Heterobimetallic dual-catalyst systems for the hydrolytic kinetic resolution of terminal epoxides

Article abstract of DOI:10.1039/c4cy00235k

A heterobimetallic dual-catalyst system based on the preparation and use of various salen complexes has been developed for the hydrolytic kinetic resolution (HKR) of terminal epoxides. A combination of cobalt-salen and manganese-salen complexes, generated from ligands with the same configuration possessing thiophene or pyrrole moieties, produced indeed highly selective catalysts for the hydrolysis of epibromohydrin. This effect could also be extended to other terminal epoxides and to the more challenging ring opening of cyclohexene oxide. Kinetic studies indicated that only one Co^III salen complex was involved in the rate-determining step, which supported a heterobimetallic highly enantioselective pathway based on the crucial existence of in situ generated Co^III-OH species, previously postulated in the literature. The beneficial effect of the presence of additional Mn-complexes was ascribed to the inhibition of the alternative less enantioselective monometallic reaction pathway by epoxide activation.

Full text of DOI:10.1039/c4cy00235k

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Heterobimetallic dual-catalyst systems for the
hydrolytic kinetic resolution of terminal epoxides†
Cite this: Catal. Sci. Technol., 2014,
4, 2608
a
a
ab
*
Xiang Hong, Mohamed Mellah and Emmanuelle Schulz
A heterobimetallic dual-catalyst system based on the preparation and use of various salen complexes has
been developed for the hydrolytic kinetic resolution (HKR) of terminal epoxides. A combination of
cobalt-salen and manganese-salen complexes, generated from ligands with the same configuration
possessing thiophene or pyrrole moieties, produced indeed highly selective catalysts for the hydrolysis of
epibromohydrin. This effect could also be extended to other terminal epoxides and to the more challenging
ring opening of cyclohexene oxide. Kinetic studies indicated that only one CoIII salen complex was involved
in the rate-determining step, which supported a heterobimetallic highly enantioselective pathway based
on the crucial existence of in situ generated CoIII-OH species, previously postulated in the literature. The
beneficial effect of the presence of additional Mn-complexes was ascribed to the inhibition of the alternative
less enantioselective monometallic reaction pathway by epoxide activation.
Received 21st February 2014,
Accepted 15th April 2014
DOI: 10.1039/c4cy00235k
www.rsc.org/catalysis
an undeniable promoting effect (on the selectivity or activity)
Introduction
in the ring-opening catalysis of meso-epoxides by TMSN3.5
A
Inspired by the universal two-metal ion catalysis in enzyme-
promoted reactions,1 the cooperative bimetallic activation
strategy has become an important concept in catalyst design
to achieve enhanced activity and more specific control of the
transition state. In this context, diverse classes of bimetallic
catalysts have been developed in recent times. Jacobsen and
co-workers have discovered several homobimetallic catalytic
systems in asymmetric ring-opening reactions of epoxides with
various nucleophiles.2 In these reactions, the same metal ion
serves not only as the Lewis acid activator for the epoxides but
also as the counter ion for the nucleophiles. Despite their great
performance in catalysis, these homobimetallic catalysts were
limited to the reactions in which the same ligand–metal com-
plex is able to activate both reacting partners. Alternatively,
Shibasaki and coworkers have developed various single-molecular
heterobimetallic catalysts based on chiral binaphthol ligands3
or chiral salen ligands.4 With different heterobimetallic combi-
nations, these catalysts could promote a wide range of asym-
metric transformations with high efficiency. However, in some
cases, the fixation of two metal centers in one single complex
resulted in relatively limited substrate scope. More recently,
Wärnmark and his group published the synthesis of bimetallic
catalysts from C2-symmetric bis-salen ligands and demonstrated
potentially more general principle for cooperative catalysis was
proposed, in which two different chiral complexes activate
both reacting partners in an intermolecular way. This concept
has been independently highlighted by Jacobsen in the appli-
cation of a mixture of (salen)Al and (pybox)Er complexes for
the conjugate cyanation of unsaturated imides6 and also by
Belokon and Kagan in the use of a mixture of (salen)Ti and
(salen)V complexes in the asymmetric trimethylsilylcyanation.7
Hydrolytic kinetic resolution (HKR) is one of the most
powerful reactions for the preparation of enantiopure termi-
nal epoxides.8 Detailed mechanistic investigation showed
that this reaction involves two forms of a salen-CoIII complex:
the initial Lewis acidic CoIII-X complex and the in situ gener-
ated CoIII-OH complex. Both complexes activate cooperatively
and respectively the epoxides and water, even if the suggested
CoIII-OH complex was still neither isolated nor fully character-
ized (Scheme 1).9 Some other reports from Jacobsen's group
also indicated the existence of an alternative less enantio-
selective monometallic pathway in certain cases.10 Very recent
studies have further demonstrated the importance of the cobalt
counter anion nature on the reaction course due to both its
scrambling ability11 and nucleophilicity towards addition to
epoxide.12 Lastly, Jacobsen and coworkers proved by experi-
mental and computational studies that the absolute configu-
ration of both complexes implied in the rate-determining
transition step is of utmost importance (and should be the same)
for efficient catalysis.13
a Equipe de catalyse moléculaire, Université Paris-Sud, ICMMO, UMR8182, 91405
Orsay Cedex, France. E-mail: emmanuelle.schulz@u-psud.fr
b CNRS, 91405 Orsay Cedex, France
† Electronic supplementary information (ESI) available: Synthetic procedures,
copies of GC, HPLC chromatograms, kinetic studies, and NMR spectra. See
DOI: 10.1039/c4cy00235k
During our ongoing studies on the dynamic HKR of epi-
bromohydrin catalyzed by thiophene-modified salen cobaltIII
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Scheme 2 Dynamic HKR of epibromohydrin catalyzed by cobalt-salen
complexes.
Table 1 The effect of different axial ligands on the dynamic HKR of
epibromohydrin catalyzed by salen CoIII complexesa
Entry
Salen-CoIII
eeb (%)
Scheme 1 The proposed mechanism for the HKR of terminal epoxides.8,9
1
2
3
(S,S)-1-CoIII-OAc
(S,S)-1-CoIII-OTs
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OTs
(S,S)-2-CoIII-BF4
(S,S)-3-CoIII-OAc
(S,S)-3-CoIII-OTs
96 (S)
96 (S)
91 (S)
62 (S)
6 (S)
complexes under homogeneous and heterogeneous conditions,
we observed a strong dependence of the enantioselective
performance of the complexes on the nature of their axial
ligands.14 Control experiments and kinetic studies suggested
the existence of a competitive non-enantioselective mono-
metallic pathway in our case, which thus led to a significant
decrease in enantioselectivity.
We report herein further studies on the HKR of terminal
epoxides promoted by a combination of two different thiophene-
modified salen metal complexes, leading to enhanced perfor-
mance in terms of selectivity and highlighting the existence
of two catalytic pathways in this reaction. We furthermore
demonstrate the importance of the configuration of ligands
involved, with respect to each other, in order to obtain opti-
mal enantioselectivities.
4
5c
6c
7
97 (S)
75 (S)
a
Conditions: epibromohydrin (104 μL, 1.21 mmol), salen-Co (0.024 mmol),
THF (145 μL), H2O (33 μL), chlorobenzene (20 μL), 4 °C, 48 h. Conver-
sion >99% determined by GC analysis with chlorobenzene as an inter-
nal standard. b Determined by chiral GC analysis of the corresponding
dimethyl acetal. c Complete conversion was not reached and the product
was isolated in 81% and 75% yield, respectively.
the nature of the axial ligands (Table 1). Complex (S,S)-2-CoIII-OTs
catalyzed the HKR of epibromohydrin with a lower enantio-
meric excess compared to its CoIII-OAc analogue (62% instead
of 91% ee, entries 3 and 4, Table 1). Kinetic studies have thus
been performed in the presence of the (S,S)-2-CoIII-OTs cata-
lyst and resulted indeed in the determination of a reaction
order of about 1.3 for this complex (see the ESI,† sections 5.2
and 5.3). As a comparison, under similar catalytic conditions,
an order of 1.6 was calculated when the reaction was promoted
Results and discussion
Effect of the axial ligands on the dynamic HKR of
epibromohydrin
Epibromohydrin was chosen as a model substrate for this
study; it undergoes very fast racemization under the HKR con-
ditions and the resulting diol can consequently be obtained
by complete conversion since, in this case, kinetic hydrolytic
resolution proceeds in dynamic mode (Scheme 2). Jacobsen
and his group reported that 3-bromo-propane-1,2-diol was iso-
lated in 93% yield and 96% ee, with 1.5 equiv. of H2O in THF,
in the presence of 2 mol% of (S,S)-1-CoIII-OAc.15
As we have previously reported, the axial ligands have no
observable influence on the enantioselective performance of
Jacobsen's salen CoIII complexes derived from ligand 1 under
our reaction conditions (entries 1 and 2, Table 1). We how-
ever found that for the catalysts in which tert-butyl groups
on the 5,5′-positions of these complexes were modified by
the more electron-deficient thienyl groups (entries 3, 4 and 5)
or pyrrole groups (entries 6 and 7) (see structures 2 and 3 in
Scheme 3), the enantioselectivity became strongly dependent on
Scheme 3 The structure of the salen ligands used in this study.
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by (S,S)-2-CoIII-OAc, which delivered the target product in
91% ee (entry 3, Table 1). The stronger Lewis acidity resulting
from the presence of the tosyl axial ligand seems, in this case,
to play an important role in the catalytic performance of
(S,S)-2-CoIII-OTs.12 Therefore, in the transformations promoted
by both catalysts, indeed, the monometallic route plays an
undeniable role, which is more pronounced when the cobalt
center bears a tosylate counter anion. Complex (S,S)-2-CoIII-BF4
was also prepared and tested in the HKR of epibromohydrin
as we have already reported.14
observed depending on the nature of the added metal com-
plex, and the desired product could be isolated with enantio-
meric excesses varying from 56 to 96% (Table 2). These
variations in the enantioselectivity indicate clearly that the
chiral additives are involved in the catalytic cycle of the HKR
together with the salen CoIII complex, as they were all inactive
in HKR alone. Among all of the tested species,18 the use of
complex (S,S)-2-MnIII-Cl as an additive delivered the targeted
product with the highest enantioselectivity, up to 96% (compare
entry 1 with entry 7, Table 2).
This complex is an active catalyst promoting the transfor-
mation with a satisfying yield (81%), but the resulting diol
was isolated in its nearly racemic form (entry 5, Table 1).
Kinetics delivered a reaction order of 1.0 for this catalyst bearing
a non-nucleophilic BF4 axial ligand (see the ESI,† section 5.4).
This result confirms the important effect of the nature of the
axial ligand; in the latter case, hydrolysis of the complex could
not take place and the monometallic, non-enantioselective
catalyst path is consequently preferred.16
The same type of experiment was performed by using
N-boc-pyrrole-derived salen ligand 3, possessing more-electron
donating substituents.14 The corresponding (S,S)-3-CoIII-OAc
complex displayed delightfully a similar enantioselectivity to
Jacobsen's complex, but the corresponding catalyst bearing a
tosylate group as an axial ligand showed again a decreased
selectivity, indicating that the monometallic pathway still exists
in the latter case (entries 6 and 7, Table 1).
Moreover, the use of other additional Mn salts did not show
any influence on the catalysis promoted by (S,S)-2-CoIII-OAc in
the transformation (entries 8 and 9, Table 2). (S,S)-2-MnIII-Cl
was also tested as an additive in the dynamic HKR of epi-
bromohydrin catalyzed by complex (S,S)-2-CoIII-OTs. A signifi-
cant increase of the enantiomeric excess from 62 to 94% was
observed (entries 10 and 11, Table 2). Based on the mecha-
nism proposed by Jacobsen, these results prompted us to pro-
pose a rational reaction scheme for the HKR promoted by a
dual-catalyst system, in which salen MnIII serves as an epoxide
activator and catalyzes the HKR together with the CoIII-OH
species generated from the salen CoIII complexes by hydro-
lysis (Scheme 4). In this case, the addition of a salen Mn com-
plex has probably effectively reduced the non-enantioselective
monometallic pathway, which takes place in a non-negligible way
in the sole presence of thiophene-modified cobalt complexes.
Influence of the ligand structure on the dual-catalyst system
In order to confirm our hypothesis about the existence of a
dual catalytic system, we performed additional catalytic
experiments to identify the origin of the match effect. Various
salen-containing MnIII complexes, differing not only in the
structure but also in the configuration of the involved ligand,
were further engaged in the HKR catalyzed by salen CoIII-OAc
complexes to test the reliability of the proposed mechanism.
The results are summarized in Table 3.
Dynamic HKR of epibromohydrin with additional salen
metal complexes
To minimize the monometallic pathway and gain further
insight into the mechanism of HKR, we wondered if we could
replace the Lewis acidic CoIII-X complex in the classic cata-
lytic system by other chiral epoxide activators. Several other
salen complexes have been reported which are able to cata-
lyze epoxide-opening reactions as Lewis acids.17 These com-
plexes were thus synthesized according to the reported
procedures from the same thiophene-modified salen ligand,
(S,S)-2, from aluminum, manganese, chromium, vanadium or
titanium precursors. Control experiments were conducted to
test their ability to promote the HKR of epibromohydrin under
the same conditions as those used with the cobalt catalysts,
but all of them (see the ESI,† section 4, Table 1, entries 1–11)
were found to be inactive, when engaged alone. They were
consequently used as additives into the HKR catalyzed by
thiophene-salen CoIII complexes.
Table 2 The effect of chiral salen metal complexes as additives on the
dynamic HKR of epibromohydrin catalyzed by salen CoIII complexesa
Entry
Salen-CoIII
Additive
eeb (%)
1
2
3
4
5
6
7
8
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OTs
(S,S)-2-CoIII-OTs
—
91 (S)
94 (S)
95 (S)
85 (S)
56 (S)
88 (S)
96 (S)
85 (S)
91 (S)
62 (S)
94 (S)
(S,S)-2-CrIII-Cl
(S,S)-2-AlIII-Cl
(S,S)-2-VIVO
(S,S)-2-VVO(OiPr)c
(S,S)-2-TiIV(OiPr)2
(S,S)-2-MnIII-Cl
Mn(OAc)2·4H2O
MnCl2
c
Salen CoIII-OAc complexes were reported to undergo irre-
versible hydrolysis during the HKR to produce salen CoIII-OH
species involved in the catalytic process.12 (S,S)-2-CoIII-OAc
was thus used as a precursor of (S,S)-2-CoIII-OH and tested as
a catalyst combined with other salen metal complexes sup-
posed to be involved only as epoxide activators. Both metallic
complexes were introduced in equivalent catalytic quantities,
with the reaction performed otherwise under the same condi-
tions. Different levels of “match” or “mismatch” effects were
9
10
11
—
(S,S)-2-MnIII-Cl
a
Conditions: epibromohydrin (104 μL, 1.21 mmol), salen-Co (0.024 mmol),
additive (0.024 mmol), THF (145 μL), H2O (33 μL), chlorobenzene
(20 μL), 4 °C, 48 h. Conversion determined by GC analysis with chloro-
b
benzene as an internal standard, >99% in all cases. Determined by
c
chiral GC analysis of the corresponding dimethyl acetal. Generated
in situ according to reported procedures.17
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(S,S)-4-MnIII-Cl was used in the reaction catalyzed by complex
(R,R)-2-CoIII-OAc (entry 7, Table 3). These results confirm
once more the involvement of the additive in the selectivity-
determining transition state and also show that the chiral
structure of the additive complex is not trivial. Moreover, it
was verified that these results are not temperature dependent
since exactly the same trends could be observed by using
similar Co- and Mn-salen combinations at room temperature
(entries 8–11, Table 3). Accordingly, when complex rac-4-MnIII-Cl
was used, the target product was isolated with an ee exactly
resulting from the average of the values obtained in the pres-
ence of each enantiomerically pure Mn complex (entry 12,
Table 3). Delightfully the addition of (S,S)-2-MnIII-Cl to
N-boc-pyrrole-derived salen complex (S,S)-3-CoIII-OAc produced
the product in its nearly enantiopure form (entry 13, Table 3)
as another positive “match” effect. Jacobsen's salen MnIII
complex from (S,S)-1 has also been added to the reaction
catalyzed by complex (S,S)-1-CoIII-OAc. In this case too, a
“match” effect has been observed, although in a lower extent
(98% vs. 96% ee), (see the ESI,† section 4, Table 1, entries 15–19).
This justifies the use of the thiophene-modified salen com-
plexes to better highlight these effects.
Scheme 4 The mechanism proposed for the HKR catalyzed by the
dual-catalyst systems.
Table 3 Dynamic HKR of epibromohydrin catalyzed by a dual-catalyst
system consisting of salen CoIII and salen MnIII complexesa
Entry
Salen-CoIII
Additive
T (°C)
eeb (%)
1
2
3
4
5
6
7
8
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(R,R)-2-CoIII-OAc
(R,R)-2-CoIII-OAc
(R,R)-2-CoIII-OAc
(R,R)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-2-CoIII-OAc
(S,S)-3-CoIII-OAc
(S,S)-1-MnIII-Cl
(S,S)-4-MnIII-Cl
(R,R)-4-MnIII-Cl
—
4
4
4
4
4
4
4
20
20
20
20
20
4
96 (S)
98 (S)
91 (S)
91 (R)
96 (R)
98 (R)
91 (R)
87 (S)
94 (S)
96 (S)
87 (S)
91 (S)
>99 (S)
Origin of the dual-catalyst “match” effect
(R,R)-2-MnIII-Cl
(R,R)-4-MnIII-Cl
(S,S)-4-MnIII-Cl
—
Belokon and North reported that some salen complexes can
undergo dynamic ligand exchange under certain conditions.19
To examine whether the relatively more significant “match”
effect observed in the presence of complex 4-MnIII-Cl resulted
from an exchange of salen ligands when it was used in addi-
tion to (S,S)-2-CoIII-OAc, a CoIII-OAc complex has been pre-
pared from ligand (S,S)-4. Engaged in the dynamic HKR of
epibromohydrin, this complex showed only moderate enantio-
selectivity under the same reaction conditions producing the
product with 64% ee (and only 30% conversion). This test
clearly indicates that salen ligand exchange to a great extent
may not be responsible for the ee enhancement under the
dual catalysis conditions. In this case also, the addition of
(S,S)-4-MnIII-Cl to this reaction resulted in an expected obvious
“match” effect (75% ee).
Nevertheless, and in each studied case, a “match” combina-
tion of both metallic complexes resulted exclusively from the
arrangement of species bearing ligands possessing the same
configuration. We propose that the “head-to-tail” organization,
necessary for obtaining high enantioselectivities, is only feasi-
ble under these conditions.20 The ligand configuration of both
CoIII and MnIII complexes is thus of utmost importance to affect
the reaction outcome of the HKR, which supports our hypothesis
that these two complexes are both engaged in the selectivity-
determining transition state for the formation of the product
(Scheme 5). Such influence of the absolute stereochemistry of
the involved salen ligand/complexes has been very recently
highlighted by Jacobsen and his group and is further demon-
strated here through the use of the dual-catalyst system.13
The role of both complexes in the rate-determining step of
the HKR has been further confirmed by additional experiments
9
(S,S)-2-MnIII-Cl
(S,S)-4-MnIII-Cl
(R,R)-4-MnIII-Cl
Rac-4-MnIII-Cl
(S,S)-2-MnIII-Cl
10
11
12
13
a
Conditions: epibromohydrin (104 μL, 1.21 mmol), salen-Co (0.024 mmol),
additive (0.024 mmol), THF (145 μL), H2O (33 μL), chlorobenzene
(20 μL), 4 °C or 20 °C, 48 h. Conversion determined by GC analysis with
chlorobenzene as an internal standard, >99% in all cases, if no other
b
indication. Determined by chiral GC analysis of the corresponding
dimethyl acetal.
The salen (S,S)-1-MnIII-Cl complex prepared from Jacobsen's
ligand was firstly tested in the dynamic HKR of epi-
bromohydrin catalyzed by complex (S,S)-2-CoIII-OAc, showing
a similar “match” effect in comparison with that of complex
(S,S)-2-MnIII-Cl (entry 1, Table 3 vs. entry 7, Table 2). When a
salen MnIII-Cl complex prepared from ligand (S,S)-4 was used
with thiophene-modified salen complex (S,S)-2-CoIII-OAc, an
even more significant “match” effect was observed (entry 2,
Table 3). These reactions have been repeated by reversing the
configuration of both salen CoIII and the salen MnIII com-
plexes. The product was obtained possessing the opposite
absolute configuration with similar “match” effects (entries 4
to 6, Table 3).
However, when complex (R,R)-4-MnIII-Cl was also engaged
in the reaction catalyzed by complex (S,S)-2-CoIII-OAc, neither
“match” nor “mismatch” effects were observed (entry 3,
Table 3). The same result was also obtained when complex
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of (S,S)-2-CoIII-BF4 together with (S,S)-2-Mn-BF4 proved to be
active (90% conversion) but not enantioselective (6% ee) for
this transformation.
Other kinetic studies have been attempted to gain more
insight into the mechanism of the HKR catalyzed by the new
dual-catalyst systems. The rate equation for the dynamic
HKR of epibromohydrin catalysed by mixtures of two com-
plexes could be represented as:
III n
V = k1[CoIII-OH][CoIII-X] + k2[Co ] [MnIII-Cl]m
tot
Scheme 5 Proposed assembly model for “match” and “mismatch”
interactions between cobalt and manganese complexes, as a dual-catalyst
system.
with
[CoItoIIt] = [CoIII-OH] + [CoIII-X]
involving racemic or achiral salen CoIII complexes. Racemic com-
plex rac-2-CoIII-OAc and achiral complex 5-CoIII-OAc (see Scheme 3)
were both tested in the dynamic HKR of epibromohydrin in
the presence of various enantiopure chiral salen MnIII com-
plexes, and as expected, products with undeniable enantio-
meric excesses could be isolated in each case (entries 2 to 5, 7
and 8, Table 4). These results are also not in favor of extensive
ligand exchange in this reaction.
To simplify the rate equation and since the concentration
of the (S,S)-2-CoIII-OH species is not accessible, complex
(S,S)-2-Mn-Cl was used in excess (2 mol%) compared to the
cobalt complex (0.05 to 0.2 mol%). Under these conditions,
the first part of the equation rate can be neglected to yield
V = K[CoIII n
tot] . The conversion vs. time plots obtained under
these conditions are reported in Scheme 6, after a period
of 4 h.21 The rate of each reaction could be calculated from
the above plots, and the value of n has been determined by
the log V/log[CoItoIIt] plot (Scheme 7).
A first order dependence on the concentration of complex
CoIII has thus been determined for the reaction rate (n = 0.9921),
Complex (S,S)-2-CoIII-BF4 has been reported as a non-
enantioselective catalyst for the HKR of epibromohydrin
(entry 5, Table 1). Astonishingly, the use of (S,S)-2-MnIII-Cl
as an additive furnished the target product in a nearly quan-
titative yield and with 87% ee. On the contrary, addition of
(R,R)-2-MnIII-Cl has no effect on the reaction promoted by
(S,S)-2-CoIII-BF4. The formation of the enantio-enriched prod-
uct must then arise from a bimetallic pathway, but Co-BF4
species are not known to yield the crucial Co-OH activator.
We propose that in this case, an axial ligand exchange may
occur between the Mn-Cl species and the Co-BF4 complex,
producing a nucleophilic Co-Cl catalyst. This exchange is
nonetheless only possible if a match heterobimetallic species
is formed between complex bearing ligands possessing the
same configuration. Then as expected, an equimolar mixture
Scheme 6 Conversion/time plots for the dynamic HKR of epibromohydrin
catalysed by mixtures of (S,S)-2-MnIII-Cl (2 mol%) and (S,S)-2-CoIII-OAc
(0.05–0.2 mol%) after a time of 4 h.
Table 4 Dynamic HKR of epibromohydrin catalyzed by a dual-catalyst
system consisting of racemic or achiral salen CoIII and chiral salen MnIII
complexesa
Entry
Salen-CoIII
Additive
eeb (%)
1
2
3
4
5
6
7
8
Rac-2-CoIII-OAc
Rac-2-CoIII-OAc
Rac-2-CoIII-OAc
Rac-2-CoIII-OAc
Rac-2-CoIII-OAc
5-CoIII-OAc
—
0
(S,S)-2-MnIII-Cl
(S,S)-3-MnIII-Cl
(R,R)-2-MnIII-Cl
(R,R)-3-MnIII-Cl
—
20 (S)
24 (S)
20 (R)
24 (R)
0
5-CoIII-OAc
(S,S)-2-MnIII-Cl
(S,S)-3-MnIII-Cl
15 (S)
7 (S)
5-CoIII-OAc
a
Conditions: epibromohydrin (104 μL, 1.21 mmol), salen-Co (0.024 mmol),
additive (0.024 mmol), THF (145 μL), H2O (33 μL), chlorobenzene
(20 μL), 20 °C, 48 h. Conversion determined by GC analysis with chloro-
benzene as an internal standard, >99% in all cases. Determined by
chiral GC analysis of the corresponding dimethyl acetal.
III
tot
b
Scheme 7 The log V/log[Co ] plot for the dynamic HKR of epibromohydrin
catalysed by mixtures of (S,S)-2-MnIII-Cl and (S,S)-2-CoIII-OAc.
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which is totally different from the homobimetallic mechanism
of the classic monocatalyst system. Salen MnIII complexes have
also been added to reactions in which salen CoIII-OAc was pre-
viously deactivated by excess epoxide, and a rate-acceleration
effect has been observed. Unfortunately all our efforts to pre-
pare a pure CoIII-OH complex have failed. The reaction order
according to the concentration of the Mn complex could thus
not be determined because of the absence of totally inactive
CoIII complexes as Lewis acids for the HKR. The effect of the
Mn complex quantity on the enantioselectivity of the transfor-
mation has been evaluated, and it was demonstrated that the
highest value was obtained for an exact 1/1 mixture of Co/Mn
complexes (Table 5). This mechanistic approach indeed puts
forward a heterobimetallic transition state to occur for the
HKR catalyzed by dual-catalyst system Co/Mn.
Scheme 8 Asymmetric hydrolysis of cyclohexene oxide.
application, and the results are presented in Table 6. For
2-phenoxymethyl oxirane and 2-allyloxymethyl oxirane, which
could be selectively resolved by complex (S,S)-2-CoIII-OAc, the
addition of complex (S,S)-2-MnIII-Cl to the reaction resulted in
greatly enhanced enantioselectivities (entries 2 and 4 vs. entries 1
and 3, Table 6). The dual-catalyst system also showed advan-
tageous enantioselectivity in the HKR of 2-phenyl-oxirane in
comparison with the monocatalyst system (entry 6 vs. entry 5,
Table 6), even if the “match” effect was relatively less obvious
in this case.
The efficiency of the dual Co/Mn catalyst system was also
evaluated in the asymmetric hydrolysis of more challenging
disubstituted epoxides.22 For the transformation of cyclohexene
oxide, the dual-catalyst system prepared from (S,S)-2-CoIII-OAc
and (S,S)-2-MnIII-Cl proved interestingly to be much more
enantioselective than the classic cobalt-promoted monocatalyst
system (Scheme 8). In all these cases, the new dual-catalyst
system proved to be more enantioselective than the mono-
catalyst system for the HKR of terminal epoxides.
HKR of other epoxides with the dual-catalyst system
This dual-catalyst system has also been finally tested in the
HKR of other terminal epoxides to determine the scope of its
Table 5 Influence of the (S,S)-4-MnIII-Cl quantity (x mol%) on the
enantioselectivity of the HKR of epibromohydrin catalysed by (S,S)-2-
CoIII-OAc (2 mol%)a
Entry
X (mol%)
eeb (%)
1
2
3
4
5
0
0.4
1
2
4
91 (S)
95 (S)
96 (S)
98 (S)
98 (S)
Conclusion
a
Conditions: epibromohydrin (104 μL, 1.21 mmol), salen-Co (0.024 mmol),
additive (x mol%), THF (145 μL), H2O (33 μL), chlorobenzene (20 μL),
4 °C, 48 h. Conversion determined by GC analysis with chlorobenzene
We have thus developed a novel heterobimetallic dual-
catalyst system for the HKR of terminal epoxides involving
heteroaromatic-modified salen complexes, which showed
enhanced enantioselectivities by reducing the alternative less-
enantioselective monometallic pathway that may be predomi-
nant with these ligands. This catalytic system is clearly not
competing with previously described very efficient complexes
in this reaction, but it allows gaining some insight into
the mechanism of the HKR reaction. Kinetic studies showed
that only one salen CoIII complex was involved in the rate-
determining step of the HKR in this case, which supported
the existence of the CoIII-OH species proposed by Blackmond
and Jacobsen, but not yet precisely characterized. For obtaining
high enantioselectivities in the dual-catalyst system, we have
demonstrated that both metallic complexes must possess the
same ligand configuration to yield the optimized shape in the
selectivity-determining transition state for the formation of
the product. Counter anion scrambling took place between
non-enantioselective CoIII-BF4 and non-active MnIII-Cl to pro-
duce an efficient enantioselective dual catalyst. This axial
ligand exchange is nonetheless only possible if a “match”
heterobimetallic species is formed between complex bearing
ligands possessing the same configuration. Applied in the
HKR of other terminal epoxides, the heterobimetallic dual-
catalyst system exhibited greatly enhanced enantioselectivities
b
as an internal standard, >99% in all cases. Determined by chiral
GC analysis of the corresponding dimethyl acetal.
Table 6 HKR of other epoxides catalyzed by the dual Co and Mn
catalyst systema
Additive
(mmol)
T
Convb
(h) (%)
eec
(%)
eed
(%)
e
Entry
Krel
1
2
0
16
16
54
51
99
99
83
94
60
289
0.024
3
4
5
6
0
16
16
96
96
53
51
60
57
98
99
96
97
85
94
65
74
58
133
17
0.024
0
0.024
25
a
Conditions: epoxide (1.21 mmol), (S,S)-2-CoIII-OAc (0.024 mmol),
(S,S)-2-MnIII-Cl as additives (0 or 0.024 mmol), 4 °C. Determined by
GC analysis with chlorobenzene as an internal standard. ee of the
epoxides determined by chiral GC or HPLC analyses. ee of the diols
determined by chiral GC or HPLC analysis. Calculated by equation:
b
c
d
e
krel = ln[(1 − c)(1 − ee)]/ln[(1 − c)(1 + ee)].
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and it thus opens interesting prospects for more challenging
substrates. Further efforts to investigate the detailed mecha-
nism and to explore other activities of these heterobimetallic
dual-catalyst systems are ongoing.
[α]20 − 1.54 (c 1.04, CHCl3). UV-vis (CH3CN) λmax 221, 259,
294, 349 nm.
Preparation of ligand 5
A solution of 3-tert-butyl-2-hydroxy-5-(thiophen-2-yl)benzaldehyde
(500 mg, 1.92 mmol) and 1,2-ethylene-1,2-diamine (58 mg,
0.96 mmol) in dry ethanol (30 mL) was stirred at 60 °C for
3 h. After removal of the solvents under reduced pressure,
ligand 5 was obtained as a yellow solid (495 mg, 95%) and
Experimental section
General information
All reactions were conducted in glassware under magnetic
stirring. The epoxides and 2,2-dimethoxy-propane were pur-
chased from Aldrich and used directly without further purifi-
cation. 3-tert-Butyl-2-hydroxy-5-(thiophen-2-yl)benzaldehyde,
N,N′-bis(3-tert-butylsalicylidene-5-(thiophen-2-yl))-cyclohexane-
1,2-diamine 2, (S,S)-(N,N′-bis(3-tert-butylsalicyl-idene-5-(N-boc
pyrrol-2-yl)-cyclohexane-1,2-diamine 3 and the corresponding
cobalt complexes were prepared by previously reported proce-
dures.23 THF was distilled from sodium/benzophenone and
DCM was distilled from CaH2 before use. 1H NMR spectra
and 13C NMR spectra were recorded using a Bruker AM 360
(360 MHz), AM 300 (300 MHz) or AM 250 (250 MHz) instru-
ment and data are reported in ppm with the solvent signal as
the reference. IR spectra were recorded as KBr disks using a
Perkin-Elmer spectrometer. UV-vis spectra were obtained using
a Bio-TEK UNIKON XL spectrometer. Optical rotations were
measured using a Perkin-Elmer 241 digital polarimeter with a
sodium (489 nm) lamp. The HRMS analyses were performed
with MicroTOFq (quadrupole coupled with TOF analyzer). Chiral
gas chromatography (GC) analyses were performed using
Fisons instrument GC 8000 equipped with FID detectors and
a chiraldex β-PM chiral capillary column (50 m × 0.25 mm)
using hydrogen as carrier gas. Achiral gas chromatography
(GC) analyses were performed using a Varian 430-GC gas chro-
matograph. Chiral high performance liquid chromatography
(HPLC) analyses were performed using a Perkin-Elmer chro-
matograph equipped with a diode array UV detector. Elemen-
tal analysis was performed by the National Analytical Centre
of Scientific Research in Solaize. For low temperature studies,
an Oxford Instrument continuous-flow liquid helium or nitro-
gen cryostat and a temperature control system were used.
1
determined to be pure by NMR analysis. H NMR (360 MHz,
CDCl3) δ 13.90 (s, 2H), 8.42 (s, 2H), 7.54 (d, J = 2.2 Hz, 2H),
7.31 (d, J = 2.2 Hz, 2H), 7.17 (dd, J = 5.0 et 1.0 Hz, 2H), 7.14
(dd, J = 3.6 et 1.0 Hz, 2H), 7.02 (dd, J = 5.0, 3.6 Hz, 2H), 3.66
(s, 4H), 1.44 (s, 18H). 13C NMR (90 MHz, CDCl3) δ 167.3 (CH),
160.4 (Cq), 144.7 (Cq), 138.3 (Cq), 138.0 (Cq), 128.1 (CH),
128.0 (CH), 127.4 (CH), 123.8 (CH), 122.1 (CH), 118.8 (Cq),
59.5 (CH2), 35.2 (Cq), 29.5 (CH3). HRMS (ESI†): calcd for
C32H37O2N2S2 (M + H) 545.2291, found 545.2265. IR (KBr,
ν (cm−1)) 3413, 2955, 2903, 2867, 2580, 1635, 1466, 1446, 1425,
1270, 1163, 704, 693. m.p. 205–207 °C. UV-vis (CH3CN) λmax
299, 351, 479 nm.
Preparation of complex 4-CoII
To a solution of N,N′-bis(3-tert-butylsalicylidene-5-(thiophen-2-yl))-
1,2-diphenylethylene-1,2-diamine (500 mg, 0.72 mmol) in degassed
DCM (2.6 mL), a solution of Co(OAc)2·4H2O (216 mg, 0.86 mmol)
in degassed MeOH (2.6 mL) was added under continuous stir-
ring. The resulting mixture was stirred for 90 min at room
temperature and then 30 min at 0 °C. After filtration under
reduced pressure, the residue was washed with cold MeOH
(20 mL) and then recrystallized in a mixture of DCM and
MeOH (1 : 1) to yield the desired complex (542 mg, >95%) as
a dark red powder. HRMS (ESI†): calcd for C44H43O2N2S2Co
(M + H) 754.2014, found 754.2013. IR (KBr, ν (cm−1)) 3437,
3065, 3029, 3005, 2952, 2909, 2867, 2379, 2346, 1597, 1523,
1423, 1406, 1322, 1250, 1207, 1170, 696. [α]20 − 1741 (c 0.002,
CHCl3). UV-vis (CHCl3): λmax 240, 276, 308, 406, 431 nm.
Preparation of complex 4-CoIII-OAc
Preparation of ligand 4
To a solution of complex 4-CoII (200 mg, 0.27 mmol) in THF
(50 mL), acetic acid (0.2 mL, 35 mmol) was added under con-
tinuous stirring. The solution was stirred vigorously for 18 h
in air at room temperature before the solvents were removed
under reduced pressure. Finally 3 × 20 mL of toluene was
added and then removed under reduced pressure to afford
the desired complex (187 mg, 87%) as a brown powder, which
was used without further purification. HRMS (ESI†): calcd for
C44H42O2N2S2Co (M-OAc) 753.2014, found 753.2012. IR (KBr,
ν (cm−1)) 3423, 2951, 2908, 2364, 1608, 1590, 1523, 1405, 1322,
1250, 1171, 696. [α]20 − 1260 (c 0.003, CHCl3). UV-vis (CHCl3):
λmax 240, 275, 310, 406, 431 nm.
A solution of 3-tert-butyl-2-hydroxy-5-(thiophen-2-yl)benzaldehyde
(350 mg, 1.34 mmol) and 1,2-diphenylethylene-1,2-diamine
(148 mg, 0.7 mmol) in dry ethanol (13 mL) was stirred at
60 °C for 3 h. After removal of the solvents under reduced
pressure, ligand 4 was obtained as a yellow solid (374 mg,
1
>95%) and determined to be pure by NMR analysis. H NMR
(250 MHz, CDCl3) δ 13.93 (s, 2H), 8.40 (s, 2H), 7.49 (d, J =
2.3 Hz, 2H), 7.18–7.27 (m, 14H), 7.09 (d, J = 4.0, 2H), 7.03
(dd, J = 4.5, 4.0 Hz, 2H), 4.77 (s, 2H), 1.45 (s, 18H). 13C NMR
(62.5 MHz, CDCl3) δ 166.9 (CH), 160.1 (Cq), 144.6 (Cq), 139.3
(Cq), 138.0 (Cq), 128.6 (CH), 128.1 (CH), 127.9 (CH), 127.8
(CH), 127.6 (CH), 124.7 (Cq), 123.7 (CH), 122.0 (CH), 118.6
(Cq), 80.2 (CH), 35.0 (Cq), 29.4 (CH3). HRMS (ESI†) calcd for
C44H45O2N2S2 (M + H) 697.2923, found 697.2935. IR (KBr,
ν (cm−1)) 3414, 2956, 2918, 2863, 1628, 1454, 1426. m.p. 122–124 °C.
Preparation of complex 5-CoII
To a solution of N,N′-bis(3-tert-butylsalicylidene-5-(thiophen-2-yl))-
ethylene-1,2-diamine (300 mg, 0.55 mmol) in degassed DCM
2614 | Catal. Sci. Technol., 2014, 4, 2608–2617
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(10 mL), a solution of Co(OAc)2·4H2O (165 mg, 0.66 mmol) in
degassed MeOH (4 mL) was added under continuous stirring.
The resulting mixture was stirred for 90 min at room tempera-
ture and then 30 min at 0 °C. After filtration under reduced
pressure, the residue was washed with cold MeOH (20 mL)
and then recrystallized in a mixture of DCM and MeOH (1 : 1)
to afford the desired complex (315 mg, 95%) as a black pow-
der. HRMS (ESI†): calcd for C32H35O2N2S2Co 602.1388, found
602.1376. IR (KBr, ν (cm−1)) 3850, 3737, 2948, 2365, 2346,
1598, 1533, 1406, 1385, 1315, 1208, 1172, 691. UV-vis (CH3CN)
λmax 425, 401, 321 nm.
7.32 (d, J = 3.3 Hz, 2H), 7.10 (dd, J = 4.0, 2H), 3.35–3.45
(m, 2H), 2.55–2.65 (m, 4H), 1.9–2.0 (m, 4H), 1.57 (s, 18H).
HRMS (ESI†): calcd for C36H40O2N2S2Al (M-Cl) 623.2341, found
623.2322. IR (KBr, ν (cm−1)) 3391, 2947, 1633, 1552, 1415, 1353,
1326, 1317, 1259, 1171, 821. [α]20 + 50.4 (c 0.18, CHCl3).
Preparation of complex 2-MnIII-Cl
To a solution of (N,N′-bis(3-tert-butylsalicylidene-5-(thiophen-2-yl))-
cyclo-hexane-1,2-diamine (0.6 g, 1.0 mmol) in degassed tolu-
ene (2.8 mL), a solution of Mn(OAc)2·4H2O (735 mg, 3 mmol)
in degassed EtOH (5.6 mL) was added with continuous stir-
ring under an argon atmosphere. The resulting mixture was
heated to reflux at 85 °C for 5 h and then a saturated solution
of NaCl in water (5 mL) was added under an air atmosphere.
The mixture was further stirred in air for 18 h then par-
titioned between 50 mL of water and 50 × 2 mL of DCM. The
combined extracts were washed with water (40 mL × 3) and a
saturated solution of NaCl (40 mL × 3) and then dried over
Na2SO4. After removal of the solvents under reduced pressure,
the desired complex was obtained as a dark brown powder
(436 mg, 63%). HRMS (ESI†): calcd for C36H40O2N2S2Mn
651.1912, found 651.1903. IR (KBr, ν (cm−1)) 3420, 2949, 2866,
1612, 1543, 1408, 1313, 1171, 816, 734, 693, 574. [α]20 + 1376
(c 0.01, CHCl3). UV-vis (CHCl3): λmax 238, 307, 457 nm.
Preparation of complex 5-CoIII-OAc
To a solution of complex 5-CoII (150 mg, 0.27 mmol) in THF
(50 mL), acetic acid (0.2 mL, 35 mmol) was added under con-
tinuous stirring. The solution was stirred vigorously for 18 h
in air at room temperature before the solvents were removed
under reduced pressure. Finally 3 × 20 mL of toluene was
added and then removed under reduced pressure to afford
the desired complex (90 mg, 52%) as a brown powder, which
was used without further purification. HRMS (ESI†): calcd for
C32H34O2N2S2Co (M-OAc) 601.1388, found 601.1405. IR (KBr,
ν (cm−1)) 3436, 2949, 2865, 1640, 1608, 1408, 1330, 1163, 688.
UV-vis (CHCl3): λmax 289, 325, 426 nm.
Preparation of complex 2-CrIII-Cl
Preparation of complex 4-MnIII-Cl
To a solution of N,N′-bis(3-tert-butylsalicylidene-5-(thiophen-2-yl))-
cyclohexane-1,2-diamine (1 g, 1.67 mmol) in degassed THF
(20 mL), a solution of CrCl2 (236 mg, 1.92 mmol) in degassed
THF (40 mL) was added with continuous stirring under an
argon atmosphere. The resulting mixture was stirred under
argon at room temperature for 2 h and then stirred under an
air atmosphere overnight. The mixture was further washed
with a saturated solution of NH4Cl in water (60 mL) and a sat-
urated solution of NaCl (60 mL × 3) and then dried over
Na2SO4. After removal of the solvents under reduced pressure,
the desired complex was obtained as a brown powder (1.22 g,
>95%). Anal. calcd for C36H40N2O2S2CrCl-THF: C, 63.52;
H, 6.40; N, 3.70; S, 8.48%. Found C, 63.72; H, 6.64; N, 3.77;
S, 8.43%. IR (KBr, ν (cm−1)) 2939, 2860, 1620, 1536, 1459,
To a solution of N,N′-bis(3-tert-butylsalicylidene-5-(thiophen-2-yl))-
1,2-diphenylethylene-1,2-diamine (315 mg, 0.45 mmol) in
degassed toluene (1.4 mL), a solution of Mn(OAc)2·4H2O
(333 mg, 1.36 mmol) in degassed EtOH (2.8 mL) was added
with continuous stirring under an argon atmosphere. The
resulting mixture was heated to reflux at 85 °C for 5 h and
then a saturated solution of NaCl in water (5 mL) was added
under an air atmosphere. The mixture was further stirred in air
for 18 h then partitioned between 30 mL of water and 30 × 2 mL
of DCM. The combined extracts were washed with water
(20 mL × 3) and a saturated solution of NaCl (40 mL × 3) and
then dried over Na2SO4. After removal of the solvents under
reduced pressure, the desired complex was obtained as a
dark brown powder (213 mg, 60%). HRMS (ESI†): calcd for
C44H42O2N2S2Mn 749.2063, found 749.2052. IR (KBr, ν (cm−1))
3436, 2954, 2924, 2863, 1608, 1537, 1408, 1311, 1248, 1206,
1171, 816, 741, 697, 574. [α]20 + 536 (c 0.012, CHCl3). UV-vis
(CHCl3): λmax 239, 308, 465 nm.
1420, 1385, 1323, 1254, 1206, 1160, 878, 813, 688, 558. [α]20
+
1035 (c 0.03, CHCl3). UV-vis (CHCl3): λmax 227, 278, 310, 445 nm.
Preparation of complex 2-AlIII-Cl
To a solution of N,N′-bis(3-tert-butylsalicylidene-5-(thiophen-2-yl))-
cyclohexane-1,2-diamine (300 mg, 0.5 mmol) in dry DCM
(4 mL), a solution of diethyl aluminum chloride (0.5 mmol) in
toluene was added slowly with continuous stirring under an
argon atmosphere. The resulting mixture was stirred under
argon at room temperature for 2 h. After removal of the sol-
vents under reduced pressure, the resulting yellow solid was
rinsed with 20 mL of hexane. The desired complex was dried
under vacuum and obtained as a yellow powder (329 mg,
Preparation of complex 2-VIVO
To
a
solution of (S,S)-(N,N′-bis(3-tert-butylsalicylidene-
5-(thiophen-2-yl)-cyclohexane-1,2-diamine (500 mg, 0.84 mmol)
in CHCl3 (12 mL), a solution of VOSO4·5H2O (633 mg, 2.5 mmol)
in water (5 mL) was added with continuous stirring under an
argon atmosphere. A solution of Et3N (260 μL, 1.86 mmol) in
EtOH (7 mL) was then added to the resulting mixture slowly
over 2 h and the resulting mixture was stirred at room tem-
perature for a further 20 h. After an extraction with DCM
(30 mL × 2), the combined extracts were washed with water
1
>95%). H NMR (360 MHz, DMSO) δ 8.46 (s, 2H), 7.76 (d, J =
2.5 Hz, 2H), 7.62 (d, J = 2.5 Hz, 2H), 7.42 (d, J = 5 Hz, 2H),
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(30 mL × 3) and dried over Na2SO4. The majority of the sol-
vents was removed under reduced pressure and then pentane
was added to precipitate the desired complex as a green pow-
der (362 mg, 65%). HRMS (ESI†) calcd for C36H40O3N2S2V
686.1804, found 686.1812. IR (KBr, ν (cm−1)) 3787, 3423,
2943, 2866, 2368, 1614, 1544, 1408, 1388, 1347, 1315, 1168,
981, 815, 575, 560. UV-vis (CH3CN): λmax 297, 317, 406 nm.
diol was determined by chiral GC analysis of the correspond-
ing dimethyl acetal (column chiraldex B-PM, 110 °C isother-
mal, tmaj = 15.32 min, tmin = 15.84 min).
HKR of 2-phenyl oxirane catalyzed by the dual-catalyst
systems
THF (35 μL) and water (35 μL, 1.92 mmol) were added to a
solution of the salen CoIII complexes (0.024 mmol) and the
additives (0.024 mmol) in 2-phenyl oxirane (400 μl, 3.5 mmol)
and chlorobenzene (55 mg, 0.48 mmol) dropwise at 0 °C under
continuous stirring. The resulting solution was stirred at 0 °C
for 72 h before addition of THF (5 mL) and subsequent filtra-
tion on silica gel. The yield of resoluted epoxide was determined
by achiral GC analysis (column VF-1ms) with chlorobenzene
as an internal standard. The ee of resoluted epoxide was
determined by chiral GC analysis (column chiraldex B-PM,
110 °C, 10 min, 10 °C min−1 until 170 °C, tmaj = 7.46 min,
tmin = 7.33 min), and the ee of diol was determined by the same
analysis (column chiraldex B-PM, 110 °C, 10 min, 10 °C min−1
until 170 °C, tmaj = 21.69 min, tmin = 21.83 min).
Dynamic HKR of epibromohydrin catalyzed by the
dual-catalyst systems
THF (145 μL) and water (33 μL, 1.81 mmol) were added to a
solution of salen CoIII complexes (0.024 mmol) and the addi-
tives (0.024 mmol) in epibromohydrin (104 μL, 1.21 mmol)
dropwise at 0 °C under continuous stirring. The resulting solu-
tion was stirred at 4 °C for 48 h before the addition of DCM
(5.4 mL), Amberlyst 15 (16 mg) and 2,2-dimethoxypropane
(317 μL, 2.42 mmol). The mixture was stirred at room temper-
ature for another 18 h and then filtered on celite before
removal of the solvents under reduced pressure. The obtained
residue was finally purified by chromatography on silica gel
(pentane/diethyl ether = 95/5) to yield the product as a clear
(light yellow) liquid. The ee of the resulted acetal was deter-
mined by chiral GC analysis (column chiraldex β-PM, 110 °C,
isothermal, tmaj = 5.97 min, tmin = 6.12 min).
Hydrolysis of cyclohexene oxide catalyzed by the
dual-catalyst systems
Water (43 μL, 2.37 mmol) was added to a solution of the salen
CoIII complexes (0.024 mmol) and the additives (0.024 mmol)
in cyclohexene oxide (200 μl, 1.98 mmol) and chlorobenzene
(50 μL) dropwise at 0 °C under continuous stirring. The resulting
solution was stirred at room temperature for 64 hours before
addition of THF (5 mL) and subsequent filtration on silica
gel. The yield of resoluted epoxide was determined by achiral
GC analysis (column VF-1ms) with chlorobenzene as an inter-
nal standard. The ee of the diol was determined by chiral
HKR of 2-phenoxy-methyl-oxirane catalyzed by the
dual-catalyst systems
Salen CoIII complexes (0.024 mmol) and the additives
(0.024 mmol) were dissolved in a mixture of 2-phenoxy-methyl-
oxirane (655 μl, 4.84 mmol) and chlorobenzene (55 mg,
0.48 mmol), to which water (48 μL, 2.66 mmol) was added
dropwise at 0 °C under continuous stirring. The resulting solu-
tion was stirred at 0 °C for 16 h before addition of THF (5 mL)
and subsequent filtration on silica gel. The conversion of epox-
ide was determined by achiral GC analysis (column VF-1ms)
with chlorobenzene as an internal standard. The ee of the epox-
ide was determined by chiral HPLC analysis (column chiralcel
OD–H, hexane/iPrOH = 95/5, 1.0 mL min−1, 25 °C, tmaj = 9.08 min,
tmin = 15.20 min). The ee of the diol was determined by chiral
HPLC analysis (column chiralcel OD-H, hexane/EtOH = 90/10,
0.9 mL min−1, 20 °C, 260 nm, tmaj = 11.07 min, tmin = 18.20 min).
GC analysis (column chiraldex B-PM, 130 °C, 30 min, tmaj
11.18 min, tmin = 10.83 min).
=
Acknowledgements
The CNRS, the Ministère de l'Enseignement Supérieur et de
la Recherche and the “Groupement de Recherche Synthèse et
Procédés Durables pour une Chimie éco-Compatible” du CNRS
are acknowledged for financial support. The authors are also
thankful to the LabEx CharM3At for support. Dr. Martial Toffano
is sincerely thanked for helpful discussion.
HKR of 2-allyloxymethyl-oxirane catalyzed by the
dual-catalyst systems
Water (48 μL, 2.66 mmol) was added to a solution of the salen
CoIII complexes (0.024 mmol) and the additives (0.024 mmol)
in 2-allyloxymethyl-oxirane (574 μl, 4.84 mmol) and chloro-
benzene (55 mg, 0.48 mmol) dropwise at 0 °C under continu-
ous stirring. The resulting solution was stirred at 0 °C for 16 h
before addition of THF (5 mL) and subsequent filtration on
silica gel. The yield of resoluted epoxide was determined by
achiral GC analysis (column VF-1ms) with chlorobenzene as
an internal standard. The ee of resoluted epoxide was deter-
mined by chiral GC analysis (column chiraldex B-PM, 35 °C
isothermal, tmaj = 41.50 min, tmin = 40.21 min). The ee of the
Notes and references
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have been prepared from Cr, Ti and V precursors. Used also as
additives with (S,S)-2-CoIII-OAc in the HKR of epibromohydrin,
none of them showed a significant “match” effect compared to
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