and N-butylpyrrolidinone (NBP).3 In the next year, Wang et
al. reported 3-borono-N-methylpyridinium iodide (3) and
N-polystyrene resin-bound 3-boronopyridinium chloride (4)
as amide condensation catalysts.4
ronic acids, 6 and 7, were less active than the corresponding
boronopyridinium iodides (entries 3 and 4). The catalytic
activity of 7 was quite low, probably because of its low
solubility under these reaction conditions.
We report here that N-alkyl-4-boronopyridinium salts are
more thermally stable than N-alkyl-3-boronopyridinium salts.
We found that a homogeneous catalyst 2 could be reused
through the use of ionic liquid-toluene biphasic solvents. Fur-
thermore, we developed N-polystyrene resin-bound 4-borono-
pyridinium salts 5a-d as heterogeneous and reusable amide
condensation catalysts without the need for ionic liquids.
According to some reports,5 the thermostability of py-
ridineboronic acids for hydrolytic protodeboration increases
in the order 2-pyridineboronic acid , 3-pyridineboronic acid
(6) < 4-pyridineboronic acid (7). First, the thermostability
of N-methyl boronopyridinium iodides was investigated
under heating conditions at 120 °C in DMF. The half-life of
2 was 8 h under the above conditions. On the other hand, 3
was completely decomposed to boric acid and N-methylpy-
ridinium iodide within 8 h via hydrolytic protodeboration.
In contrast, 6 and 7 were stable even after heating at 120 °C
for 1 day. 2-Borono-N-methylboronopyridinium iodide could
not be prepared from 2-pyridineboronic acid because of its
high sensitivity to hydrolysis. Thus, we determined their
thermostabilities, which increased in the order 2-pyridinebo-
ronic acid , 3 < 2 < 6 e 7.
In the course of the experiment in which 2 was heated in
DMF at 120 °C, we observed that 2 completely changed to
a yellow precipitate within 1 h and then gradually underwent
hydrolytic deboration. We isolated this yellow precipitate
as an orange crystal from water. Surprisingly, the crystal was
unambiguously confirmed to be a dodecamer of 2, [2]12, by
single-crystal X-ray diffraction (Figure 2). To the best of
Figure 1. Thermally stable and reusable boronopyridinium salt
catalysts 2 and 5a-d.
our knowledge, this is the first example of a dodecamer of
an arylboronic acid. Interestingly, [2]12 was dissolved and
stable even in water because the 12 hydrophilic pyridinium
ion moieties were oriented on the outside of [2]12.
Next, the catalytic activities of pyridineboronic acids and
boronopyridinium iodides were examined for the model
amide condensation reaction of cyclohexanecarboxylic acid
with benzylamine in 5:1 (v/v) biphasic solvents of toluene
and 1-ethyl-3-methylimidazolium trifluoromethanesulfonate
[emim][OTf]. The reactions were carried out under azeo-
tropic reflux conditions with the removal of water for 2 h.
The results are shown in Table 1. As expected, 2 was the
Table 1. Catalytic Activity of Boronic Acids
Figure 2. X-ray crystal structure of dodecamer [2]12,
[CH3NC5H4BO14/12]12I8‚10H2O. Water is omitted for clarity.
a 7 did not dissolve under these conditions.
Next, the catalytic activities of 2 and [2]12 (5 mol % for
B-atom) were compared in the amide condensation of
4-phenylbutyric acid with benzylamine under azeotropic
reflux conditions in toluene with the removal of water (entries
1 and 2, Table 2). The catalytic activity of [2]12 was much
lower than that of 2. Fortunately, the catalytic activities of 2
and [2]12 were dramatically improved in biphasic solvents
most active catalyst (entry 1). The catalytic activity of 3 was
slightly lower than that of 2 (entry 2). 3- and 4-Pyridinebo-
(4) Latta, R.; Springsteen, G.; Wang, B. Synthesis 2001, 1611-1613.
(5) (a) Ishiyama, T.; Ishida, K.; Miyaura, N. Tetrahedron 2001, 57,
9813-9816. (b) Bouillon, A.; Lancelot, J.-C.; de Oliveria Santos, J. S.;
Collot, V.; Bovy, P. R.; Rault, S. Tetrahedon 2003, 59, 10043-10049. (c)
Gros, P.; Doudouth, A.; Fort, Y. Tetrahedron Lett. 2004, 45, 6239-6241.
5044
Org. Lett., Vol. 7, No. 22, 2005
Maki, Toshikatsu
