Regioselective introduction of two boronic acid groups into [60]fullerene using
saccharides as imprinting templates
Tsutomu Ishi-i, Kazuaki Nakashima and Seiji Shinkai*†
Chemotransfiguration Project, Japan Science and Technology Corporation (JST), 2432 Aikawa, Kurume, Fukuoka 839, Japan
Two boronic acid groups were introduced into [60]fullerene
using saccharides as template molecules: it was found that
the regioselectivity changes depending on the saccharide
structure.
In the HPLC analysis, 7–8 peaks were always observable and
the relative intensity changed depending on the saccharide used
as the template molecule. Compounds 6, 7 and 8 with d-threitol,
d-mannito 3,4-carbonate and 3-O-methyl-d-glucofuranose as
template molecules, respectively, afforded major peaks for Peak
7 (47.3%), Peak 8 (55.7%) and Peak 6 (72.5%), respectively,
whereas compound 9 with 1-O-methyl-a-d-mannopyranoside
as a template molecule featured a rather nonselective product
distribution. The results imply that the saccharide changes the
distance between two o-xylenyl dibromide groups in 6–9 and
the addition reaction occurs at different CNC double bonds on
the [60]fullerene surface.
It is difficult to isolate the eight different isomers of
disubstituted 12 and thus identify the structure of each isomer.
We decided to attempt the isolation of Peak 6 [with the highest
(72.5%) yield] in the mixture obtained from 8 and [60]fullerene.
Through trial and error it was found that Peak 6 can be isolated
by recrystallisation from n-hexane–CH2Cl2: the HPLC analysis
showed a single peak for Peak 6. In the 1H NMR spectrum (300
MHz, [2H8]toluene, 90 °C) of this compound (12a) one could
observe one CH3 proton peak (d 0.71, 12 H) and one CH2 proton
peak (d 3.50, 8 H) for the protective groups and four CH2 proton
peaks (d 4.04, 4.04, 4.12 and 4.19, 2 H each) and three ArH
proton peaks (d 7.42, 8.13 and 8.17, 2 H each) for the o-xylenyl
groups. This splitting pattern is commensurate with either C2
symmetry(cis-3, trans-2ortrans-3)orCs symmetry(cis-1, cis-2,
The molecular imprinting technique attracted considerable
attention in the 1970s, but recently has been revived as an active
research area.1–3 The principle involves copolymerisation of
vinyl monomers with divinyl monomers in the presence of guest
metals or molecules to produce three-dimensional network
polymers.1–3 Although this technique has achieved some degree
of success, two complex problems have been left unresolved,
i.e. the evaluation of the imprinting effect is difficult because it
can be performed only in a heterogeneous system, and the
storage capacity is small because only the particle surface is
useful for the re-binding of guests. Is there an alternate method
in which both the imprinting process and the estimation process
can be carried out in a more reliable homogeneous system?
[60]Fullerene and its homologues are moderately soluble in
organic solvents and have plenty of reactive CNC double bonds
which are useful for the immobilisation of functional groups. It
thus occurred to us that they would be useful as a base for the
imprinting of functional groups and for use in a homogeneous
system. There are a limited number of precedents for re-
gioselective introduction of substituents into [60]fullerene.4–6
In order to apply [60]fullerene to the memory storage, we here
chose saccharides as the template and guest molecules and
boronic acids as the functional groups. Saccharides have several
specific advantages for the present purpose which other
template molecules do not have, i.e. (i) they can arrange two
boronic acid groups in a variety of spatial positions, (ii) removal
and re-binding can occur reversibly, and (iii) because of their
inherent chirality, chiroselective introduction of two boronic
acid groups is possible.7 We here report the fact that, using
saccharides as template molecules, two boronic acid groups can
be regioselectively introduced into [60]fullerene; the regio-
spectrum is closely related to the structure of saccharides used
as template molecules.
HO
OH
O
O
O
O
Br
B
B
B
i–iii
iv
v
Br
Br
1
2
3
4
Br
Br
Br
Br
Saccharide
O
B
B
O
O
In order to access saccharide–boronic acid 1:2 complexes
6–9, we first synthesised 5 from 4-bromo-o-xylene 1 (Scheme
1). Compound 5, which was isolated as a cyclic trimer,7,8 was
O
O
B
vii
vi
B
B
O
O
Ar
Ar
1
identified by H NMR, IR (KBr) and mass (negative SIMS)
spectral evidence and elemental analysis. Complexes 6–9 were
synthesised from 5 and the corresponding saccharides in
refluxing toluene with azeotropic removal of water under a
Br
Br
Ar =
Br
Br
5
O
O
1
nitrogen atmosphere. The products were identified by H and
O
Ar
11B NMR and IR (KBr) spectral evidence and elemental
analyses.9 The reaction of 6–9 with [60]fullerene was carried
out in refluxing toluene for 40 h in the presence of 18-crown-6
and KI under a nitrogen atmosphere. To simplify the product
analysis, the saccharides were removed by the treatment with
aqueous 1.2 mol dm23 HCl solution and then the boronic acid
groups in the product 11 were protected using 2,2-dimethyl-
propane-1,3-diol10 (Scheme 2). The product was purified by
column chromatography. We thus isolated a regioisomeric
mixture of 12 in 49–58% yield. This mixture was subjected to
HPLC analysis [COSMOSIL 5 PBB, n-hexane–toluene (3:7
v/v)]. The results are summarised in Table 1.
B
O
Ar
B
Ar
B
O
OMe
O
O
O
O
O
B
H
H
O
O
O
O
O
O
O
Ar
O
O
O
O
B
B
B
Ar
B
Ar
MeO
Ar
Ar
6
7
8
9
Scheme 1 Reagent and conditions: i, Mg, THF; ii, B(OMe)3, 260 °C; iii,
H2SO4, 69% from 1; iv, propane-1,3-diol, toluene, reflux, 71%; v, NBS,
CCl4, reflux, 50%; vi, HCl, THF, 90%; vii, saccharide, toluene, reflux, 82%
for 6, 95% for 7, 76% for 8 and 60% for 9
Chem. Commun., 1998
1047
Ishi-i, Tsutomu
