Self-assembly approach toward chiral bimetallic catalysts: Bis-urea-functionalized (Salen)cobalt complexes for the hydrolytic kinetic resolution of epoxides

Article abstract of DOI:10.1002/chem.201002600

A series of novel bis-urea-functionalized (salen)Co complexes has been developed. The complexes were designed to form self-assembled structures in solution through intermolecular urea-urea hydrogen-bonding interactions. These bis-urea (salen)Co catalysts resulted in rate acceleration (up to 13atimes) in the hydrolytic kinetic resolution (HKR) of rac-epichlorohydrin in THF by facilitating cooperative activation, compared to the monomeric catalyst. In addition, one of the bis-urea (salen)Co^III catalyst efficiently resolves various terminal epoxides even under solvent-free conditions by requiring much shorter reaction time at low catalyst loading (0.03-0.05amol %). A series of kinetic/mechanistic studies demonstrated that the self-association of two (salen)Co units through urea-urea hydrogen bonds was responsible for the observed rate acceleration. The self-assembly study with the bis-urea (salen)Co by FTIR spectroscopy and with the corresponding (salen)Ni complex by ¹HaNMR spectroscopy showed that intermolecular hydrogen-bonding interactions exist between the bis-urea scaffolds in THF. This result demonstrates that self-assembly approach by using non-covalent interactions can be an alternative and useful strategy toward the efficient HKR catalysis.

Full text of DOI:10.1002/chem.201002600

DOI: 10.1002/chem.201002600
Self-Assembly Approach toward Chiral Bimetallic Catalysts:
Bis-Urea-Functionalized (Salen)Cobalt Complexes for the Hydrolytic
Kinetic Resolution of Epoxides**
Jongwoo Park, Kai Lang, Khalil A. Abboud, and Sukwon Hong*[a]
Abstract: A series of novel bis-urea-
functionalized (salen)Co complexes has
been developed. The complexes were
designed to form self-assembled struc-
tures in solution through intermolecu-
lar urea–urea hydrogen-bonding inter-
actions. These bis-urea (salen)Co cata-
lysts resulted in rate acceleration (up
to 13 times) in the hydrolytic kinetic
resolution (HKR) of rac-epichlorohy-
drin in THF by facilitating cooperative
activation, compared to the monomeric
catalyst. In addition, one of the bis-
urea (salen)CoIII catalyst efficiently re-
solves various terminal epoxides even
under solvent-free conditions by requir-
ing much shorter reaction time at low
catalyst loading (0.03–0.05 mol%). A
series of kinetic/mechanistic studies
demonstrated that the self-association
of two (salen)Co units through urea–
urea hydrogen bonds was responsible
for the observed rate acceleration. The
self-assembly study with the bis-urea
(salen)Co by FTIR spectroscopy and
with the corresponding (salen)Ni com-
1
plex by H NMR spectroscopy showed
that intermolecular hydrogen-bonding
interactions exist between the bis-urea
scaffolds in THF. This result demon-
strates that self-assembly approach by
using non-covalent interactions can be
an alternative and useful strategy
toward the efficient HKR catalysis.
Keywords: bis-urea
effects epoxide opening
hydrogen bonds · self-assembly
· cooperative
·
·
Introduction
a covalent linker; these multinuclear complexes been de-
vised to enforce a cooperative pathway. Thus, dimeric,[5] oli-
gomeric,[6] dendritic,[7] polymeric,[8] colloidal,[9] and encapsu-
lated[10] (salen)Co complexes showed much improved cata-
lytic efficiency in the HKR, whereas requiring lower catalyst
loading.
Cooperative activation is a general phenomenon in bio-
chemical transformations and many biological catalysts such
as enzymes have evolved to achieve high efficiency and se-
lectivity through dual activation.[1] There have been growing
efforts to develop efficient asymmetric catalysts based on
the concept of cooperative activation.[2] One of the conven-
tional approaches particularly toward bi- or multimetallic
catalyst design involves tethering metal centers through co-
valent bonds or metal coordination in order to place metal
centers in close proximity.[3] For example, a second-order de-
pendence on the chiral (salen)Co (salen=bis-(salicyliden)-
ethylendiaminato) catalyst in the hydrolytic kinetic resolution
(HKR) of epoxides[4] led to the development of a number of
multinuclear (salen)Co structures connected mainly through
It would be possible to replace the covalent bond tether
with non-covalent bonding interaction such as hydrogen
bonds. This self-assembly approach is a highly attractive
strategy because various combinations of homo- and hetero-
bimetallic systems can be generated in solution by mixing
self-assembling monomeric units, without synthesizing indi-
vidual bimetallic species. Recently, hydrogen-bonding inter-
actions have drawn much attention in asymmetric catalysis.
This relatively weak hydrogen bond plays a crucial role in a
number of organocatalytic reactions for the activation and
orientation of substrates.[11] Hydrogen-bonding interactions
have also been recognized as a structural element to con-
struct supramolecular catalysts[12] such as encapsulated cata-
lysts,[13] artificial metalloenzymes,[14] bidentate ligands,[15] or-
ganocatalysts,[16] and dinuclear catalysts.[17]
[a] J. Park, K. Lang, Dr. K. A. Abboud, Prof. Dr. S. Hong
Department of Chemistry, University of Florida
Gainesville, FL 32611-7200 (USA)
Fax : (+1)352-846-0296
We previously reported a novel self-assembly-based ap-
proach toward the dinuclear (salen)Co catalyst through ami-
nopyridine/2-pyridone hydrogen-bonding interactions; these
catalyst resulted in significant rate acceleration in the enan-
E-mail: sukwon@ufl.edu
[**] Salen=bis-(salicyliden)ethylendiaminato.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002600.
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FULL PAPER
tioselective Henry reactions.[18] It raised an intriguing ques-
tion whether the self-assembly approach can be applicable
to other bimetallic transformations, such as HKR of termi-
nal epoxides. Very recently, Wꢁrnmark and co-workers de-
veloped novel supramolecular (salen)Cr catalysts featuring
2-pyridone-containing isoquinolinone and quinolinone hy-
drogen-bonding pairs to achieve higher reaction rates for
meso-epoxide opening reactions with TMSN3 (TMS=trime-
thylsilyl), however, the enantioselectivity observed was gen-
erally lower than 10% ee (ee=enantiomeric excess).[17c] Our
initial attempt in HKR with our aminopyridine/2-pyridone-
based self-assembled dinuclear catalyst was unsuccessful,[19]
prompting us to search for other readily installable hydro-
gen-bonding pairs that can be systematically varied to mod-
ulate self-assembly strength and metal–metal distances. We
envisioned that the bis-urea motif could be utilized as a hy-
drogen-bonding unit in self-assembled (salen)Co catalysts
for HKR of epoxides (Scheme 1). Because N,N’-disubstitut-
Scheme 2. Self-assembly capable bis-urea (salen)cobalt complexes.
Bis-urea-functionalized (salen)CoII precatalysts (1a–k)
were synthesized in four steps from 5-(azidomethyl)-3-tert-
butyl-2-hydroxybenzaldehyde (3) (Scheme 3).[28] The alkyl-
and aryl-functionalized urea salicylaldehydes (4a–h and 4k)
were conveniently prepared by
the reaction of azide 3 with the
corresponding
isocyanates
under catalytic hydrogenation
conditions.[29] For the urea com-
pounds bearing reducible func-
tional groups under catalytic
hydrogenation conditions (4-Br-
C6H4- and 4-CN-C6H4-), an al-
ternative route was taken to
avoid potential reduction of
such substituents. Thus, salicy-
Scheme 1. Self-association of bis-urea (salen)cobalt complexes (OTs=tosylate).
ed ureas can provide directional hydrogen-bonding interac-
tions between two NH protons and the carbonyl group,[20]
the urea motif has been widely applied to the construction
of supramolecular architectures such as columns,[21] capsu-
les,[22] nanotubes,[23] channels,[24] supramolecular polymers,[25]
and organogels.[26] Furthermore, some bis- and tetra-urea
structures have shown self-assembly in polar media such as
THF or even in aqueous solution through the combination
of hydrogen-bonding and hydrophobic interactions.[22c,27]
Herein, we report new bis-urea-functionalized (salen)cobalt
catalysts and their improved catalytic efficiency in HKR of
epoxides at low catalyst loading (0.03–0.05 mol%).
Results and Discussion
Catalysts preparation: In the current ligand design, the CH2
spacer was employed to connect the N,N’-disubstituted urea
motif to the (salen)cobalt core (Scheme 2). In order to study
the influence of different end groups on the urea motif, vari-
ous alkyl- and aryl-substituted bis-urea (salen)Co complexes
were prepared. Prior to the catalytic reactions, the CoII pre-
catalysts 1a–k were oxidized to the active CoIII species 1a–
k·OTs by using 1.1 equivalent of p-TsOH (p-Ts=p-toluene-
sulfonyl) in the open air.
Scheme 3. Synthesis of the bis-urea (salen)CoII precatalysts.
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2237

S. Hong et al.
laldehydes 4i and 4j were obtained in good overall yields,
by the reaction of the acetal-protected amine 5[30] the with
corresponding isocyanates, followed by the removal of the
acetal protecting group. Then, the resulting urea-functional-
ized salicylaldehydes 4a–k were condensed with (R,R)-1,2-
diaminocyclohexane to afford the bis-urea salen ligands 6a–
k. Finally, the bis-urea (salen)CoII complexes 1a–k were ob-
under solvent-free conditions, which are environment-
friendly and cost-effective.[31] Because epoxide substrates
and diol products are generally liquid, it is possible to per-
form HKR under solvent-free or highly concentrated condi-
tions.[4,31] In addition, it would be necessary to avoid the use
of solvent particularly for volatile epoxides due to their iso-
lation by vacuum transfer. Therefore, solvent-free conditions
for HKR are highly desirable. To examine the catalytic ac-
tivity under highly-concentrated and solvent-free conditions,
kinetic resolution of rac-epichlorohydrin (5.0 mmol) was
performed at 238C with 0.7 equivalents of H2O and
0.05 mol% of 1k·OTs in THF (0.1 mL) and under solvent-
free conditions. It is important to note that bis-urea catalyst
1k·OTs exhibited significantly better performance than the
monomeric catalyst 2·OTs under both conditions (Figure 1).
tained by the reaction of CoACHTNUGRTNEUNG(OAc)2·4H2O with the corre-
sponding salen ligands in EtOH or iPrOH under argon at-
mosphere. All bis-urea (salen)CoII complexes were charac-
terized by high-resolution mass spectrometry and elemental
analysis.
Hydrolytic kinetic resolution: The new bis-urea-functional-
ized (salen)Co catalysts were evaluated by comparing reac-
tion rates for HKR of rac-epichlorohydrin (7a) in THF at
238C with 0.55 equivalents of H2O (Table 1). Tosylate was
Table 1. Kinetic data for the HKR of rac-epichlorohydrin catalyzed by
(salen)Co·OTs catalysts.[a]
[b,c]
Entry
Catalyst
R
kobs [hꢀ1
]
Relative rate[d]
1
2
3
4
5
6
7
8
1a·OTs
1b·OTs
1c·OTs
1d·OTs
1e·OTs
1 f·OTs
1g·OTs
1h·OTs
1i·OTs
1j·OTs
1k·OTs
2·OTs
Bn[e]
n-C6H13
n-C18H37
C6H5
4-CH3O-C6H4
3,5-(CF3)2C6H3
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
4-CN-C6H4
4-CF3-C6H4
–
3.2ꢂ10ꢀ1
3.5ꢂ10ꢀ1
5.4ꢂ10ꢀ1
6.5ꢂ10ꢀ1
6.5ꢂ10ꢀ1
7.4ꢂ10ꢀ1
6.7ꢂ10ꢀ1
1.00
4.2
4.6
7.2
8.6
8.6
9.7
8.8
13
9.5
6.7
13.7
1.0
9
7.2ꢂ10ꢀ1
5.1ꢂ10ꢀ1
1.04
10
11
12
7.6ꢂ10ꢀ2
[a] Reactions were carried out on a 5.0 mmol scale in THF (1.0 mL) at
([epoxide]/[epoxide]0)
238C. [b] kobs was determined from plots of ꢀln
N
ACHTUNGTRENNUNG
Figure 1. a) HKR of rac-epichlorohydrin (5.0 mmol) with 0.05 mol%
&
1k·OTs (^) and 2·OTs ( ) in THF (0.1 mL). b) HKR of rac-epichlorohy-
drin (5.0 mmol) under solvent-free conditions with 0.05 mol% 1k·OTs
&
^
(
) and 2·OTs ( ).
chosen as a counterion for this study and bromobenzene
was added as an internal standard. We were pleased to find
that all bis-urea (salen)Co·OTs catalysts showed significant
rate acceleration (4.2—13 times) compared to the monomer-
ic catalyst 2·OTs (Table 1, entries 1–11 versus entry 12). The
N-aryl end groups (Table 1, entries 4–11) show greater rate
acceleration than the N-alkyl end groups (Table 1, entries 1–
3). Electron-withdrawing groups on the phenyl ring
(Table 1, entries 6–11) appear to be better; however, the
substituent effect does not linearly correlate with the Ham-
mett parameter s. The 4-Cl-C6H4- and 4-CF3-C6H4- end
groups prove to be the best from the survey (Table 1, en-
tries 8 and 11), and the 4-CF3-C6H4- group (1k·OTs) was se-
lected for the further studies.
After 8 h, 92% ee (THF) and 93% ee (solvent-free) were
achieved with 0.05 mol% 1k·OTs, whereas only 35% ee
(THF) and 47% ee (solvent-free) were achieved with
0.05 mol% 2·OTs. Note that the self-assembled catalyst that
is potentially sensitive to the medium polarity, maintains its
catalytic efficiency under solvent-free conditions, although
the reaction medium continuously changes as the reaction
progresses.[31]
The substrate scope was then studied for solvent-free
HKR of epoxides by using 0.03–0.05 mol% bis-urea (sale-
n)Co catalyst 1k·OTs (Table 2). After the reaction was com-
pleted, the remaining epoxide was isolated by vacuum trans-
fer. To our delight, bis-urea (salen)Co catalyst 1k·OTs dis-
played improved performance for all four terminal epoxides
One of the impressive features of HKR catalyzed by
(salen)Co complexes is that this reaction can be carried out
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Self-Assembled Chiral Bimetallic Catalysts
FULL PAPER
Table 2. HKR of terminal epoxides under solvent-free conditions.[a]
the second-order-like kinetic dependence on the total cata-
lyst concentration, [cat]tot [Eq. (4)], is expected from self-as-
sembled systems with moderate K2 values under diluted
conditions [Eq. (5)], whereas the first-order kinetic depend-
ence is expected from covalently-tethered dimeric catalysts.
It is also interesting to note that the kinetics of the current
self-assembly conditions show correlation between the ob-
served rate constant (kobs) and the dimerization constant K2
[Eq. (5)].
Entry
R
Catalyst
[mol%]
Time
[h]
ee[b]
[%]
Yield[d]
[%]
N
1
2
3
4
5
6
7
8
CH2Cl (7a)
CH2Cl (7a)
1k·OTs (0.05)
2·OTs (0.05)
1k·OTs (0.05)
2·OTs (0.05)
1k·OTs (0.03)
2·OTs (0.03)
1k·OTs (0.03)
2·OTs (0.03)
14
71
8
32
8
24
14
42
99
96
99
98
99
99
99
99
41
42
43
43
43
43
41
42
CH2O
CH2O
ACHTUNGTRENNUNG
A
2
CH2CH3 (7c)
CH2CH3 (7c)
ACHTUNGTRENNUNG
ð1Þ
ð2Þ
ð3Þ
ð4Þ
K2 ¼ ½dimerꢁ=½monomerꢁ
rate / k ½dimerꢁ
ACHTUNGTRENNUNG
[a] Reactions were carried out with 0.7 equiv of H2O on 10–20 mmol
scales under solvent-free conditions at 238C. [b] ee values of the epoxide.
Determined by chiral GC-MS (Chiraldex g-TA). [c] Yields of isolated ep-
oxides based on rac-epoxides (50% theoretical maximum).
2
rate / kK2 ½monomerꢁ
½catꢁtot ¼ 2½dimerꢁþ½monomerꢁ
if ½dimerꢁ ꢂ ½catꢁtot
rate / kK2 f½catꢁtotꢀ2 ½dimerꢁg ꢃ kK2 ½catꢁtot
:
ð5Þ
2
2
examined (Table 2, entries 1, 3, 5, 7 versus entries 2, 4, 6, 8).
Compared to the monomeric catalyst 2·OTs, the bis-urea
(salen)Co catalyst 1k·OTs required much shorter reaction
time (8–14 vs. 24–71 h, respectively) to resolve epoxides
completely (99% ee) in good yields (41–43%) at low cata-
lyst loadings (0.03–0.05 mol%).
Second, control experiments were performed to deter-
mine whether the accessible NH groups are crucial for rate
acceleration. Two compounds lacking accessible urea NH
groups because of bulky ortho-isopropyl groups on the aryl
ꢀ
substituent (1l·OTs) or N Me substitution (9·OTs), were
Kinetic and mechanistic study: We hypothesized that the
rate enhancement can be attributed to the self-association
of (salen)Co units through urea–urea hydrogen bonding. A
series of kinetic/mechanistic studies was performed mainly
in THF to validate the main hypothesis. It is generally as-
sumed that the same mechanisms are operating under sol-
vent-free conditions.[4,31] First, kinetic studies showed that
the rate laws were second order in the cobalt concentration
for the bis-urea (salen)Co complex 1 f·OTs (Figure 2, rate /
tested for the HKR of rac-epichlorohydrin under the same
reaction conditions as described in Table 1. Both catalysts
resulted in slower reaction rate (relative rate=0.8 and 0.7
for 1l·OTs and 9·OTs, respectively), indicating that accessi-
ble urea NH groups are responsible for the observed rate
acceleration.
Figure 2. Kinetic analysis of the reaction order of the catalyst concentra-
tion (R2 =0.9906).
Third, additional control experiments were conducted to
rule out an alternative scenario involving electrophilic acti-
vation of epoxides by the urea functionality through double
hydrogen bonding.[32] Thus, two different N,N’-disubstituted
urea compounds (10 and 11) were added to the reaction
mixture in the presence of the monomeric catalyst 2·OTs
(Table 3). Both urea additives decreased the reaction rate in
the HKR of rac-epichlorohydrin. The electron-richer diben-
kobsACHTUNGTRENNUNG
[(salen)Co]2). This result indicates that the same bimetal-
lic mechanism is operating with the bis-urea (salen)Co com-
plex as with the monomeric (salen)Co complex 2·OTs.[4]
Assuming the dimeric aggregate is an actual catalytic spe-
cies, the rate law can be expressed in terms of the mono-
mer–dimer equilibrium constant K2 [Eqs. (1)–(3)]. Note that
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2239

S. Hong et al.
Table 3. Kinetic data for the HKR of rac-epichlorohydrin catalyzed by
2·OTs catalysts and urea additive.[a]
[b,c]
kobs [hꢀ1
]
Relative rate[d]
Figure 3. The NH stretching region of the FTIR spectra of 1k in THF at
three different concentration (1 (black), 2 (dark gray), and 3 mm (light
gray)) at 258C.
Entry
Additive ([mol%])
1
2
3
4
none
7.6ꢂ10ꢀ2
3.8ꢂ10ꢀ2
6.7ꢂ10ꢀ2
3.2ꢂ10ꢀ2
1.0
0.5
0.9
0.4
10 (0.1)
11 (0.1)
11 (0.4)
[a] Reactions were carried out on a 5.0 mmol scale in THF (1.0 mL) at
([epoxide]/[epoxide]0)
versus time. [c] Determined by chiral GC-MS (Chiraldex g-TA) relative
to an internal standard (C6H5Br). [d] Relative rate per 2·OTs.
ering the known bimetallic mechanism for the HKR of ep-
oxides, it is also possible that urea and bis-urea molecules
can exist as higher aggregates. With the equal K model
(K2 =Kn =K),[35] Ka values of 12 and 13 were determined to
be (70ꢄ29) and (32ꢄ0)mꢀ1, respectively.[34] Thus, both
models indicate that urea (salen)Ni complexes self-assemble
in THF with moderate association strength. However, fur-
ther study will be necessary to elucidate precise dimeriza-
tion/oligomerization behavior in this system. The mono-urea
(salen)Co complex 14·OTs was also prepared and tested for
the HKR of rac-epichlorohydrin under the same reaction
conditions as described in Table 1 to compare relative rates
(Figure 4b). It is interesting to note that the observed self-
association strengths of the bis- and mono-urea (salen)Ni
complexes (56 vs. 32mꢀ1) are in accordance with the ob-
served rate enhancements from the corresponding (sale-
n)CoIII catalysts (13 vs. 8.4).
238C. [b] kobs was determined from plots of ꢀln
G
ACHTUNGTRENNUNG
zyl urea 10 (Table 3, entry 2) and increased amounts of urea
additive (Table 3, entry 3 versus entry 4) resulted in slower
reaction rates. These results suggest that the urea additive
might function as
a competitive inhibitor, presumably
through coordination to the metal center. It also explains
why electron-deficient R groups showed better reactivity in
HKR (Table 1).
Self-association study: More direct experimental evidence
was sought for self-association through urea–urea hydrogen
bonding in solution. IR spectroscopy has been widely ap-
plied for studying self-assembly of urea and bis-urea com-
pounds because free NH groups and hydrogen-bonded NH
groups have different frequencies. FTIR experiments with
bis-urea (salen)Co 1k in THF (3 mm) at 258C revealed
strong hydrogen-bonded NH stretching vibrations (n˜ =3347
and 3295 cmꢀ1) in comparison to free NH stretching vibra-
tions (n˜ =3571 and 3505 cmꢀ1). The intensity of hydrogen-
bonded NH stretching vibrations was decreased with lower-
ing concentration, but the vibrations were still significant at
a 1 mm concentration (Figure 3). This result indicates that
the urea NH functionalities of the bis-urea (salen)Co com-
plexes are involved in intermolecular hydrogen-bonding
events in THF.
X-ray packing structure and MM2 calculation: The X-ray
structure of the bis-urea (salen)Ni complex 15 (R=Bn), ob-
tained by slow evaporation in DMF, revealed urea–urea hy-
drogen bonding between the salen units in the solid state.[36]
The crystal packing shows the interstack arrangement be-
tween two extensive hydrogen-bond networking layers (Fig-
ure 5a), however, the desired head-to-tail bimetallic ar-
rangement is not observed within the hydrogen-bonding net-
work (Figure 5b). Thus, MM2 calculations were carried out
to probe feasibility of such dimeric structures capable of
dual activation.[37] Optimizations were performed on a sim-
plified bis-urea (salen)Ni complex (R=Me) by using the
CAChe program (Fujitsu), and the two resulting plausible
energy-minimized structures are shown in Figure 5c.[38] Two
(salen)Ni units can be assembled through two urea–urea hy-
drogen-bonding interactions either in a parallel (P) or an
antiparallel (A) mode and the estimated Ni–Ni distances are
approximately 6 ꢃ in both modes.[39]
To evaluate the self-association strength, 1H NMR dilu-
tion experiments were performed by using the correspond-
ing bis- and mono-urea (salen)Ni complexes 12 and 13[33] at
258C in [D8]THF. Two NH proton signals of the urea group
in the Ni complexes were monitored upon variation of con-
centration (0.76–19.1 mm), and the downfield shifts of two
urea protons (Ddꢃ0.2 ppm) were observed with increasing
concentration. The dimerization constants of 12 and 13 were
estimated to be (56ꢄ22) and (32ꢄ3)mꢀ1, respectively, by
using the simple monomer–dimer model (Figure 4a and
b).[34] Although the monomer–dimer model was used consid-
Asymmetric hydrolysis of cyclohexene oxide: The improved
catalytic efficiency of the bis-urea (salen)Co catalyst can be
demonstrated in asymmetric hydrolysis of cyclohexene
oxide, which is known to be very challenging with monomer-
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Chem. Eur. J. 2011, 17, 2236 – 2245

Self-Assembled Chiral Bimetallic Catalysts
FULL PAPER
1
Figure 4. a) Concentration-dependent H NMR shift of two urea protons (Ha: aromatic, Hb: aliphatic) of 12 and dimerization constant of (salen)Ni com-
plexe 12 in [D8]THF at 258C. The data were fitted to the monomer–dimer model (solid line). Relative rates for HKR of rac-epichlorohydin catalyzed by
1
the corresponding (salen)Co complex 1l·OTs in THF. b) Concentration-dependent H NMR shift of two urea protons (Ha: aromatic, Hb: aliphatic) of 13
and dimerization constant of (salen)Ni complexe 13 in [D8]THF at 258C. The data were fitted to the monomer–dimer model (solid line). Relative rates
for HKR of rac-epichlorohydin catalyzed by the corresponding (salen)Co complex 14·OTs in THF.
Figure 5. a) X-ray packing structures of 15 showing interstack arrangement between two hydrogen-bond networking layers. b) Observed hydrogen-
bonded network in the packing structure of 15. c) Two plausible structures of the bis-urea (salen)Ni dimer: antiparallel (A) and parallel (P) mode.
d) Structure of 15.
ic (salen)Co catalyst (Scheme 4). After 45 h, 1k·OTs gave
the desired diol product with much higher yield (62%) and
enantiomeric excess (75%) than the monomeric catalyst
2·OTs (9% yield and 45% ee).[40]
Scheme 4. Asymmetric hydrolysis of cyclohexene oxide (16) (TBME=
methyl tert-butyl ether).
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S. Hong et al.
3.38 (m, 2H), 1.93–1.83 (m, 2H), 1.83–1.74 (m, 2H), 1.69–1.56 (m, 2H),
1.49–1.38 (m, 2H), 1.31 ppm (s, 18H); 13C NMR (75 MHz, [D6]DMSO):
d=165.9, 158.7, 155.0, 140.4, 136.2, 129.1, 128.7, 128.5, 121.0, 117.8, 117.6,
71.0, 42.4, 34.3, 32.5, 29.1, 23.8 ppm; HRMS (APCI-TOF): m/z calcd for
C44H55N6O4: 731.4279 [M+H]+; found: 731.4291.
6e: 67% yield, yellow solid; 1H NMR (300 MHz, CDCl3): d=13.63 (s,
2H), 7.95 (s, 2H), 7.62 (s, 2H), 7.05–7.00 (m, 6H), 6.66 (d, J=9.1 Hz,
4H), 6.12 (s, 2H), 6.03 (s, 2H), 3.73–3.63 (m, 4H), 3.70 (s, 6H), 3.31–3.28
(m, 2H), 2.18–2.14 (m, 2H), 2.00–1.97 (m, 2H), 1.84–1.81 (m, 2H), 1.63–
1.55 (m, 2H), 1.18 ppm (s, 18H); 13C NMR (75 MHz, CDCl3): d=166.4,
159.0, 157.5, 155.5, 137.1, 131.9, 128.2, 127.7, 122.2, 117.6, 114.0, 73.0,
55.3, 43.0, 34.5, 32.7, 29.1, 24.6 ppm; HRMS (APCI-TOF): m/z calcd for
C46H59N6O6: 791.4491 [M+H]+; found: 791.4493.
6 f: 86% yield, yellow solid; 1H NMR (500 MHz, [D6]DMSO): d=14.09
(s, 2H), 9.22 (s, 2H), 8.46 (s, 2H), 8.07 (s, 4H), 7.51 (s, 2H), 7.17 (d, J=
2.0 Hz, 2H), 7.06 (d, J=1.7 Hz, 2H), 6.87 (t, J=5.9 Hz, 2H), 4.15 (d, J=
6.2 Hz, 4H), 3.45–3.38 (m, 2H), 1.93–1.83 (m, 2H), 1.83–1.74 (m, 2H),
1.69–1.56 (m, 2H), 1.49–1.38 (m, 2H), 1.25 ppm (s, 18H); 13C NMR
(125 MHz, [D6]DMSO): d=165.8, 158.8, 154.6, 142.6, 136.2, 130.5 (q, J=
32 Hz), 128.9, 128.6, 128.4, 123.4 (q, J=271 Hz), 117.7, 117.1, 113.4, 71.1,
42.4, 34.2, 32.5, 29.0, 23.8 ppm; HRMS (APCI-TOF): m/z calcd for
C48H51F12N6O4: 1003.3775 [M+H]+; found: 1003.3801.
6g: 52% yield, yellow solid; 1H NMR (300 MHz, [D6]DMSO): d=14.09
(s, 2H), 8.48–8.45 (m, 4H), 7.39–7.35 (m, 4H), 7.18 (s, 2H), 7.07–7.01 (m,
4H), 6.41 (s, 2H), 4.13 (s, 4H), 3.43 (m, 2H), 1.93–1.83 (m, 2H), 1.83–
1.74 (m, 2H), 1.69–1.56 (m, 2H), 1.49–1.38 (m, 2H), 1.30 ppm (s, 18H);
13C NMR (75 MHz, [D6]DMSO): d=165.9, 158.8, 156.8 (d, J=237 Hz),
155.1, 136.8 (d, J=2.6 Hz), 136.2, 129.1, 128.7, 128.6, 119.2 (d, J=7.4 Hz),
117.8, 115.0 (d, J=22 Hz), 71.0, 42.4, 34.3, 32.5, 29.1, 23.8 ppm; HRMS
(ESI-TOF): m/z calcd for C44H53F2N6O4: 767.4091 [M+H]+; found:
767.4087.
Conclusion
In conclusion, we have developed novel bis-urea-functional-
ized (salen)Co catalysts that are designed to self-assemble
through urea–urea hydrogen bonding. An optimized bis-
urea (salen)CoIII catalyst shows improved reaction rate (up
to 13 times) in HKR of epoxides. Kinetic/mechanistic study
results are consistent with the idea that self-assembly
through urea–urea hydrogen bonding is responsible for the
observed rate enhancement. This work demonstrates that
hydrogen bonding can be utilized to construct chiral bimet-
allic HKR catalysts. Modifications of ligand structures to
further improve the catalytic efficiency are currently in
progress.
Experimental Section
General: THF, CH2Cl2, and Et2O were passed through two packed col-
umns of neutral alumina under positive pressure prior to use. All the
chemicals used were commercially available and were used as received
without further purification. NMR spectra were recorded by using Varian
FT-NMR machines, operating at 300 and 500 MHz for 1H NMR and at
75.4 and 125 MHz for 13C NMR. Fourier transform infrared (FTIR) spec-
tra were recorded with a Perkin–Elmer Spectrum One FTIR Spectrome-
ter in CaF2 cells of 1 mm path length. High-resolution mass spectra were
recorded on a MALDI-TOF spectrometer, an APCI-TOF spectrometer,
or an ESI-TOF spectrometer. Enantiomeric excesses were determined by
chiral GC-MS analysis by using a Chiraldex g-TA column.
6h: 85% yield, yellow solid; 1H NMR (300 MHz, CDCl3): d=13.69 (s,
2H), 7.95 (s, 4H), 7.06–6.94 (m, 10H), 6.28 (s, 2H), 6.04 (s, 2H), 3.71–
3.64 (m, 4H), 3.31–3.28 (m, 2H), 2.17–2.13 (m, 2H), 2.00–1.97 (m, 2H),
1.84–1.81 (m, 2H), 1.63–1.55 (m, 2H), 1.15 ppm (s, 18H); 13C NMR
(75 MHz, CDCl3): d=166.1, 159.2, 157.0, 137.4, 128.8, 128.1, 127.8, 127.4,
127.0, 121.3, 121.0, 117.7, 73.0, 43.0, 34.6, 32.7, 29.0, 24.5 ppm; HRMS
(APCI-TOF): m/z calcd for C44H53Cl2N6O4: 799.3500 [M+H]+; found:
799.3531.
General procedure for the preparation of bis-urea salen ligands 6a–l: Sal-
icylaldehyde (0.36 mmol, 2.0 equiv) was added to a solution of (1R,2R)-
cyclohexane-1,2-diamine (0.18 mmol) in THF (5 mL) at room tempera-
ture, and then allowed to stir for 3–20 h. The solution was concentrated
under reduced pressure and the residue was purified by column chroma-
tography on silica-gel (n-hexane/EtOAc 5:1 then 2:1 or 1:2) to give the
resulting bis-urea salen as a yellow solid.
6a: 99% yield, yellow solid; 1H NMR (300 MHz, [D6]DMSO): d=14.02
(s, 2H), 8.42 (s, 2H), 7.29–7.14 (m, 12H), 6.98 (s, 2H), 6.33–6.25 (m, 4H),
4.18 (d, J=6.0 Hz, 4H), 4.05 (d, J=5.4 Hz, 4H), 3.45–3.38 (m, 2H), 1.93–
1.83 (m, 2H), 1.83–1.74 (m, 2H), 1.69–1.56 (m, 2H), 1.49–1.38 (m, 2H),
1.31 ppm (s, 18H); 13C NMR (75 MHz, [D6]DMSO): d=166.5, 159.2,
158.6, 141.6, 136.8, 130.4, 129.1, 129.0, 128.8, 127.6, 127.2, 118.4, 71.7,
43.6, 43.3, 35.0, 33.2, 29.8, 24.5 ppm; HRMS (APCI-TOF): m/z calcd for
C46H59N6O4: 759.4592 [M+H]+; found: 759.4620.
6b: 94% yield, yellow solid; 1H NMR (300 MHz, CDCl3): d=13.57 (s,
2H), 7.94 (s, 2H), 6.97 (d, J=2.0 Hz, 2H), 6.03 (s, 2H), 5.90 (s, 2H), 5.74
(s, 2H), 3.74–3.53 (m, 4H), 3.28–3.25 (m, 2H), 3.04 (q, J=6.3 Hz, 4H),
2.17–2.11 (m, 2H), 1.97–1.94 (m, 2H), 1.81–1.72 (m, 2H), 1.55–1.46 (m,
2H), 1.44–1.37 (m, 4H), 1.28–1.23 (m, 12H), 1.21 (s, 18H), 0.85 ppm (t,
J=6.8 Hz, 6H); 13C NMR (75 MHz, CDCl3): d=166.4, 159.4, 158.9,
137.0, 128.3, 128.2, 128.0, 117.6, 72.8, 43.2, 40.3, 34.6, 32.7, 31.6, 30.3, 29.5,
29.1, 26.7, 22.6, 14.0 ppm; HRMS (ESI-TOF): m/z calcd for C44H71N6O4:
747.5531 [M+H]+; found: 747.5526.
6c: 92% yield, yellow solid; 1H NMR (300 MHz, CDCl3): d=13.71 (s,
2H), 8.01 (s, 2H), 7.07 (s, 2H), 6.34 (s, 2H), 5.21 (s, 2H), 5.13 (s, 2H),
3.97–3.74 (m, 4H), 3.28–3.25 (m, 2H), 3.11 (td, J=6.5, 6.5 Hz, 4H), 2.13–
1.79 (m, 6H), 1.54–1.38 (m, 6H), 1.31 (s, 18H), 1.26 (s, 60H), 0.88 ppm
(t, J=6.8 Hz, 6H); 13C NMR (75 MHz, CDCl3): d=166.3, 159.2, 158.7,
137.2, 128.4, 128.1, 117.8, 72.5, 43.8, 40.5, 34.7, 32.7, 32.0, 30.4, 29.7, 29.5,
29.4, 29.3, 27.0, 24.4, 22.7, 14.1 ppm; HRMS (ESI-TOF): m/z calcd for
C68H119N6O4: 1083.9287 [M+H]+; found: 1083.9223.
6i: 91% yield, yellow solid; 1H NMR (300 MHz, [D6]DMSO): d=14.09
(s, 2H), 8.57 (s, 2H), 8.48 (s, 2H), 7.44–7.36 (m, 8H), 7.17 (d, J=2.0 Hz,
2H), 7.06 (d, J=2.0 Hz, 2H), 6.50 (t, J=5.8 Hz, 2H), 4.12 (d, J=5.8 Hz,
4H), 3.46 (m, 2H), 1.92–1.88 (m, 2H), 1.88–1.80 (m, 2H), 1.76–1.60 (m,
2H), 1.54–1.44 (m, 2H), 1.30 ppm (s, 18H); 13C NMR (75 MHz,
[D6]DMSO): d=165.9, 158.9, 155.0, 139.9, 136.4, 131.6, 131.4, 129.1,
128.7, 119.7, 117.9, 112.5, 71.1, 42.5, 34.4, 32.6, 29.2, 23.9 ppm; HRMS
(ESI-TOF): m/z calcd for C44H53Br2N6O4: 887.2490 [M+H]+; found:
887.2469.
6j: 55% yield, yellow solid; 1H NMR (300 MHz, [D6]DMSO): d=14.10
(s, 2H), 8.99 (s, 2H), 8.47 (s, 2H), 7.67–7.64 (m, 4H), 7.57–7.54 (m, 4H),
7.18 (d, J=2.0 Hz, 2H), 7.07 (d, J=2.0 Hz, 2H), 6.69 (t, J=5.8 Hz, 2H),
4.14 (d, J=5.7 Hz, 4H), 3.46 (m, 2H), 1.94–1.90 (m, 2H), 1.88–1.80 (m,
2H), 1.76–1.60 (m, 2H), 1.54–1.44 (m, 2H), 1.29 ppm (s, 18H); 13C NMR
(75 MHz, [D6]DMSO): d=165.9, 158.9, 154.5, 144.9, 136.3, 133.1, 128.8,
128.7, 119.4, 117.8, 117.4, 102.4, 71.0, 42.4, 34.3, 32.5, 29.1, 23.8 ppm;
HRMS (ESI-TOF): m/z calcd for C46H53N8O4: 781.4184 [M+H]+; found:
781.4170.
6k: 89% yield, yellow solid; 1H NMR (300 MHz, [D6]DMSO): d=14.10
(s, 2H), 8.87 (s, 2H), 8.48 (s, 2H), 7.60–7.53 (m, 8H), 7.18 (d, J=2.0 Hz,
2H), 7.08 (d, J=2.0 Hz, 2H), 6.62 (t, J=5.7 Hz, 2H), 4.15 (d, J=5.7 Hz,
4H), 3.44 (m, 2H), 1.93–1.83 (m, 2H), 1.83–1.74 (m, 2H), 1.69–1.56 (m,
2H), 1.49–1.38 (m, 2H), 1.29 ppm (s, 18H); 13C NMR (75 MHz,
[D6]DMSO): d=165.9, 158.8, 154.7, 144.2, 136.3, 128.9, 128.7, 128.6,
125.9, 124.6 (q, J=270 Hz), 121.0 (q, J=32 Hz), 117.8, 117.2, 71.0, 42.4,
34.3, 32.5, 29.0, 23.8 ppm; HRMS (ESI-TOF): m/z calcd for
C46H53F6N6O4: 867.4027 [M+H]+; found: 867.4024.
6d: 81% yield, yellow solid; 1H NMR (300 MHz, [D6]DMSO): d=14.09
(s, 2H), 8.48 (s, 2H), 8.39 (s, 2H), 7.36–7.16 (m, 10H), 7.07 (s, 2H), 6.88
(t, J=7.2 Hz, 2H), 6.43 (t, J=5.7 Hz, 2H), 4.12 (d, J=5.7 Hz, 4H), 3.45–
2242
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 2236 – 2245

Self-Assembled Chiral Bimetallic Catalysts
FULL PAPER
6l: 92% yield, yellow solid; 1H NMR (300 MHz, [D6]DMSO): d=14.02
(s, 2H), 8.43 (s, 2H), 7.37 (s, 2H), 7.23 (s, 2H), 7.17 (d, J=7.9 Hz, 2H),
7.08 (m, 4H), 7.03 (s, 2H), 6.46 (s, 2H), 4.11 (s, 4H), 3.46 (m, 2H), 3.10
(m, 2H), 1.94–1.90 (m, 2H), 1.88–1.80 (m, 2H), 1.76–1.60 (m, 2H), 1.54–
1.44 (m, 2H), 1.34 (s, 18H), 1.07 ppm (d, J=6.8 Hz, 24H); 13C NMR
(75 MHz, [D6]DMSO): d=165.7, 158.6, 156.9, 146.7, 136.1, 133.0, 129.9,
128.3, 126.8, 122.7, 117.6, 71.0, 42.5, 34.3, 32.6, 29.1, 27.8, 23.8, 23.6 ppm;
HRMS (ESI-TOF): m/z calcd for C56H79N6O4: 899.6157 [M+H]+; found:
899.6165.
p-toluenesulfonic acid monohydrate in THF (0.01m, 0.55 mL, 1.1 equiv
per catalyst) was added and the solution was stirred in air for 30 min.
After removing the solvent by rotary evaporation, racemic epichlorohy-
drin (426 mg, 5.0 mmol), bromobenzene (50 mL, internal standard), and
THF (1.0 mL) were added to the oxidized (salen)Co complex. The vial
was placed into a water bath at 238C and H2O (50 mL, 0.55 equiv) was
added in one portion. The reaction progress was monitored by the re-
moval of aliquots from the reaction mixture, filtration through silica gel
with diethyl ether as eluent, and chiral GC-MS analysis (Chiraldex g-TA,
708C, isothermal, tRACHTNUGTRENNUG(major)=4.24, tRACHTUNTGREN(NUGN minor)=4.68 min). The slopes of
General procedure for the preparation of (salen)cobalt complexes 1a–l:
Co
(OAc)2·4H2O (0.21 mmol, 1.0 equiv) was added to a solution or sus-
the least square lines for the plots of ꢀln
ACHTUGTNREN(UNG [epoxide]/CAHTUNGTRENN[UGN epoxide]0) versus
pension of the appropriate salen ligand (0.21 mmol) in EtOH (5 mL),
and heated at reflux for 3 h under argon. The precipitate was collected
by filtration, washed with EtOH, and then dried under vacuum for 24 h
to give the (salen)cobalt complex.
time were determined.
General procedure for hydrolytic kinetic resolution of epoxides under
solvent-free conditions: A vial equipped with a stir bar was charged with
1k (4.6 mg, 5 mmol, 0.05 mol%). A solution of p-toluenesulfonic acid
monohydrate in THF (0.01m, 1.1 mL, 1.1 equiv per catalyst) was added
and the solution was stirred in air for 30 min. After removing the solvent
by rotary evaporation, racemic epichlorohydrin (925 mg, 10 mmol) was
added. The vial was placed into a water bath at 238C and H2O (126 mL,
0.70 equiv) was added in one portion. The reaction mixture became ho-
mogeneous within 30 min. After the reaction was stirred at 238C for
14 h, the remaining epoxide was isolated by vacuum transfer (RT,
0.5 Torr) into a receiving flask precooled at ꢀ788C. The recovered epox-
ide was dried over anhydrous MgSO4 and filtered to give (S)-epichloro-
hydrin 7a (390 mg, 42%) as a colorless liquid. The ee value of the recov-
ered epichlorohydrin was determined to be 99% by chiral GC-MS analy-
1a: 68% yield, red solid; HRMS (ESI-TOF): m/z calcd for
C46H56CoN6O4: 815.3690 [M]+; found: 815.3678; elemental analysis calcd
(%) for C46H56CoN6O4: C 55.73, H 5.46, N 8.12; found C 55.73, H 5.46, N
8.12.
1b: 39% yield, red solid; HRMS (ESI-TOF): m/z calcd for
C44H68CoN6O4: 803.4629 [M]+; found: 803.4629; elemental analysis calcd
(%) for C44H68CoN6O4: C 65.73, H 8.53, N 10.45; found C 65.40, H 8.86,
N 10.26.
1c: 56% yield, reddish brown solid; HRMS (MALDI-TOF): m/z calcd
for C68H116CoN6O4: 1139.8385 [M]+; found: 1139.8399; elemental analysis
calcd (%) for C68H116CoN6O4: C 71.60, H 10.25, N 7.37; found C 71.61, H
10.56, N 7.19.
sis (Chiraldex g-TA, 708C, isothermal,
tRACTHNGUTRE(NNUG major)=4.24, tRACHTUNGTRENNUNG(minor)=
4.68 min). Absolute configuration of the major isomer was determined to
1d: 60% yield, red solid; HRMS (ESI-TOF): m/z calcd for
C44H52CoN6O4: 787.3377 [M]+; found: 787.3343; elemental analysis calcd
(%) for C44H52CoN6O4: C 67.08, H 6.65, N 10.67; found C 66.79, H 6.88,
N 10.48.
be (S) by comparison of the retention time with literature data.[4c]
X-ray crystallography: Suitable crystals of 15 were selected and data
were collected at 100 K on a Bruker DUO system equipped with an
APEX II area detector and a graphite monochromator utilizing MoKa ra-
diation (l=0.71073 ꢃ). Cell parameters were refined by using up to 9999
reflections. A hemisphere of data was collected by using the w-scan
method (0.58 frame width). Absorption corrections by integration were
applied based on measured indexed crystal faces. The structure was
solved by the direct methods in SHELXTL6,[41] and refined by using full-
matrix least squares. The non-hydrogen atoms were treated anisotropical-
ly, whereas the hydrogen atoms were calculated in ideal positions and
were riding on their respective carbon atoms. There are two disordered
regions in the complex. The hexyl ring C1–C6 was refined in two parts
with the site occupation factors dependently refined. Similarly, the
phenyl ring on C40 is also disordered and was also refined in two parts
with the site occupation factors similarly refined. All amino protons were
obtained from a difference Fourier map and refined freely. A total of 502
parameters were refined in the final cycle of refinement by using 4506 re-
flections with I>2s(I) to yield R1 and wR2 of 6.92 and 14.56%, respec-
tively. Refinement was done by using F2. Refinement details for 15:
C46H56N6NiO4; Mr =815.68; T=100(2) K; wavelength=0.71073 ꢃ; crystal
1e: 67% yield, reddish brown solid; HRMS (ESI-TOF): m/z calcd for
C46H56CoN6O6; 847.3588 [M]+; found: 847.3569; elemental analysis calcd
(%) for C46H56CoN6O6: C 65.16, H 6.66, N 9.91; found C 65.39, H 6.92, N
9.81.
1 f: 55% yield, reddish brown solid; HRMS (ESI-TOF): m/z calcd for
C48H48CoF12N6O4; 1059.2872 [M]+; found: 1059.2975; elemental analysis
calcd (%) for C48H48CoF12N6O4: C 54.40, H 4.56, N 7.93; found C 54.18,
H 4.53, N 7.58.
1g: 79% yield, orange-red solid; HRMS (ESI-TOF): m/z calcd for
C44H50CoF2N6O4; 823.3188 [M]+; found: 823.3181; elemental analysis
calcd (%) for C44H50CoF2N6O4: C 64.15, H 6.12, N 10.20; found C 64.39,
H 6.54, N 9.95.
1h: 61% yield, reddish brown solid; HRMS (ESI-TOF): m/z calcd for
C44H50Cl2CoN6O4; 855.2592 [M]+; found: 855.2546; elemental analysis
calcd (%) for C44H50Cl2CoN6O4: C 61.68, H 5.88, N 9.81; found C 61.28,
H 5.98, N 9.59.
1i: 75% yield, reddish brown solid; HRMS (ESI-TOF): m/z calcd for
C44H50Br2CoN6O4: 945.1572 [M]+; found: 945.1591; elemental analysis
calcd (%) for C44H50Br2CoN6O4: C 55.88, H 5.33, N 8.89; found C 55.95,
H 5.46, N 8.63.
¯
system: triclinic; space group P1; a=8.6817(11), b=15.721(2), c=
15.803(2); a=76.708(3), b=86.868(3), g=78.889(3); V=2059.6(5) ꢃ3;
Z=2; 1calcd =1.315 Mgm·3; m=0.523 mmꢀ1; F
ACTHNUTRGNE(UNG 000)=868; crystal size=
0.20ꢂ0.08ꢂ0.04 mm3; q range=1.35–25.008; index ranges: ꢀ10ꢅhꢅ10,
ꢀ18ꢅkꢅ14, ꢀ18ꢅlꢅ18; reflections collected 20352, independent re-
1j: 32% yield, reddish brown solid; HRMS (ESI-TOF): m/z calcd for
C46H50CoN8O4: 837.3287 [M]+; found: 837.3290; elemental analysis calcd
(%) for C46H50CoN8O4: C 65.94, H 6.01, N 13.37; found C 65.56, H 6.06,
N 13.03.
flections 7262 [RACTHUNTGRNEUNG(int)=0.0729], completeness to q=25.008, 100.0%; ab-
sorption correction: none; max./min. transmission 0.9819/0.9031; data/re-
straints/parameters 7262/0/502; goodness-of-fit on F2 1.116; final R indi-
ces [I>2s(I)]; R1 =0.0692, wR2 =0.1456 [4506]; R indices (all data): R1 =
1k: 37% yield, reddish brown solid (note: replacement of ethanol with
isopropanol in the general procedure afforded 1k in higher yield
(77%)); HRMS (ESI-TOF): m/z calcd for C46H50CoF6N6O4; 923.3124
[M]+; found: 923.3140; elemental analysis calcd (%) for
C46H50CoF6N6O4: C 59.80, H 5.46, N 9.10; found C 59.57, H 5.46, N 8.87.
0.1136, wR2 =0.1542; largest diff. peak/hole 0.373/ꢀ0.414 eꢃꢀ3
.
Molecular mechanics calculations: Molecular mechanics calculations
were performed by using augmented MM2 force field parameters, as im-
plemented in CAChe version 6.1.1.[37] Calculations were performed by
using a simplified bis-urea (salen)nickel complex. The atomic coordinates
in the (salen)Ni fragment were obtained from the crystal structure data
of 15. The (salen)Ni fragment was locked during computation. Steepest
descent search was used to locate the energy minimum. Optimization
1l: 56% yield, red solid; HRMS (ESI-TOF): m/z calcd for
C56H76CoN6O4: 955.5255 [M]+; found: 955.5250; elemental analysis calcd
(%) for C56H76CoN6O: C 70.34, H 8.01, N 8.79; found C 70.46, H 8.37, N
8.72.
Reaction rates determination: A vial equipped with a stir bar was
charged with (salen)cobalt catalyst (2.5 mmol, 0.05 mol%). A solution of
continued until the energy change was less than 0.001 kcalmolꢀ1
.
Chem. Eur. J. 2011, 17, 2236 – 2245
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2243

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Acknowledgements
This work was supported by the U.S. National Science Foundation
(CHE-0957643). The authors wish to thank Dr. Sangbae Lee for help
with MM2 calculation and Michael Rodig for discussion.
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Chem. Eur. J. 2011, 17, 2236 – 2245

Self-Assembled Chiral Bimetallic Catalysts
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Received: September 9, 2010
Published online: January 10, 2011
Chem. Eur. J. 2011, 17, 2236 – 2245
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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