Cerium-based M4L4 tetrahedrons containing hydrogen bond groups as functional molecular flasks for selective reaction prompting

Article abstract of DOI:10.1039/c4nj00062e

The application of metal-organic polyhedrons as "molecular flasks" has resulted in a surge of interest in the reactivity and properties of molecules within their well-defined cavity. Inspired by the structures of the natural enzymatic pockets, two neutral metal-organic tetrahedrons, Ce-TBMN and Ce-TBAS, were achieved via self-assembly by incorporating triamine-triazine and amide groups as hydrogen bond sites into the fragments of the ligands respectively. Both of them could act as molecular flasks to prompt the Knoevenagel condensation reactions of salicylaldehyde derivatives and cyanosilylation reactions of aromatic aldehydes. Experiments of catalysts with different cavity radii and substrates with different sizes and shapes, as well as competitive experiments using nonreactive guests as inhibitors demonstrated that the tetrahedrons exhibited enzymatically catalytic behavior and the catalytic reactions occurred in the "molecular flasks". Control experiments with the H₆TMBN or H ₆TBAS ligands themselves as the catalyst in the Knoevenagel condensation were carried out under the same conditions. For the smaller substrates, their conversions catalyzed by the ligands were significantly lower than those catalyzed by Ce-TBMN or Ce-TBAS, respectively, suggesting that metal-organic polyhedrons could effectively fix multi hydrogen bond groups to avoid the "self-quenching" effect, enhancing the catalytic activity of the multi-hydrogen bond groups in the homogeneous state. the Partner Organisations 2014.

Full text of DOI:10.1039/c4nj00062e

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Cerium-based M4L4 tetrahedrons containing
hydrogen bond groups as functional molecular
flasks for selective reaction prompting†
Cite this: New J. Chem., 2014,
38, 3137
Jing Zhang, Hao Yu, Caixia Zhang, Cheng He* and Chunying Duan
The application of metal–organic polyhedrons as ‘‘molecular flasks’’ has resulted in a surge of interest in
the reactivity and properties of molecules within their well-defined cavity. Inspired by the structures of
the natural enzymatic pockets, two neutral metal–organic tetrahedrons, Ce-TBMN and Ce-TBAS, were
achieved via self-assembly by incorporating triamine-triazine and amide groups as hydrogen bond sites
into the fragments of the ligands respectively. Both of them could act as molecular flasks to prompt the
Knoevenagel condensation reactions of salicylaldehyde derivatives and cyanosilylation reactions of
aromatic aldehydes. Experiments of catalysts with different cavity radii and substrates with different sizes
and shapes, as well as competitive experiments using nonreactive guests as inhibitors demonstrated that
the tetrahedrons exhibited enzymatically catalytic behavior and the catalytic reactions occurred in the
‘‘molecular flasks’’. Control experiments with the H6TMBN or H6TBAS ligands themselves as the catalyst in
the Knoevenagel condensation were carried out under the same conditions. For the smaller substrates,
their conversions catalyzed by the ligands were significantly lower than those catalyzed by Ce-TBMN or
Ce-TBAS, respectively, suggesting that metal–organic polyhedrons could effectively fix multi hydrogen
bond groups to avoid the ‘‘self-quenching’’ effect, enhancing the catalytic activity of the multi-hydrogen
bond groups in the homogeneous state.
Received (in Victoria, Australia)
13th January 2014,
Accepted 25th March 2014
DOI: 10.1039/c4nj00062e
www.rsc.org/njc
On the other hand, homogeneous hydrogen bond-donating
catalysis has emerged as a biomimetic alternative to Lewis acid
Introduction
Metal–organic polyhedrons (MOPs), discrete molecular archi- activation in excellent yield and selectivity.8,9 However, the com-
tectures constructed through the coordination of metal ions petency of H-bond donors presenting in these catalysts was
and organic linkers, have attracted considerable attention due often significantly attenuated as a result of ‘‘self-quenching’’
to their high symmetry, stability and rich chemical/physical through the hydrogen bonding of catalyst molecules to each
properties.1,2 Driven by the ultimate goal of enzyme mimetics, other.10 Consequently, if these catalytically active sites were
their applications in the reactivity modulation of bound guests, incorporated into a defined environment with a larger cavity,
molecular recognition and catalysis are rife with allusions and the self-quenching might be avoided.11
direct comparisons to natural enzymes.3,4 The MOPs have shown
We have reported the assembly of Werner-type capsules con-
excellent advantages in the rational building of microenvironments taining amide groups as multiple hydrogen bonding trigger sites
isolated from bulk solution, with size and shape-selective recogni- for the selective recognition of biomolecules.12 The incorporation
tion of the substrate.5 Although the constructing strategy of MOPs of amide groups as guest-accessible sites within the metal–organic
with controllable configurations has been well established,6 a few cages is a powerful approach to achieve functional flasks for
‘‘artificial enzymes’’ have achieved the levels of catalysis of natural prompting several important reactions, because the amide group
enzymes. The challenge in this field remains the introduction possesses two types of hydrogen bonding sites13 and can act as a
of more kinds of guest-accessible sites into the well-defined base-type catalytic driving force.14 However, in the homogeneous
cavity of the molecular flasks to expand their application in state, simple molecule catalysts containing amide groups may not
molecular recognition and catalysis.7
show excellent catalytic behavior due to the self-quenching effect.15
We reasoned that fixing multi-hydrogen bonding catalytic groups
into MOPs containing inner cavities with rigid conformation
might lead to a new class of materials with significant potential.
To enrich the hydrogen bonding catalytic activity of the
MOPs, through the construction strategy we have established,
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian,
116012, China. E-mail: hecheng@dlut.edu.cn
† CCDC 973898 and 973899. For crystallographic data in CIF or other electronic
format see DOI: 10.1039/c4nj00062e
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here we introduced a functional group, triamine-triazine (melamine),
which has showed interesting multi-hydrogen bonding
formation properties16 in Ce-based molecular tetrahedron
Ce-TBMN-containing amide groups. Additionally, the catalytic
behavior of the Ce-TBAS molecular tetrahedron containing two
types of amide groups with different sizes was also investigated.
The catalytic behavior of the two molecular tetrahedrons
containing many hydrogen bonded groups was examined with
several aldehyde substrates of various sizes and shapes. The
tetrahedrons showed interesting enzymatically catalytic behavior
in the chemical transformations of the Knoevenagel condensation
reaction of salicylaldehyde derivatives and the cyanosilylation
reactions of aromatic aldehydes.
Results and discussion
Structural study of the tetrahedrons
The ligand H6TBMN was easily synthesized through the Schiff
base reaction of 4,40,400-(1,3,5-triazine-2,4,6-triyl)tris(azanediyl)-
tribenzohydrazide and 2-hydroxy-1-naphthaldehyde in ethanol
solution. Mixing the ligand H6TBMN and Ce(NO3)3ꢀ6H2O in
DMF solution gave black solid Ce-TBMN in a yield of 78%.
Single crystal X-ray structural analysis revealed the formation of
a face-driven molecular tetrahedron Ce-TBMN with four cerium
ions on the vertex and the four ligands on the face (Scheme 1).
The compound was crystallized in the C2 space group. The
tetrahedral cage exhibited a 2-fold axial symmetry with two
cerium ions and two ligands presented in an unsymmetrical
unit. Each cerium was nine-coordinated to three ligands as
Scheme 1 Structures of the M4L4 tetrahedrons Ce-TBMN, Ce-TBAS and
Ce-TBBS, as well as their constitutive/constructional fragments. The cerium,
found in the similar Ce-based polyhedron.17 The average Ce–O nitrogen, oxygen and carbon atoms are represented by green, blue, red and
grey, respectively. Hydrogen atoms and solvent molecules are omitted for
(amide), Ce–N (amide) and Ce–O (phenyl) distances were 2.42,
clarity. Average bond distances (Å): Ce-TBMN: Ce–O (amide) 2.42, Ce–N
(amide) 2.62 and Ce–O (phenyl) 2.21; Ce-TBAS: Ce–O (amide) 2.40, Ce–N
(amide) 2.66 and Ce–O (phenyl) 2.20; Ce-TBBS: Ce–O (amide) 2.42,
Ce–N (amide) 2.70 and Ce–O (phenyl) 2.20.
2.62 and 2.21 Å respectively, within the normal ranges reported
in the literature.18 The edge Ceꢀ ꢀ ꢀCe separations were about
18.0 Å and the inner volume of the tetrahedron was 630 Å3 with
the opening size of the windows on the edge being about 18.0 ꢁ
7.6 Å2, allowing the substrate molecules of suitable size to
ingress and egress through the opening to interact with the charged species [(Ce-TBMNꢂ5H)+K]4ꢂ and [(Ce-TBMNꢂ4H)+K]3ꢂ
,
active sites of the tetrahedron. Each triamine–triazine moiety demonstrating that the compound Ce-TBMN is substantially
was sited on the centre of each face, with three NH groups stable in solution.
being fixed in a C3 symmetrical configuration. In total, 12 NH
The tetrahedron cage Ce-TBAS was synthesized according to
groups and 12 coordinated amide groups in the tetrahedron the literature method.17a The structure of Ce-TBAS is similar
cage could act as hydrogen bond active sites. The complementary to that of Ce-TBMN. For Ce-TBAS, the four triamine–triazine
hydrogen bonding and the potential stacking interaction, in moieties were displaced by four 1,3,5-triamide benzene
cooperation with the spatial effects of the tetrahedron nanocage, moieties. The Ceꢀ ꢀ ꢀCe separation of the tetrahedron is ca.
will benefit the enzymatically catalytic behavior to specific reac- 21.0 Å, and the inner volume is about 1000 Å3, with the opening
tions. One DMF solvent molecule was encapsulated in the cage size is about 21.0 ꢁ 11.1 Å2, which are all larger than those of
and several DMF solvent molecules were found outside of the Ce-TBMN. In total, 12 uncoordinated and 12 coordinated
cage, while neither the triamine–triazine groups nor the amide amide groups sited on the faces of the tetrahedron also did
groups were found to form any hydrogen bonds with each other not form any hydrogen bonds with the solvent molecule or with
or with the solvent molecules. It could be anticipated that these each other. The different kinds of amide groups ensure the
groups could act as guest-binding sites to activate corresponding ability of the tetrahedron to be applied in various catalytic
substrates. The electrospray ionization mass spectrometry applications. The ESI-MS of Ce-TBAS exhibited an intense peak
(ESI-MS) data of Ce-TBMN (DMF solution) in the presence of at m/z = 1057.41 which is assigned to the [Ce-TBASꢂ4H]4ꢂ
KOH exhibited an intense peak at m/z 1136.46 and a moderate species, revealing the stability of the M4L4 tetrahedron in
peak at m/z 1515.59, which can be assigned to the negative the solution.
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Table 1 Crystallographic data of compounds Ce-TBMN, Ce-TBAS and Ce-TBBS
Ce-TBMN
Ce-TBASa
Ce-TBBS
Formula
Ce4(C228H156N48O24)ꢀ9C3H7NOꢀ
Ce4(C51H35N9O9)4ꢀ8C3H7NOꢀ
Ce4(C144H100N24O24)ꢀ9C3H7NOꢀ
CH3OHꢀ8H2O
5346.52
200(2)
9CH3OHꢀ7H2O
5231.26
200(2)
CH3OHꢀ2H2O
3836.90
200(2)
Formula weight
T/K
Crystal system
Space group
a/Å
b/Å
c/Å
Monoclinic
C2
Orthorhombic
Fddd
Monoclinic
C2/c
42.6162(16)
23.0136(9)
21.8331(8)
117.460(2)
19000.3(12)
2
18.303(4)
46.917(11)
91.25(2)
—
78 360(32)
8
29.074(4)
22.851(3)
33.440(6)
112.605(2)
20 510(5)
4
b (1)
V/Å3
Z
Dc/g cmꢂ1
0.935
0.526
0.887
0.511
1.243
0.942
m/mmꢂ1
F (000)
5484
0.595(13)
50 323
29 828
0.0893
0.0694
0.1610
1.024
973898
21 504
—
62 007
12 729
0.1247
0.0959
0.2497
0.953
7816
—
49 704
18 005
0.0632
0.0593
0.1832
1.044
Flack parameter
No. ref. measured
No. unique ref.
Rint
R1[I 4 2s(I)]
wR2 (all data)
Goodness of fit
CCDC ref.
987459
973899
R1 = SJFo7 ꢂ 7FcJ/S7Fo7. wR2 = [Sw(Fo ꢂ Fc ) /S(Fo)2]1/2
.
The crystal data of Ce-TBAS has been reported previously,17a the CCDC ref. code is 987459.
2
2 2
a
The Ce-based tetrahedron analogue Ce-TBBS was obtained
by mixing a smaller ligand H6TBBS and Ce(NO3)3ꢀ6H2O in DMF
solution with a yield of 53%. Compared to the former two
ligands, there is only one benzene group inserted into one of
the three arms of the central benzene ring of ligand H6TBBS.
The compound was crystallized in the C2/c space group. In the
molecular tetrahedron of Ce-TBBS, the Ceꢀ ꢀ ꢀCe distance in the
long edges was 13.5 Å and in the short edges was 11.4 Å, and
the inner volume and the opening size of the tetrahedron were
quite a bit smaller than the two cages mentioned above. The
crystallographic data of each compound were listed in Table 1.
The ESI-MS of Ce-TBAS also revealed its stability in DMF
solution with the intense peak at m/z = 1034.22 assigned to
the [Ce-TBBSꢂ3H]3ꢂ species.
Catalytic study of Knoevenagel condensation
The triamine–triazine moieties of Ce-TBMN and free amide
groups of Ce-TBAS could act as basic catalysis sites to promote
the Knoevenagel condensation reaction that requires the for-
mation of an active methylene anion under weak base-catalyzed
conditions.19 Firstly, the recognition of Ce-TBMN to the various
salicylaldehyde substrates was investigated. As shown in Fig. 1
(above), the emission intensity of Ce-TBMN exhibited about a
25-times enhancement when o-Vanillin (5 ꢁ 10ꢂ4 M) was added
into the solution. The Hill-plot profile20 of the fluorescence
titration curves at 478 nm demonstrated the 1 : 1 stoichiometric
host–guest complexation behavior, with the association con-
stant (log Kass) calculated as 4.08 ꢃ 0.06. The addition of other
Fig. 1 Top: spectra of compound Ce-TBMN (5 ꢁ 10ꢂ6 M) in DMF solution
upon the addition of a standard solution of o-Vanillin. The inset exhibits the
responses of Ce-TBMN to other aldehydes for the Knoevenagel conden-
sation. The samples were excited at 385 nm and the emission intensities
were recorded at 478 nm. Bottom: time dependence of the integral area
(IA) ratio variations of the reaction of o-Vanillin catalyzed by Ce-TBMN
based on 1H NMR detection in DMF–CDCl3. IAP and IAR represent the NMR
integral areas at 4.32 ppm and 9.83 ppm respectively.
aldehydes (4-benzoxyl-salicylaldehyde (BOS) or 4-N,N0-dimethyl- solution stirred at room temperature, the o-Vanillin almost
salicylaldehyde (NMS), listed in Table 2) gave association completely reacted after 3 hours. As shown in Table 2, under the
constants (log Kass) of 3.51 and 3.44 respectively.
same conditions, when the size of the salicylaldehyde derivatives
Under the conditions of Ce-TBMN (2 mol%), o-Vanillin (0.08 M) increased, the relative conversion of the Knoevenagel condensa-
and cyanoacetonitrile (0.20 M) in 2 mL DMF–benzene (v/v = 1 : 99) tion of malononitrile decreased significantly. The conversions of
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Table 2 Results for the Knoevenagel condensation reaction catalyzed by various catalysts
Conversion (%)
Ce-TBMN
Ce-TBMN + Ga
H6TBMN
Ce-TBAS
495
Ce-TBAS + Sucb
H6TBAS
Entry
1
Substrates
495
55
28
39
31
13
10
24
2
3
4
43
15
13
24
11
9.4
26
22
20
54
17
14
19
18
15
5
6
25
19
15
13
26
25
34
27
18
16
23
20
Reaction conditions: cyanoacetonitrile (0.20 M), aldehyde (0.08 M), M4L4 tetrahedron (1.6 mM)/ligand(6.4 mM) at room temperature under N2 for
3 hours in 2 mL DMF–benzene (v/v = 1 : 99) solution. a The value is the related conversion of the respective reaction in the presence of guanosine
b
(0.16 M) as the inhibitor. The value is the related conversion of the respective reaction in the presence of sucrose (0.16 M) as the inhibitor.
ethyl cyanoacetate and diethyl malonate with o-Vanillin were displayed through a normal homogeneous system, the inhibi-
about 25% and 19%, respectively. Despite there being many tion of the catalytic reaction was displayed through the addition
factors influencing the conversion of the reactions, the size- of a nonreactive species. In this case, the biomolecule guanosine
selective catalytic properties as well as the same sequence of the with the associate constant (logKass) of 5.78 was chosen as the
reactivity and the response efficiency partly demonstrated that inhibitor for this enzymatic system. As expected, in the presence
the recognition process seems to be an important step for these of 0.16 M of guanosine, the catalytic action by Ce-TBMN
reactions.
decreased significantly. These results gave further proof that
The special microenvironment of the tetrahedron nanocage Ce-TBMN is an interesting molecular flask, within which the
will benefit the enzymatically catalytic behavior. The reactions salicylaldehyde substrates were activated.
were monitored by a 1H NMR tracing process. The product
The size-selective effect of the Knoevenagel condensation
formation was pseudo-zeroth-order with the rate constant being reaction was also exhibited by Ce-TBAS. The association constants
0.6 M hꢂ1 (bottom of Fig. 1, black line), in the case of the (log Kass) of the salicylaldehyde derivatives calculated by fluores-
reaction of o-Vanillin with high concentration (0.40 M). With the cence titration were 4.77, 3.59 and 3.45 for o-Vanillin, BOS and NMS
concentration decreased to 0.04 M, the dependence of the rate respectively. Under the same conditions as Ce-TBMN, o-Vanillin
on the substrate concentration tended to the first order (bottom and cyanoacetonitrile almost completely reacted in 3 hours. As
of Fig. 1, green line), and the combined kinetic data followed the shown in Table 2, the conversion of the larger salicylaldehyde
overall rate law: kinetic rate = k2[guestCCe-TBMN]. The kinetic derivatives with malononitrile catalyzed by Ce-TBAS also decreased
rate of reaction depends on the concentration of the host–guest significantly. The conversion of the corresponding entries were
complexation species rather than the total concentration of the higher than those catalyzed by Ce-TBMN, suggesting the better size-
substrate, suggesting that the substrate and ‘‘enzyme’’ partici- suitability of Ce-TBAS with larger windows and inner space for the
pated in a reversible equilibrium with an enzyme/complex.21 The larger substrates. In addition, the conversion of 4-(benzyloxy)-
catalysis behavior is described in the Michaelis–Menten mecha- salicylaldehyde in the two cases are both low, indicating that
nism in which substrate binding is the first equilibrium prior to the size of this substrate excesses the encapsulation ability of
the rate-limiting step of the reaction.22
both two cages. The inhibition experiments of the related
Although it could not be proved conclusively that the reactions in Ce-TBAS were also carried out by using sucrose,
catalyzed reactions were displayed within the cavities of the which was found to be well encapsulated by Ce-TBAS in our
tetrahedron Ce-TBMN, the size-selective catalytic properties previous study,17a as the inhibitor. In the presence of 0.16 M
and the kinetic study of the catalytic reactions all supported sucrose, the catalytic action of Ce-TBAS decreased significantly.
this hypothesis. To further validate whether the catalytic beha-
Control experiments with the ligands H6TMBN or H6TBAS them-
vior either occurred within the cavity of Ce-TBMN or was just selves as the catalyst were carried out under the same conditions.
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For the small substrates o-Vanillin and 1-hydroxyl-2-napthyl- complexation behavior, with the association constant (log Kass
)
aldehyde, the conversions were significantly lower than those calculated as 4.17 ꢃ 0.24. The addition of other aldehydes
catalyzed by Ce-TBMN and Ce-TBAS respectively. The results (3-NBA and 4-NBA) led to a 1.35 or 1.33 times fluorescence
suggest that for the free ligand, their triamine–triazine and enhancement of the solution, with the association constants
amide groups might form intermolecular hydrogen bonding (log Kass) calculated as 3.95 and 3.68, respectively. Compared
among themselves, deceasing their catalytic efficiency, and the with the Ce-based tetrahedron Ce-TTS which exhibited a lumines-
fixation of these multi-hydrogen bond moieties into the rigid cence decrease towards the corresponding aldehydes due to the
MOPs is a promising way to avoid self-quenching in the homo- photoinduced electron transfer from its triphenylamine moiety to
geneous state. Meanwhile, for the other substrates with larger the guest molecules,13b the different luminescence enhancement
size, the conversions were a little higher than those catalyzed by recognition occurring for Ce-TBMN should be attributed to the
the tetrahedron cage. In all the cases, there was no significant formation of hydrogen bonding between the guests and the NH
difference in the conversion between each entry, also supporting groups, which blocks the PET process from the NH groups to the
that the reaction occurred within the cavity of the tetrahedron. naphthyl moieties in Ce-TBMN. The strongest association con-
We also checked that no reaction occurred with Ce(NO3)2ꢀ6H2O stant for 2-NBA might be due to the formation of multi-hydrogen
as the catalyst.
bonds between the o-position nitrobenzaldehyde and the NH
donor. The recognition between the Ce-TBAS and the other
nitrobenzaldehyde substrates was also investigated. The associa-
tion constants (log Kass) of 2-, 3-, and 4-NBA calculated by fluores-
cence titration were 3.99, 4.13 and 4.36 respectively. The different
recognition sequence compared with that of Ce-TBMN might be
due to the free amide groups being sited in a more steric
hindrance microenvironment in the cavity of Ce-TBAS, and hence
were more difficult to interact with o- and m-nitrobenzaldehyde to
form the hydrogen bond.
Under the conditions of Ce-TBMN (2 mol%), 2-nitrobenz-
aldehyde (0.08 M) and (CH3)3SiCN (0.20 M) in 2 mL DMF–
CHCl3 (v/v = 1 : 99) solution stirred at room temperature, the
2-nitrobenzaldehyde almost completely reacted after 1 hour.
Also, the loading of 2 mol% Ce-TBMN led to more than 80%
conversion for various nitrobenzaldehydes. The substrate
1-naphthyl-aldehyde and 4-hydroxy-1-naphthaldehyde with larger
size gave lower conversions of about 63% and 38% respectively
under the same conditions. The product formation was pseudo-
zeroth-order with the rate constant being 2.4 M hꢂ1 (bottom of
Fig. 2, black line), in the case of the reaction of 2-NBA with high
concentration (0.40 M). With the concentration decreased to
0.04 M, the dependence of the rate on the substrate concen-
tration tended to be first-order. Similarly, in the presence of
0.16 M of guanosine, the catalytic action of Ce-TBMN decreased
significantly. The competitive inhibition behavior suggested
that the catalytic action also occurred within the cavity of
Ce-TBMN.
Catalytic study of the cyanosilylation reaction
The similar Ce-based tetrahedron reported previously in our
group has shown good activity in promoting the cyanosilylation
reaction,23 a convenient route to cyanohydrins which are key
derivatives in the synthesis of fine chemicals and pharma-
ceuticals.24 The recognition between Ce-TBMN and the various
nitrobenzaldehyde substrates for the cyanosilylation was inves-
tigated. As shown in Fig. 2 (top), the emission intensity of
Ce-TBMN exhibited about a 1.7 times enhancement when
2-nitrobenzaldehyde (2-NBA, 2 ꢁ 10ꢂ4 M) was added into the
solution. The Hill-plot profile of the fluorescence titration curves
at 478 nm demonstrated the 1 : 1 stoichiometric host–guest
For the related cyanosilylations catalyzed by Ce-TBAS, as
shown in Table 3, under the same reaction conditions as
Ce-TBMN, the conversion of the various nitrobenzaldehydes
was also high after 1 hour, but the sequence is different. In this
case, the conversion rate of 2-NBA is lower than that of 3- and
4-NBA. The different sequence of the conversion rate in the
related entries compared with those in the case of Ce-TBMN, as
well as the same sequence of the reactivity and the response
Fig. 2 Top: the luminescence response of compound Ce-TBMN (red
column) and Ce-TBAS (blue column) in DMF solution upon the addition of a efficiency in both of the two systems, suggested that substrate
standard solution of various nitrobenzaldehydes. The samples were excited
binding is the first step in these catalytic reactions. The con-
version rate of 1-naphthyl-aldehyde was about 65%, which was
similar to that catalyzed by Ce-TBMN. Meanwhile, the conver-
sion rate of 4-hydroxy-1-naphthaldehyde was 50%, higher than
that by Ce-TBMN, suggesting the better size-suitability of the
at 385 nm and the emission intensities were recorded at 478 nm. Bottom:
time dependence of the integral area (IA) ratio variations of the reaction of
2-nitrobenzaldehyde catalyzed by Ce-TBMN, based on 1H NMR detection
in DMF–CDCl3. IAP and IAR represent the NMR integral areas at 6.22 ppm
and 10.42 ppm, respectively.
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Table 3 Results of the cyanosilylation reaction catalyzed by various catalysts
Conversion (%)
Ce-TBMN (log Kass
)
Ce-TBMN + Ga
Ce-TBAS (log Kass)
89 (3.99 ꢃ 0.22)
Ce-TBAS + Sucb
Ce-TBBS
Entry
1
Substrates
4 97 (4.17 ꢃ 0.24)
497 (3.95 ꢃ 0.16)
66
53
72
2
3
63
54
4 97 (4.13 ꢃ 0.18)
4 97 (4.36 ꢃ 0.19)
59
57
67
74
89 (3.68 ꢃ 0.17)
4
5
63
38
28
18
65
50
31
22
52
31
Reaction conditions: (CH3)3SiCN (0.20 M), aldehyde (0.08 M), M4L4 tetrahedron (1.6 mM) at room temperature under N2 for 1 hour in 2 mL
a
DMF–CHCl3 (v/v = 1 : 99) solution. The value is the related conversion of the respective reaction in the presence of guanosine (0.16 M) as the
b
inhibitor. The value is the related conversion of the respective reaction in the presence of sucrose (0.16 M) as the inhibitor.
larger cavity of Ce-TBAS towards the larger substrate. Additionally, the ‘‘self-quenching’’ between themselves, enhancing their cata-
in the presence of 0.16 M sucrose, the cyanosilylation catalytic lytic ability in the homogeneous state.
action of the Ce-TBAS system decreased significantly.
To further validate the size and shape-selectivity of the
MOPs, the related catalytic actions by the reference tetrahedron
Ce-TBBS were investigated. Compared with the Ce-TBMN and
Experimental
Materials
Ce-TBAS, Ce-TBBS has a smaller inner cavity and opening size,
and no free hydrogen bond sites on the face. Under the same
conditions, the loading of 2 mol% Ce-TBBS led to no more than
an 80% conversion rate for the nitrobenzaldehydes. In this case,
the 3-NBA gave the lowest conversion rate among the three
nitrobenzaldehydes, possibly due to the m-position nitrobenz-
aldehyde being more difficult to pass through the small window
of the Ce-TBBS (approximate two dimensional sizes calculated
from Chem 3D: 2-NBA, 4.46 Å ꢁ 4.72 Å; 3-NBA 6.50 Å ꢁ 5.17 Å;
4-NBA, 6.67 Å ꢁ 4.32 Å). All of the experimental results strongly
suggest that the catalytic reactions occurred within the inner
cavities of the tetrahedral cages.
All chemicals were of reagent grade quality, obtained from
commercial sources and used without further purification.
The elemental analyses of C, H and N were performed on a
Vario EL III elemental analyzer. 1H NMR spectra were measured
on a Bruker 400 M spectrometer. ESI mass spectra were carried
out on a HPLC-Q-TOF MS spectrometer using CH3CN as the
mobile phase.
General spectroscopic methods
Solution fluorescence titration spectra and selectivity experiments
were checked using an EDINBURGH FS920 luminescence spectro-
meter. Stock solutions (1.0 ꢁ 10ꢂ2 M) of the substrate were
prepared. High concentrations of the stock solutions of Ce-TBMN
and Ce-TBAS (1.0 mM) were prepared in DMF. Before the spectro-
scopic measurements, the solution was freshly prepared by diluting
Conclusions
In summary, we reported the achievement of Ce-based molecular the high concentration stock solution into the corresponding
tetrahedrons Ce-TBMN and Ce-TBAS containing multi-hydrogen solution. For all the titration experiments, spectra were recorded
bond active sites. The tetrahedrons with different size windows 3 min after adding the substrate to ensure complete equilibrium.
and cavities could work as efficient molecular flasks to selectively The excitation and emission slit widths were modified to adjust the
prompt the Knoevenagel condensation reaction of salicylalde- luminescence intensity to a suitable range. All the spectroscopic
hyde derivatives and cyanosilylation reactions of aromatic alde- measurements were performed at least in triplicate and averaged.
hydes. The catalysts exhibited typical enzymatically catalytic
Trimethyl-4,40,400-(1,3,5-triazine-2,4,6-triyl)tris(azanediyl)tri-
behavior: the reactions took place within the molecular flasks, benzoate25. Cyanuric chloride (0.92 g, 5.0 mmol) was added in
not in a normal homogeneous manner. Additionally, the multi- one portion to a stirred solution of methyl 4-aminobenzoate
hydrogen bond groups could be fixed in the rigid MOPs to avoid (2.5 g, 17 mmol) in 75 mL of glacial acetic acid (AcOH), and the
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mixture was heated (30 min, steam bath (100 1C)). The products 11.29 (s, 1H5), 11.19 (s, 2H12), 8.73 (s, 2H13), 8.71 (s, 1H6), 8.56
precipitated from solution as white solids and were recovered (s, 1H1), 8.52 (s, 2H2), 8.18 (d, J = 8.0 Hz, 2H4), 8.09 (d, J = 8.0 Hz,
by filtration. The solid products were washed with boiling water 2H3), 7.60 (3H7,14), 7.33 (3H9,16), 6.95 (6H7,10,15,17). 13C NMR
(approximately 20 mL ꢁ 3) to neutral pH and dried in vacuum. (400 MHz, DMSO-d6, ppm): d 162.82 (k,s), 162.50 (q,z), 157.98
1
Yield: 2.4 g, 91%. H NMR (400 MHz, DMSO-d6, ppm): d 9.89 (l,t), 149.10 (f,b), 149.00 (j), 142.44 (g), 140.16 (d), 134.59 (e,c),
(s, 3H–NH–), 8.01 (d, J = 8.4 Hz, 6HAr–H), 7.93 (d, J = 8.8 Hz, 6HAr–H), 132.81 (m), 132.03 (v), 131.90 (k,i), 130.02 (l,h), 129.82 (o),
3.85 (s, 9H–CH).
129.64 (x), 128.99 (a), 127.70 (n), 127.41 (w), 119.86 (r), 119.82 (u),
4,40,400-(1,3,5-Triazine-2,4,6-triyl)tris(azanediyl)tribenzohydrazide. 119.22 (p), 119.16 (y).
A mixture solution of 80% hydrazine hydrate (0.15 L) and
Ce-TBBS. A solution of Ce(NO3)3ꢀ6H2O (44 mg, 0.10 mmol),
trimethyl 4,40,400-(1,3,5-triazine-2,4,6-triyl)tris(azanediyl)-tribenzoate ligand H6TBBS (64 mg, 0.10 mmol) and NaOAc (25 mg, 0.30 mmol)
(1.9 g, 3.5 mmol) was stirred for 24 h at boiling temperature. A in DMF (10 mL) was stirred for 2 h at room temperature. Then the
white precipitate was formed, which was collected by filtration, solution was left for two weeks at room temperature to give X-ray-
washed with methanol and dried in vacuum. Yield: 1.6 g, 85%. quality black block crystals. Yield: about 53% (based on the crystals
1H NMR (400 MHz, DMSO-d6, ppm): d 9.64 (s, 3H–NH–N), 9.63 washed with methanol and dried in vacuum). Anal calc. for
(s, 3H–NH–), 7.91 (d, J = 8.0 Hz, 6HAr–H), 7.81 (d, J = 8.4 Hz, 6HAr–H), Ce4C144H100N24O24ꢀ5C3H7NO: H 3.91 C 54.93 N 11.68%. Found:
4.43 (s, 6H–NH).
H 4.12, C 55.36, N 11.20%.
H6TBMN. A mixture solution of 4,40,400-(1,3,5-triazine-2,4,6-
triyl)tris(azanediyl)tribenzohydrazide (0.81 g, 1.5 mmol) and
2-hydroxy-1-naphthaldehyde (0.87 g, 5.0 mmol) in ethanol
(0.10 mL) was stirred for 24 h at boiling temperature. A brown
precipitate was formed, which was collected by filtration, washed
with methanol and dried in vacuum. Yield: 1.3 g, 85%. Anal calc.
for C57H42N12O6ꢀH2O: H 4.40, C 67.85, N 16.66%. Found: H 4.45,
Crystallography
The intensities of Ce-TBMN and Ce-TBBS were collected on a Bruker
SMART APEX CCD diffractometer with graphite monochromated
Mo-Ka radiation (l = 0.71073 Å) using the SMART and SAINT
programs.26 The structures were solved by direct methods and
refined on F2 by full-matrix least-squares methods with SHELXTL
version 5.1.27 The SQUEEZE protocol inside PLATON was used to
remove the void electron density of the two structures. In the
structural refinement of Ce-TBMN, one of the central benzene rings
and the nitrogen atom attached to it were disordered into two parts
with their s.o.f. being refined as free values, and the C–C bond
distance and the diagonal C–C distance in one disordered phenyl
ring were fixed as 1.39 Å and 2.78 Å, respectively. Except for the
disordered parts and partly occupied solvent molecules, the other
non-hydrogen atoms were refined anisotropically. Hydrogen atoms
within the ligand backbones and the solvent DMF molecules were
fixed geometrically at calculated distances and allowed to ride on the
parent non-hydrogen atoms. To assist the stability of the refine-
ments, several restrains were applied: several bond distances in
solvent DMF molecules were restrained as idealized values. Thermal
parameters on adjacent atoms in two of the naphthyl rings were
restrained to be similar. In the structural refinement of Ce-TBBS, all
the non-hydrogen atoms were refined anisotropically. Except for the
solvent methanol and water molecules, hydrogen atoms within
the ligand backbones and solvent DMF molecules were fixed geo-
metrically at calculated distances and allowed to ride on the parent
non-hydrogen atoms. Thermal parameters on adjacent atoms of
several solvent DMF molecules were restrained to be similar.
1
C 67.79, N 16.63%. H NMR (400 MHz, DMSO-d6, ppm): d 12.86
(s, 3H12), 12.14 (s, 3H4), 9.89 (s, 3H1), 9.51 (s, 3H5), 8.22 (d, J =
8.8 Hz, 3H10), 8.11 (d, J = 8.4 Hz, 6H3), 8.03 (d, J = 8.4 Hz, 6H2), 7.94
(d, 6H11), 7.91 (d, m, 6H8),7.61 (t, J = 7.6 Hz, 3H7), 7.42 (t, J =
7.4 Hz, 3H9), 7.25 (d, J = 9.2 Hz, 3H6). 13C NMR (400 MHz, DMSO-d6,
ppm): d 206.95 (d), 164.49 (a), 162.57 (l), 158.40 (o), 146.73 (e),
143.96 (n), 133.04 (g), 132.06 (m), 129.44 (c), 128.85 (i), 128.27 (g),
128.17 (f), 126.19 (p), 123.96 (h), 121.00 (k), 119.84 (b), 119.39 (q).
Ce-TBMN. A solution of Ce(NO3)3ꢀ6H2O (44 mg, 0.10 mmol),
ligand H6TBMN (99 mg, 0.10 mmol) and NaOAc (25 mg,
0.30 mmol) in DMF (10 mL) was stirred for 2 h at room tempera-
ture. Then the solution was left for two weeks at room temperature
to give X-ray-quality black block crystals. Yield: about 78% (based
on the crystals washed with methanol and dried in vacuum). Anal
calc. for Ce4C228H156N48O24ꢀ4C3H7NO: H 3.86, C 59.99, N 15.16%.
Found: H 4.10, C 58.94, N 14.92%.
1,10-Biphenyl-3,40,5-tricarbohydrazide. A mixture solution
of 80% hydrazine hydrate (12 g, 0.18 mmol), trimethyl-1,10-
biphenyl-3,40,5-tricarboxylate (0.98 g, 3.0 mmol) and methanol
(0.10 L) was stirred for 12 h at boiling temperature. A white
precipitate was formed, which was collected by filtration, washed
with methanol and dried in vacuum. Yield: 0.86 g, 88%. 1H NMR
(400 MHz, DMSO-d6, ppm): d 9.98 (s, 2H–NH–N), 9.87 (s, 1H–NH–N),
8.29 (s, 1HAr–H), 8.27 (s, 2HAr–H), 7.98 (d, J = 8.0 Hz, 2HAr–H), 7.92
(d, J = 8.0 Hz, 2HAr–H), 4.59 (s, 6H–NH).
Acknowledgements
H6TBBS. A mixture solution of 1,10-biphenyl-3,40,5-tricarbo-
hydrazide (0.66 g, 2.0 mmol) and 2-hydroxybenz-1-aldehyde
(0.81 g, 6.6 mmol) in methanol (0.10 mL) was stirred for 12 h
at boiling temperature. A white precipitate was formed, which
was collected by filtration, washed with methanol and dried in
vacuum. Yield: 1.2 g, 93%. Anal calc. for C36H28N6O6ꢀ2H2O:
H 4.77, C 63.90, N 12.42%. Found: H 4.71, C 67.82, N 12.45%.
1H NMR (400 MHz, DMSO-d6, ppm): d 12.36 (s, 2H18), 12.24 (s, 1H11),
This work was supported by NSFC 21171029.
Notes and references
1 (a) M. Fujita, M. Tominaga, A. Hori and B. Therrien,
Acc. Chem. Res., 2005, 38, 371; (b) D. Fiedler, D. H. Leung,
R. G. Bergman and K. N. Raymond, Acc. Chem. Res., 2005,
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 3137--3145 | 3143

View Article Online
Paper
38, 351; (c) J.-M. Lehn, Chem. Soc. Rev., 2007, 36, 151;
NJC
R. P. Herrera and A. Riccia, Synlett, 2004, 2374; (e) M. M.
Biddle, M. Lin and K. A. Scheidt, J. Am. Chem. Soc., 2007,
129, 3830; ( f ) O. Lifchits, M. Mahlau, C. M. Reisinger,
A. Lee, C. Fares, I. Polyak, G. Gopakumar, W. Thiel and
B. List, J. Am. Chem. Soc., 2013, 135, 6677.
(d) R. W. Saalfrank, H. Maid and A. Scheurer, Angew. Chem.,
Int. Ed., 2008, 47, 8794; (e) M. D. Ward, Chem. Commun.,
2009, 4487; ( f ) R. Chakrabarty, P. S. Mukherjee and
P. J. Stang, Chem. Rev., 2011, 111, 6810.
¨
2 (a) I. M. Mu¨ller and D. Moller, Angew. Chem., Int. Ed., 2005, 10 (a) L. J. Prins, D. N. Reinhoudt and P. Timmerman, Angew.
44, 2969; (b) S. Hiraoka, K. Harano, M. Shiro, Y. Ozawa,
N. Yasuda, K. Toriumi and M. Shionoya, Angew. Chem., Int.
Ed., 2006, 45, 6488; (c) I. S. Tidmarsh, T. B. Faust, H. Adams,
L. P. Harding, L. Russo, W. Clegg and M. D. Ward, J. Am.
Chem. Soc., 2008, 130, 15167; (d) P. Mal, B. Breiner,
Chem., Int. Ed., 2001, 40, 2382; (b) S. L. Li, T. X. Xiao, C. Lin
and L. Y. Wang, Chem. Soc. Rev., 2012, 41, 5950; (c) M. P.
Beecham, G. J. Clarkson, G. Hall and A. Marsh, ChemPhysChem,
2013, 14, 3909; (d) T. Seki, X. Lin and S. Yagai, Asian J. Org.
Chem., 2013, 2, 708.
K. Rissanen and J. R. Nitschke, Science, 2009, 324, 1697; 11 (a) J. M. Roberts, B. M. Fini, A. A. Sarjeant, O. r. K. Farha,
(e) J.-R. Li and H.-C. Zhou, Nat. Chem., 2010, 2, 893;
( f ) S. Bivaud, J.-Y. Balandier, M. Chas, M. Allain, S. Goeb
and M. Salle, J. Am. Chem. Soc., 2012, 134, 11968.
3 (a) X. Zhang and K. N. Houk, Acc. Chem. Res., 2005, 38, 379;
(b) T. S. Koblenz, J. Wassenaar and J. N. H. Reek, Chem. Soc.
J. T. Hupp and K. A. Scheidt, J. Am. Chem. Soc., 2012,
134, 3334; (b) E. Dugan, Z. Wang, M. Okamura, A. Medina
and S. M. Cohen, Chem. Commun., 2008, 3366; (c) X. W.
Dong, T. Liu, Y. Z. Hu, X. Y. Liu and C.-M. Che, Chem.
Commun., 2013, 49, 7681.
Rev., 2008, 37, 247; (c) J. Rebek Jr, Acc. Chem. Res., 2009, 12 (a) C. He, Z. H. Lin, Z. He, C. Y. Duan, C. H. Xu, Z. M. Wang
42, 1660; (d) M. J. Wiester, P. A. Ulmann and C. A. Mirkin,
Angew. Chem., Int. Ed., 2011, 50, 114.
and C. H. Yan, Angew. Chem., Int. Ed., 2008, 47, 877;
(b) H. M. Wu, C. He, Z. H. Lin, Y. Liu and C. Y. Duan, Inorg.
Chem., 2009, 48, 408; (c) Y. Liu, X. Wu, C. He, R. Zhang and
C. Y. Duan, Dalton Trans., 2008, 5866; (d) Y. Liu, X. Wu,
C. He, Z. Li and C. Y. Duan, Dalton Trans., 2010, 7727;
(e) Y. Liu, X. Wu, C. He, Y. Jiao and C. Y. Duan, Chem.
Commun., 2009, 7554; ( f ) L. Zhao, S. Y. Qu, C. He, R. Zhang
and C. Y. Duan, Chem. Commun., 2011, 9387.
4 (a) Q.-T. He, X.-P. Li, Y. Lu, Z.-Q. Yu, W. Wang and C.-Y. Su,
Angew. Chem., Int. Ed., 2009, 48, 6156; (b) Y. Inokuma,
M. Kawanom and M. Fujita, Nat. Chem., 2011, 3, 149;
(c) Z. J. Wang, K. N. Clary, R. G. Bergman, K. N. Raymond
and F. D. Toste, Nat. Chem., 2013, 5, 100; (d) J. L. Bolliger,
A. M. Belenguer and J. R. Nitschke, Angew. Chem., Int. Ed.,
2013, 52, 7958.
5 (a) M. Yoshizawa, J. K. Klosterman and M. Fujita,
Angew. Chem., Int. Ed., 2009, 48, 3418; (b) M. D. Pluth,
R. G. Bergman and K. N. Raymond, Science, 2007, 316, 85;
(c) M. Yoshizawa, M. Tamura and M. Fujita, Science, 2006,
312, 251.
13 (a) C. M. Lee and W. D. Kumler, J. Am. Chem. Soc., 1962,
84, 571; (b) H. A. Bent, Chem. Rev., 1968, 68, 587; (c) P. L.
Huyskens, J. Am. Chem. Soc., 1977, 99, 2578; (d) C. Nativi,
M. Cacciarini, O. Francesconi, A. Vacca, G. Moneti, A. Ienco
and S. Roelens, J. Am. Chem. Soc., 2007, 129, 4377;
(e) Y. Ferrand, M. P. Crump and A. P. Davis, Science, 2007,
318, 619.
6 (a) D. L. Caulder and K. N. Raymond, Acc. Chem. Res., 1999,
32, 975; (b) S. Leininger, B. Olenyuk and P. J. Stang, Chem. 14 Y. Liu, R. Zhang, C. He, D. B. Dang and C. Y. Duan, Chem.
Rev., 2000, 100, 853; (c) R. M. McKinlay, G. W. V. Cave and Commun., 2010, 746.
J. L. Atwood, Proc. Natl. Acad. Sci. U. S. A., 2005, 102, 5944; 15 S. Hasegawa, S. Horike, R. Matsuda, S. Furukawa,
(d) D. J. Tranchemontagne, Z. Ni, M. O’Keeffe and
O. M. Yaghi, Angew. Chem., Int. Ed., 2008, 47, 5136.
K. Mochizuki, Y. Kinoshita and S. Kitagawa, J. Am. Chem.
Soc., 2007, 129, 2607.
7 (a) L. Cronin, Angew. Chem., Int. Ed., 2006, 45, 3576; 16 (a) D. S. Lawrence, T. Jiang and M. Levett, Chem. Rev., 1995,
(b) C. Schmuck, Angew. Chem., Int. Ed., 2007, 46, 5830;
(c) M. D. Pluth, D. Fiedler, J. S. Mugridge, R. G. Bergman
and K. N. Raymond, Proc. Natl. Acad. Sci. U. S. A., 2009,
95, 2229; (b) F. H. Beijer, R. P. Sijbesma, J. A. J. M.
Vekemans, E. W. Meijer, H. Kooijman and A. L. Spek,
J. Org. Chem., 1996, 61, 6371; (c) Z. L. Jiang, L. P. Zhou
and A. H. Liang, Chem. Commun., 2011, 47, 3162; (d) S. Quici,
A. Manfredi, G. Pozzi, M. Cavazzini and A. Rozzoni, Tetrahedron,
1999, 55, 10487.
`
106, 10438; (d) D. M. Vriezema, M. C. Aragones, J. A. A. W.
Elemans, J. J. L. M. Cornelissen, A. E. Rowan and R. J. M.
Nolte, Chem. Rev., 2005, 105, 1445.
8 (a) P. R. Schreiner, Chem. Soc. Rev., 2003, 32, 289; 17 (a) Y. Jiao, J. Zhang, L. J. Zhang, Z. H. Lin, C. He and
(b) M. S. Taylor and E. N. Jacobsen, Angew. Chem., Int. Ed.,
2006, 45, 1520; (c) E. N. Jacobsen and A. G. Doyle, Chem.
Rev., 2007, 107, 5713; (d) S. J. Connon, Chem. Commun.,
C. Y. Duan, Chem. Commun., 2012, 48, 6022; (b) J. Wang,
C. He, P. Y. Wu, J. Wang and C. Y. Duan, J. Am. Chem. Soc.,
2011, 133, 12402.
2008, 2499; (e) Z. Zhang and P. R. Schreiner, Chem. Soc. Rev., 18 (a) S. Mizukami, H. Houjou, M. Kanesato and K. Hiratani,
2009, 38, 1187; ( f ) B. G. Zhao, Z. B. Han and K. L. Ding,
Angew. Chem., Int. Ed., 2013, 52, 4744.
Chem. – Eur. J., 2003, 9, 1521; (b) M. Gon´zalez-Lorenzo,
C. Platas-Iglesias, F. Avecilla, C. F. G. C. Geraldes, D. Imbert, J.-
´
9 (a) M. S. Sigman and E. N. Jacobsen, J. Am. Chem. Soc., 1998,
120, 4901; (b) P. R. Schreiner and A. Wittkopp, Org. Lett.,
C. G. Bu¨nzli, A. de Blas and T. Rodriguez-Blas, Inorg. Chem.,
2003, 42, 6946.
2002, 4, 217; (c) E. N. Jacobsen and A. G. Wenzel, J. Am. 19 (a) E. Knoevenagel, Chem. Ber., 1894, 27, 2345; (b) G. Marciniak,
Chem. Soc., 2002, 124, 12964; (d) G. Dessole, D. Gabriella, A. Delgado, G. Leelere, J. Velly, N. Decken and J. Schwartz,
3144 | New J. Chem., 2014, 38, 3137--3145
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
J. Med. Chem., 1989, 32, 1402; (c) L. Rand, J. V. Swisher and 23 Y. Jiao, J. Wang, P. Y. Wu, L. Zhao, C. He, J. Zhang and
C. J. Cronix, J. Org. Chem., 1962, 27, 3505. C. Y. Duan, Chem. – Eur. J., 2014, 20, 2224–2231.
20 (a) K. A. Connors, Binding Constants, John Wiley, New York, 24 (a) K. Higuchi, M. Onaka and Y. Izumi, Bull. Chem. Soc. Jpn.,
1987; (b) P. S. Corbin, PhD Dissertation, University of
Illinois at Urbana-Champaign, Urbana, IL, 1999.
21 (a) C. J. Hastings, D. Fiedler, R. G. Bergman and K. N.
1993, 66, 2016–2032; (b) R. J. H. Gregory, Chem. Rev., 1999,
99, 3649; (c) M. North, Tetrahedron: Asymmetry, 2003,
14, 147.
Raymond, J. Am. Chem. Soc., 2008, 130, 10977; (b) D. Fiedler, 25 A. K. Kirill, J. Heterocycl. Chem., 2008, 45, 533.
H. van Halbeek, R. G. Bergman and K. N. Raymond, J. Am. 26 SMART and SAINT, Area Detector Control and Integration
Chem. Soc., 2006, 128, 10240.
Software, Siemens Analytical X-ray Systems, Inc., Madison,
22 (a) T. McKee and J. R. McKee, Biochemistry: The Molecular
WI, 1996.
Basis of Life, McGraw-Hill, New York, 3rd edn, 2003; 27 G. M. Sheldrick, SHELXTL V5.1, Software Reference Manual,
(b) R. Breslow, Acc. Chem. Res., 1991, 24, 159. Bruker, AXS, Inc., Madison, WI, 1997.
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 3137--3145 | 3145