiral terpyridine di-N-oxide L . The general
4.7. General procedure for competition reactions for
copper catalysts
5
procedure described above was followed, using chiral
terpyridine 3 (0.449 g, 1 mmol) and m-chloroperbenzoic
acid (1.26 g, 4.0 mmol) to afford pure chiral terpyridine
To a two-necked round-bottomed flask were added
di-N-oxide L (0.308 g, 64% yield). Mp=254.6–
Cu(OTf) (0.0036 g, 0.01 mmol), CH Cl (1 mL) and
5
2
2
2
2
5
1
2
57.4°C; [h] =−214.2 (c 0.5, CHCl ); H NMR (300
terpyridine mono-N-oxide L or di-N-oxide L (0.011
D
3
3 6
MHz, CDCl ): l 0.78 (s, 6H), 0.98 (s, 6H), 1.14–1.36
mmol) under nitrogen. The solution was stirred at
room temperature for 2 h. Styrene (1 mmol) and substi-
tuted styrene (1 mmol) were added to the stirred solu-
tion. Ethyl diazoacetate (0.5 mmol) in CH Cl (0.5 mL)
3
(
2
m, 4H), 1.70 (s, 6H), 1.88–1.97 (m, 2H), 2.11–2.21 (m,
H), 2.90 (d, 2H, J=3.3 Hz), 7.13 (d, 2H, J=7.5 Hz),
.77 (d, 2H, J=7.5 Hz), 7.85 (t, 1H, J=8.1 Hz), 8.62
7
2
2
13
(d, 2H, J=8.1 Hz); C NMR (300 MHz, CDCl ): l
was added to the reaction mixture in one portion. The
mixture was allowed to stir at room temperature for 16
h. The ratios of resulting cyclopropanes were deter-
mined by GC.
3
1
1
1
7
8
2.9, 18.9, 20.5, 26.4, 31.4, 52.2, 55.9, 57.5, 119.9, 125.7,
26.0, 135.6, 146.4, 146.6, 150.6, 154.8; IR (KBr): 2950,
−
1
557, 1434 cm . Anal calcd for C H N O ·H O: C,
3
1
35
3
2
2
4.52; H, 7.46; N, 8.41. Found: C, 75.34; H, 7.24; N,
+
.77%. Positive ion MS (API) m/z: 482 (M +H).
4.8. General procedure for preparation of copper(II)
terpyridine di-N-oxide complexes [Cu(L)Cl2]
4
.5.3. Chiral terpyridine di-N-oxide L . The general
6
Terpyridine N-oxide L (0.2 mmol) in dichloromethane
procedure described above was followed, using chiral
terpyridine 4 (0.421 g, 1 mmol) and m-chloroperbenzoic
acid (1.26 g, 4.0 mmol) to afford pure chiral terpyridine
(
2 mL) was added to a solution of CuCl ·2H O (0.034
2 2
g, 0.2 mmol) in ethanol (5 mL). The solution was
heated under reflux overnight to ensure complete com-
plexation. The solution was then cooled and diethyl
ether was added until precipitate was formed. The
product was isolated by filtration and washed with
diethyl ether. The complexes were characterized by IR,
UV, CHN and MS analyses.
di-N-oxide L (0.312 g, 65% yield). Mp=155.3–
6
2
D 3
5
1
1
58.9°C; [h] =−74.7 (c 0.3, CHCl ); H NMR (300
MHz, CDCl ): l 0.69 (s, 6H), 1.44 (s, 6H), 1.47 (d, 2H,
3
J=6.6 Hz), 1.54 (d, 6H, J=6.6 Hz), 2.19–2.24 (m, 2H),
2
2
7
.55–2.63 (m, 2H), 2.83 (t, 2H, J=5.7 Hz), 3.45 (m,
H), 6.98 (d, 2H, J=7.8 Hz), 7.84 (d, 2H, J=8.1 Hz),
13
.92 (t, 1H, J=8.1 Hz), 8.72 (d, 2H, J=7.8 Hz);
C
Cu(L )Cl . The above procedure was followed using L
3
3
2
NMR (300 MHz, CDCl ): l 14.9, 20.7, 25.9, 28.3, 35.0,
3
to give Cu(L )Cl2 (0.11 g, 95%). IR (KBr): 2924.6,
3
4
1
1.7, 47.1, 47.6, 123.4, 125.1, 125.6, 135.9, 137.4, 145.4,
46.1, 150.4; IR (KBr): 2932, 1564, 1440 cm . Anal
−
1
1
593.2, 1470.3 cm . Visible spectrum (CH Cl ), u
−1
2 2 max
(
m): 262 (33000), 335 (22000), 472 (254), 866 nm (163).
calcd for C H N O ·(CH OH): C, 74.82; H, 7.65; N,
3
1
35
3
2
3
Anal. calcd for C H Cl CuN O·4H O: C, 55.39; H,
31
35
2
3
2
8
.18. Found: C, 74.31; H, 7.33; N, 8.33%. Positive ion
6
.45; N, 6.25. Found: C, 56.19; H, 6.24; N, 6.05%.
+
+
MS (API) m/z: 482 (M +H).
Positive ion MS (API) m/z: 563 (M −Cl).
4
.6. General procedure for copper-catalyzed
Cu(L )Cl . The above procedure was followed using L
6
6
2
cyclopropanation
to give Cu(L )Cl2 (0.11 g, 90%). IR (KBr): 2929.7,
6
1
588.1, 1449.8. Visible spectrum (CH Cl ), u
(m): 259
2
2
max
To a two-necked round-bottomed flask were added
(35000), 317 (20000), 384 (3000), 471 (320), 884 nm
Cu(OTf) (0.0072 g, 0.02 mmol), CH Cl (2 mL) and
(210). Anal. calcd for C H Cl CuN O ·4H O: C,
2
2
2
31 35
2
3
2
2
the chiral terpyridine N-oxide ligand L (0.022 mmol)
under nitrogen. The solution was stirred at room tem-
perature for 2 h. Styrene (0.417 g, 4 mmol) and fol-
lowed with ethyl diazoacetate (0.2 mmol) were added
and the mixture was heated with stirring at 40°C for 0.5
h. After cooling to room temperature, a solution of
ethyl diazoacetate (1 mmol) in CH Cl (0.5 mL) was
54.10; H, 6.30; N, 6.11. Found: C, 53.36; H, 6.04; N,
6.01%. Positive ion MS (API) m/z: 579 (M −Cl).
+
Acknowledgements
2
2
added to the reaction mixture over a period of 4 h using
a syringe pump. After the addition of ethyl diazoac-
etate, the mixture was allowed to stir for 16 h at room
temperature. The solvent was removed and the crude
product obtained was purified by column chromatogra-
phy (hexane/EtOAc). All the cyclopropanes obtained
This research was substantially supported by the Hong
Kong Research Grants Council CERG grant (CityU
1096/98P) and the Area of Excellence Scheme estab-
lished under the University Grants Committee of the
Hong Kong Special Administrative Region, China
(Project No. AoE/P-10/01).
1
are known compounds and were characterized by H
1
3
and C NMR, IR, and GC–MS. The enantiomeric
excesses of the cyclopropanes were determined by
HPLC using a Daicel Chiralcel OJ column. The abso-
lute configurations were determined by comparing with
the order of elution of samples with known configura-
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