Angewandte
Chemie
DOI: 10.1002/anie.201200346
Molecular Recognition
Recognition of Aromatic Compounds by p Pocket within a Cage-
Shaped Borate Catalyst**
Hideto Nakajima, Makoto Yasuda,* Ryosuke Takeda, and Akio Baba*
Molecular recognition contributes greatly to various fields in
nature and artificial synthesis. Enzymes utilize an affinity for
chemical bonding and steric demand to distinguish an
appropriate target.[1] In addition, metal complexes have
been often applied to the selective recognition of targeted
molecules.[2] In almost all cases, useful protocols involve
metal–heteroatom binding[3,4] and steric interactions between
the ligands and the targeted molecules.[5] Namely, the
recognition has been shown in terms of electronic or steric
factors. However, metal complexes have never been applied
to the discrimination between similarly sized aromatic and
aliphatic aldehydes that have no functional anchors. To
overcome this problem, we focused on clathrate compounds
such as molecular clips,[6] molecular tweezers,[7] and cyclo-
phanes,[8] which are known to recognize aromatic compounds
within their p-space cavity through aromatic–aromatic inter-
actions. The combination of a Lewis acid and clathrate
compounds, giving compound A, could lead to a new strategy
for a selective reaction of aromatic over aliphatic compounds
(Scheme 1). The metal center of the Lewis acid in A is
expected to capture certain aldehydes through the usual
carbonyl–acid interaction, and a “p pocket” surrounded by
aromatic moieties should distinguish aromatic over aliphatic
aldehydes. However, to use compound A as a practical
catalyst, the careful adjustment of both the strength of the
Lewis acid and p affinity is required.
Recently, we designed a tripodal cage-shaped metal
complex, B, which finely tunes Lewis acidity by changing
the structure or substituents.[9] The cage-shaped complexes B
have rigid structures; thus, we expected a high potential for
the creation of a p pocket by introducing various aromatic
substituents at appropriate positions as shown for the version
of A with a cage (Scheme 1). Furthermore, the back-shielding
framework of the cage effectively blocks the attack of the
aldehydes from the opposite side of the p pocket. Herein, we
report the synthesis of Lewis acid catalysts that selectively
recognize aromatic aldehydes and are applied to an unpre-
cedented substrate-selective reaction. The properties of the
recognition site can be tuned by introducing various aryl
groups to the cage-shaped complexes.
We chose a hetero-Diels–Alder addition as a model
reaction for distinguishing an aromatic aldehyde from an
aliphatic one. The competitive reaction between butanal (1)
and benzaldehyde (2a), which have similar steric demands,[10]
with Danishefskyꢀs diene 3[11] to produce cycloadducts 4 and
5a, respectively, was studied (Table 1).[12] The previously
reported cage-shaped borate catalyst 6B·THF (10 mol%),
having no p pocket,[9a,b,d,13] gave the products in a 73% yield
with a 5a/4 ratio of 0.92:1 when dichloromethane was used as
the solvent (entry 1). This result seemed reasonable as the two
aldehydes, 1 and 2a, had similar affinities to the boron center.
Next, the phenyl-substituted cage-shaped borate 7B·THF was
used as a catalyst (10 mol%) in dichloromethane and
afforded the products 5a and 4 in a ratio of 2.37:1
(entry 5).[14] The increase in the amount of 5a suggests that
there is a p-pocket effect given by the three phenyl rings.
Gratifyingly, this selectivity is the first example of the
recognition of an aromatic aldehyde over an aliphatic one
in a catalytic manner. An interesting difference between the
catalysts 6B·THF and 7B·THF was observed with respect to
the solvents employed. In the case of 6B·THF, the use of
coordinating solvents like diethylether, THF, and 1,4-dioxane
decreased the yields of the addition product from 73% to
around 20% (entries 2–4). In particular the yield of the
adduct 5a decreased from 35% to around 0%. In contrast, no
change in the yield was observed when different solvents were
used in the reactions with 7B·THF (entries 5–8). These results
suggest that the phenyl substituents in 7B·THF blocked the
external solvent from coordinating to the boron center and
accelerated the reaction of benzaldehyde more effectively
Scheme 1. Concept of a catalyst having a p pocket as a recognition
site.
[*] H. Nakajima, Dr. M. Yasuda, R. Takeda, Prof. Dr. A. Baba
Department of Applied Chemistry
Graduate School of Engineering, Osaka University
2-1 Yamadaoka, Suita, Osaka (Japan)
E-mail: yasuda@chem.eng.osaka-u.ac.jp
[**] This work was supported by a Grant-in-Aid for Scientific Research on
Innovative Areas (No. 23105525, “Molecular Activation Directed
toward Straightforward Synthesis” and No. 22106527, “Organic
Synthesis Based on Reaction Integration. Development of New
Methods and Creation of New Substances”), and by Scientific
Research (No. 21350074) from the Ministry of Education, Culture,
Sports, Science and Technology (Japan). 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. H.N. thanks
the Yoshida Scholarship Foundation and the Global COE Program
of Osaka University.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2012, 51, 3867 –3870
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3867