Synthesis, characterization, and properties of a benzofuran-based cage-shaped borate: Photo activation of Lewis acid catalysts

Article abstract of DOI:10.1039/c6cc00291a

A cage-shaped borate with benzofuran moieties was synthesized. This borate showed a higher degree of catalytic activity for Mukaiyama-aldol type reactions than a simple benzene-based cage-shaped borate induced by self-aggregation. Moreover, the exposure of the complex to black-light irradiation enhanced the catalytic activity.

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Synthesis, Characterization, and Properties of a
Benzofuran-based Cage-shaped Borate: Photo
Activation of Lewis Acid Catalysts
Cite this: DOI: 10.1039/x0xx00000x
Akihito Konishi,a,b Ryosuke Yasunaga,a Kouji Chibac and Makoto Yasuda*a
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
cage-shaped borate with benzofuran moieties was
synthesized. This borate showed a higher degree of catalytic
activity for Mukaiyama-aldol type reactions than a simple
benzene-based cage-shaped borate induced by self-
aggregation. Moreover, the exposure of the complex to black-
light irradiation enhanced the catalytic activity.
Precise control of Lewis acidity is very important for organic synthesis
because activation of molecules mainly depends on the character of
the Lewis acid.1 The Lewis acidity is often controlled by the steric or
electronic factors of the species. Recently, we developed cage-
shaped borate esters that have a triphenolic ligand with a tripod-
chelated structure such as 2, which shows significantly different
characteristics than those of the planar structure of a common borate
Scheme 1 Chemical structures of planer and cage-shaped triphenolic borates.
We planned to prepare a benzofuran-based triphenolic ligand from a
commercially available 5-methoxybenzofuran
previously reported synthetic route for the simple cage-shaped
borate 2 2a
5-methoxybenzofuran was deprotonated by BuLi and
treated with ethyl chloroformate, giving an undesired regioisomeric
carbinol bound at the 2-position of the methoxybenzofuran. Then,
as a regioselective bromination at the ortho-position of phenols has
been reported,8 5-hydroxybenzofuran
was prepared via the
deprotection of a methoxy group of
by BBr3. The bromination of 78
by NBS/ Pr2NH successfully afforded 4-bromo-5-hydroxybenzofuran
. After the protection of OH into OMe, the addition of BuLi for a
5 (Scheme 2). As our
1
.2 As shown in Scheme 1, a cage-shaped borate
the introduction of substituents, R, such as halogens3 or aryl groups.4
The structure of the cage shape in allows precise control of the
3 can be tuned by
,
5
n
3
dihedral angles of C-O-B-O in the cage and LUMO levels by changing
a tether atom, X, from carbon to silicon.5 These factors lead to Lewis
acids with the same type of template but a variety of characteristics.
A complete replacement of the benzene rings with heteroaromatic
6
7
5
rings or with a partial embedding of heteroatoms in the
-
i
conjugated system has been an attractive way to control either the
physical or chemical properties.6 Thus, the ring-fusion of
heteroaromatic moieties to the aromatic portions in the cage-shaped
borates would cause electronic perturbations in the Lewis acid center
without steric effect, which would allow precise control of the Lewis
acidity. In the present study, heteroaromatic moieties in the form of
benzofuran-frameworks were introduced into the cage structure,
which conferred characteristics that differed from those of the
8
n
halogen-lithium exchange followed by treatment with ethyl
chloroformate gave the desired triarylmethanol 10 selectively bound
at the 4-position of methoxy-4-benzofuran. A reduction of 10 under
acidic conditions in THF/MeCN9 and a deprotection of the methoxy
groups by BBr3 afforded the tris(5-hydrofuranyl)methane 12. A
mixing of 12 with BH3·THF in THF readily generated the cage-shaped
borate
The NMR spectroscopy of
shaped borate; the upfield/downfield shift of the
at the tether position was compared with those of the ligand 12:
4·THF (Scheme 2).
previously synthesized borates
2 and 3. A benzofuran moiety has an
4
·THF showed typical signals for a cage-
(1H)/ (13C) of C-H
intrinsic dipole7 due to the ring oxygen with a polarity that affects the


Lewis acidity of the complex.
(
(1H) 6.69

6.32 ppm,

(13C) 38.9

43.2 ppm)3. The coordinating THF
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showed broad signals at the lower chemical shifts compared with
that of free THF. The recrystallization of ·THF from hexane/CH2Cl2
Table 1. Complexation of boron compounds with carbonyl compound 13.
4
gave a suitable crystal for X-ray analysis. The ORTEP drawings are
shown in Fig. 1.10 The bond length of the B-O(THF) was 1.575(3) Å,
which was shorter than that (1.595(8) Å) of the simple cage-shaped
borate
2
·THF. The sum of the bond angles of O-B-O (O: ligand) was
·THF, while the sum of the bond angles (344.81°) for
·THF was slightly larger. These structural features indicated that
·THF had a slightly higher Lewis acidity than ·THF.
343.96° for
4
2
4
2
Fig.2. Optimum structures and its MO diagram of
4 and 2.
The DFT calculation of
4 at the B3PW91/6-31+G (d,p) level showed it
to be ligand-free, three-coordinated structure, which would
a
contribute to an active Lewis acid species during the reaction course
(Fig. 2 and Table S1 in the Supplementary Information). The dihedral
angles C-O-B-O, which reflect the shape of the cage, were almost the
Scheme 2 Synthesis of benzofuran-based triphenolic ligand 12 and cage-shaped
borate
4.
same as those of the species 2 2a
between the B atom and the benzofuran skeleton in
.
However, an effective conjugation
was estimated,
4
which would lead to a decrease in the energy level of the unoccupied
orbital of a Lewis acid (in this case, next-LUMO level), while the orbital
of
was -21.6 kcal/mol (-0.94 eV) for 4, which was lower than those of the
benzene-based borates (-18.3 kcal/mol) and 3c (-16.8 kcal/mol)
(Table S1)3. Although a lower next-LUMO level of
was expected to
contribute to a large reaction rate, the pyridine-complexation energy,
, reflected a catalytic turnover of (-18.8 kcal/mol) that was similar
to that of (-19.2 kcal/mol). Generally, when a next-LUMO energy
level becomes lower, the stabilization energy shows larger (larger
negative for ), which means that Lewis acidity and catalytic
turnover have a trade-off relationship. It should be noted that the
borate showed an unexpected relationship that resulted in a high
affinity to the substrate and a high catalytic turnover. Significant
differences between and were found in the magnitude of the
2 is located closer to its B atom. The energy level of the next-LUMO
2
4

E
4
2

E
Fig. 1. ORTEP drawing of 4·THF at the 50% probability level (aryl hydrogens are
omitted for clarity) (a) Side view and (b) top view (THF is omitted for clarity).
Selected bond lengths (Å): B-O(1) 1.441(3), B-O(2) 1.435(3), B-O(3) 1.435(3), B-
O(4) 1.575(3). Selected bond angles (deg): O(1)-B-O(2) 114.3(2), O(2)-B-O(3)
114.5(2), O(3)-B-O(1) 115.2(2), O(1)-B-O(4) 104.2(2), O(2)-B-O(4) 103.6(2), O(3)-
B-O(4) 103.1(2).
4
4
2
dipole moment and in the charge distribution (Fig. S1). Both
compounds had a dipole moment that was directed from the cage
Lewis acidity was also estimated via the NMR chemical shift

(13C)
center to the tether position, but the magnitude of the dipole of
4 is
and infrared stretching frequency of the 2,6-dimethyl- -pyrone 13
ligated to borates 4, as shown in Table 1.3 The (13C) shift of C3 and

1.5 times larger than that of , presumably due to the effective
2
fixation of the dipole vector of each furan ring that resulted from the
formation of its rigid cage-structure. The Mulliken charge distribution
also reflected the difference in dipole; the Mulliken charge of the B
the stretching frequency of the carbonyl (C=O) groups in 13 clearly
show the degree of Lewis acidity. The borate
(13C) and (C=O), which indicated a Lewis acidity that was slightly
higher than that of
4 showed a large 
2
.
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atom for
(Fig. S2).
Precise tuning of the electronic features of
catalytic activities. To estimate the Lewis acid catalytic ability, the interaction in the course of a ligand-exchange pathway. We
Mukaiyama-type reaction11 of a variety of aldehydes 14a-e with performed UV measurements of
·THF under variable concentrations,
silylketene acetal 15 was examined in the presence of borate since the electronic interactions between the chromophores cause
catalysts ·THF and ·THF gave a much higher spectral changes, which in most cases results in a hypochromic
·THF.12 The borate
yield of the product 16a-d compared with that given by ·THF were recorded in CH2Cl2 in a
·THF for shift.14 The absorption spectra of
aromatic aldehydes 14a-d in a short time, although prolonging the concentration range from ca. 2.0×10-5 to 2.0×10-4 M. Under these
reaction time led to high yields even in the catalytic reaction with conditions, the longest absorption bands of ·THF at 330 280 nm,
LUMO transition (
*) via time-dependent DFT calculation (Fig. S3), exhibited
remarkable spectral changes that resulted in hypochromic effects
catalyzed a wide range of aromatic aldehydes to give the desired with slight red shifts at 330 300 nm and hyperchromic effects with
products in moderate yields in a short time. As expected from the slight blue shifts at 300 280 nm (Fig. S4(A)). On the other hand, the
theoretical analyses, the borate showed high affinity to the spectra of ·THF in CH2Cl2 exhibited no remarkable concentration
substrate and high catalytic turnover, which was accomplished via an dependence (Fig. S4(B)).15 These results suggest that the benzofuran-
effective -conjugation between the Lewis acid center and an based ·THF would benefit from self-intermolecular stabilization,
4
(+1.265 a.u.) was more positive than that of
2
(+1.161 a.u.) mechanism came from the intermolecular interaction of
4 (See also
the Supplementary Information).
4
clearly characterized its A bimolecular process requires the presence of an intermolecular
4
4
2
4
2
4
4
‒
2
·THF (Table 2). Moreover, the borate
4
·THF showed high tolerance to which were mainly assigned to the HOMO
would have limited
→
→
a
variety of functional groups. While
4

applicability to aliphatic aldehydes (entry 5), it should be noted that
4
‒
‒
4
2

4
aromatic core with a large dipole moment in the cage structure.
presumably due to its dipole-dipole interaction.16, 17
Table 2. Mukaiyama aldol reaction catalyzed by borate 4·THF.
Table 3. Mukaiyama aldol reaction catalyzed by borate 4·THF under photo
irradiation.
Finally, we describe the effect of photo irradiation on the control of
Lewis acidity. A Mukaiyama-type aldol reaction of 14c with 15 upon
exposure to black-light (centred at 365 nm) irradiation at room
temperature under the slightly modified conditions was performed.
Although no significant change in reactivity was observed in the
presence of borate
2·THF, borate 4·THF afforded 16c in a 1.7-fold
higher yield under the black-light irradiated conditions (Table 3).
While the mechanistic details of the effect of the photo-irradiation
have not been clarified, the excitation energy of
4 was lower than
that of as a result of the expanded -conjugation, as well as the
2

molecular geometry changes and charge reorientations in the first
excited state, and this may have played a main role in controlling the
Lewis acidity.
To further explore the catalytic turnover, the ligand-exchange rate
was investigated. The mixture of the complex 4·DMAP in a pyridine-
Conclusions
1
d5 solution was observed via H-NMR (Table S4). The kinetic equation
We synthesized a cage-shaped borate
4 composed of a benzofuran
based on the first order of the borate in our previous report3
framework, characterized its molecular geometry via X-ray
crystallography, and estimated its electronic features via DFT
calculations. The synthesized complex exhibited a high Lewis acidity
with a high catalytic turnover, which was confirmed via Mukaiyama-
aldol type reaction, ligand-exchange rate determination, and the
concentration dependence of the electronic absorptions. For the
unreasonably showed a large negative activation entropy, S (-33. 4
cal/K·mol),13 and, thus, the first-order hypothesis was found to be
incorrect because a step for releasing the DMAP from the ligated
complex led to an increase in entropy. Based on these results, ligand
dissociation does not proceed via a simple dissociation of the ligand
but includes the assistance of another boron complex to release the
DMAP. Based on the bimolecular contribution of the borate-to-ligand
benzofuran-based caged borate 4, an effective lowering of the next-
LUMO level and an intermolecular stabilization of the ligand-free
complex were achieved via photo activation, which allowed us to
successfully balance two conflicting aims for Lewis acid catalysts:
dissociation, kinetic analysis gave the activation parameters
G 25.4
kcal/mol, 20.3 kcal/mol, and -17.2 cal/K·mol. This unusual

H
S
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acidity and catalytic turnover. Although there is still room for
6
For some recent examples of heteroaromatic conjugated systems, see:
(a) K. Takimiya, S. Shinamura, I. Osaka and E. Miyazaki, Adv.
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improvement in the versatilities of the reactions catalyzed by 4, the
precise tuning of Lewis acid catalytic activity in association with the
introduction of heteraromatic moieties to the cage-shaped borate
core holds the potential to construct photo- or electro-responsive
Lewis acid catalysts. Theoretical studies as well as further
experimental investigations of the obtained Lewis acid catalyst are
ongoing by our group.
Yamaguchi, Chem. Asian J., 2009, 4, 1386; (d) A. Narita, X.-Y.
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Chao, Y.-S. Wen and T. J. Chow, Chem. Asian J., 2013,
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This work was supported by the Ministry of Education, Culture,
Sports, Science and Technology (Japan). This work was also
supported by the Nagase Science and Technology Foundation. A.K.
wishes to thank the Research Capability Development Project
(Professional development program for assistant professors) of
Frontier Research Center of Graduate School of Engineering, Osaka
University. We thank Dr. Nobuko Kanehisa for the valuable advice
regarding X-ray crystallography. Thanks are due to Mr. H. Moriguchi,
Faculty of Engineering, Osaka University, for assistance in obtaining
the MS spectra.
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10 The analytical data of the borate complex 4·THF is included in the
supplementary information. CCDC 1440145 contains the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Notes and references
Department of Applied Chemistry, Graduate School of Engineering,
a
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13
  
G‡ 24.6 kcal/mol, H‡ 14.9 kcal/mol, S‡ -33.4 cal/Kmol.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/c000000x/
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an intermolecular interaction, we attempted to observe the existence
of the ligand-free complex under suitable conditions; see the
Supplementary information.
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