Dynamic covalent chemistry of a boronylammonium ion and a crown ether: formation of a C3-symmetric [4]rotaxane

Article abstract of DOI:10.1016/j.tetlet.2008.03.106

This Letter describes an efficient method for constructing a C₃-symmetric [4]rotaxane through hydrogen bond-guided self-assembly and boroxine formation. The reactions proceed under mild conditions in solution, with entropically driven forces promoting the formation of the [4]rotaxane.

Full text of DOI:10.1016/j.tetlet.2008.03.106

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3449–3452
Dynamic covalent chemistry of a boronylammonium ion
and a crown ether: formation of a C3-symmetric [4]rotaxane
a,
a
b
b
*
Yuji Tokunaga , Takashi Ito , Hidetoshi Sugawara , Ryuji Nakata
a Department of Materials Science and Engineering, Faculty of Engineering, University of Fukui, Fukui 910-8507, Japan
b Natural Science Education Laboratory, Faculty of Education and Regional Studies, University of Fukui, Fukui 910-8507, Japan
Received 23 January 2008; revised 15 March 2008; accepted 21 March 2008
Available online 28 March 2008
Abstract
This Letter describes an efficient method for constructing a C3-symmetric [4]rotaxane through hydrogen bond-guided self-assembly
and boroxine formation. The reactions proceed under mild conditions in solution, with entropically driven forces promoting the forma-
tion of the [4]rotaxane.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Dynamic covalent chemistry; Rotaxane; Hydrogen bonding; Boroxine
Dynamic covalent chemistry is a powerful method for
synthesizing thermodynamically stable products selectively
from among a set of potential products.1 In particular, it is
very effective for constructing and functionalizing mechan-
ically interlocked molecules, such as catenanes and rotax-
anes, through bond dissociation/recombination processes.
Various reactions leading to covalent connection between
reactants have been demonstrated, including olefin meta-
thesis,2 imine3 and hydrazone4 formation, thiol–disulfide
interchange,5 transacetalation,6 tritylation of thioethers,7
and coordinative bond formation.8
formation ([4]rotaxane construction)—to synthesize a C3-
symmetric [4]rotaxane containing a boroxine core (Scheme
1), and used 1H NMR spectroscopy to determine this inter-
locked molecule’s thermodynamic stability.
The preparation of the key secondary dialkylammonium
salt 1ꢀPF6 was initiated through the condensation of 4-
formylphenylboronic acid with 3,5-dimethylbenzylamine
to afford the corresponding imine. Reduction of this imine,
Boroxines are six-membered-ring inorganic hetero-
cycles; their attractive C3-symmetric tripodal structures are
readily prepared through the dehydration of corresponding
boronic acids. Recently, we reported the reversible conden-
sation of different boronic acids at room temperature to
give their corresponding boroxines; the trimerization of
pairs of these boronic acids allowed us to prepare a unique
dynamic combinational library.9 In this present study, we
used two reversible processes—hydrogen bond-guided
self-assembly ([2]pseudorotaxane formation) and boroxine
3
B(OH)2
+
3
3
B(OH)2
B
+
O
B
O
B
3H2O
O
*
Corresponding author. Tel./fax: +81 776 27 8611.
Scheme 1.
E-mail address: tokunaga@matse.u-fukui.ac.jp (Y. Tokunaga).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.106

3450
Y. Tokunaga et al. / Tetrahedron Letters 49 (2008) 3449–3452
shift assignments are consistent with those reported previ-
B(OH)2
-
ously for structurally similar systems.2d,e,3c,5b,c,7 To assign
specific resonances to the protons of [2]pseudorotaxane
2ꢀPF6 and [4]rotaxane 3ꢀPF6, we recorded a 1H NMR spec-
trum of the mixture in the presence of an excess of D2O
(Fig. 1c), which hydrolyzed the boroxine. The ESI mass
spectrum of a mixture of 1ꢀPF6 and DB24C8 in dichloro-
methane confirmed the presence of the [2]pseudorotaxane
and [4]rotaxane structuresþ, which were represented by
peaks for their [MꢁPF6ꢁꢂ ions at m/z 718 and 2391,
respectively.10
Cl
+
+
NH3
OHC
1) Et3N, MgSO4
2) NaBH4
3) HCl
4) NH4PF6
60%
B(OH)2
-
PF6
H2
N
+
.
1 PF6
Next, we calculated the equilibrium constant (Keq) for
boroxine
formation
(3 ꢃ 2ꢀPF6 ¡ 3ꢀPF6 + 3H2O)11
Scheme 2.
through the integration of the signals for 2ꢀPF6, 3ꢀPF6,
water, and an internal standard (trimethyl 1,3,5-benzenetri-
1
carboxylate) in H NMR spectra recorded at 10–35 °C. A
followed by protonation and counterion exchange, pro-
duced the ammonium salt 1ꢀPF6, which possessed a bulky
aryl group at one end and a boronyl group at the other
(Scheme 2).
plot of DG versus temperature for the equilibria (boroxine
formation) yielded a straight line (Fig. 2), from which we
determined the enthalpic (DH = 2.53 0.63 kJ/mol) and
entropic (DS = 132 2 J/mol K) parameters. Consistent
with the findings reported previously, the formation of this
boroxine is an entropically driven process because of the
release of three free water molecules into the bulk
solvent.9,12,13
In an initial experiment using chloroform as the solvent,
we validated the feasibility of forming the boroxine from
the [2]pseudorotaxane formed from the dialkylammonium
ion 1ꢀPF6 and dibenzo[24]crown-8 (DB24C8). We sus-
pected that [2]pseudorotaxane 2ꢀPF6 formed in solution
because the dialkylammonium salt 1ꢀPF6 is insoluble in
chloroform in the absence of the crown ether; that is,
1ꢀPF6 was solubilised upon complexation with DB24C8.
The cyclotrimerization of [2]pseudorotaxane 2ꢀPF6 pro-
ceeded (Scheme 3) while sonicating a mixture of 1ꢀPF6
and an excess of DB24C8 in CDCl3 for four hours until
a disappearance of the solid. We confirmed the structures
of 2ꢀPF6 and 3ꢀPF6 from spectroscopic and analytical data.
It has been reported that the presence of an electron-
donating group in the para position of the phenyl ring
increases the thermodynamic stability of triphenylboroxine
derivatives toward hydrolysis;9 computational studies sup-
port this empirical finding.11,14 The equilibrium constant
(Keq: 1.32 0.33 M) for the formation of 3ꢀPF6 from
2ꢀPF6 is, however, similar to that for the cyclotrimerization
of p-methoxyphenylboronic acid, which possesses such an
electron-donating group (for examples of Keq value, p-
methoxyphenylboronic acid: 1.40 M, p-tolylboronic acid:
0.45 M).15 We suspect that several factors are responsible
for this phenomenon: (1) the benzene rings of the
DB24C8 and dumbbell-shaped units interact to enhance
the electron density of the aromatic rings connected to
the boroxine core; (2) hydrogen bonds to the crown ether
unit weaken the electron-withdrawing properties of the
1
Figure 1a displays the H NMR spectrum of a mixture
of 1ꢀPF6 and DB24C8. By comparing the spectrum of
DB24C8 with that of the mixture, we observe two sets of
resonances, which we assigned to the [2]pseudorotaxane
2ꢀPF6 and [4]rotaxane 3ꢀPF6. The CH2N protons of the
dumbbell-shaped units appear at 4.36 and 4.63 ppm for
[2]pseudorotaxane 2ꢀPF6 and at 4.48 and 4.75 ppm for
[4]rotaxane 3ꢀPF6, with the corresponding aromatic pro-
tons at 7.39 and 7.76 ppm for 2ꢀPF6 and 7.59 and
8.14 ppm for 3ꢀPF6. The resonances of the aliphatic and
aromatic protons of the DB24C8 components appear at
3.30–3.67 and 6.50–6.68 ppm, respectively. These chemical
þ
CH2NH2 moieties; (3) the DB24C8 units provide steric
stabilization against the hydrolysis of the boroxine.
In summary, we have constructed a C3-symmetric
[4]rotaxane 3ꢀPF6 using two reversible processes: [2]pseudo-
-
B
-
O
B
O
B
PF6
PF6
O O
O O
H2
B(OH)2
.
1 PF6
H2
O
O
O
O
O
N
O
N
+
+
+
O
O
O
+ 3H2O
DB24C8
O O
O O
.
2 PF6
.
3
3 PF6
.
[3 PF6] [H2O]
K
=
3
.
[2 PF6]
Scheme 3.

Y. Tokunaga et al. / Tetrahedron Letters 49 (2008) 3449–3452
3451
Hh
-
O
B
PF6
O O
Hf
H2
O
O
O
O
N
+
Hd
O
Ha
Hb
Hc
O O
NOE
.
.
2 PF6 and 3 PF6
a
b
c
Fig. 1. 1H NMR spectra (500 MHz, CDCl3) of a mixture of the boronic acid 1ꢀPF6 (10 mM) and DB24C8 (30 mM) at (a) 25 and (b) 45 °C and (c) in the
presence of an excess of D2O at 25 °C. j: [4]rotaxane 3ꢀPF6; h: [2]pseudorotaxane 2ꢀPF6; s: DB24C8.
3.00
rotaxane formation mediated by hydrogen bonding
between DB24C8 and a boronic acid-functionalized dialky-
1.00
lammonium ion and boroxine formation through cyclo-
trimerization of three boronic acid units. Variable-
temperature NMR spectroscopy experiments provided us
-1.00
with the thermodynamic parameters for the boroxine
formation process; it appears that the structure of the C3-
-3.00
symmetric [4]rotaxane 3ꢀPF6 stabilizes the boroxine core
against hydrolysis.
-5.00
5
10
15
20
25
30
35
40
T (oC)
Supplementary data
Fig. 2. Plots of DG versus temperature for boroxine formation. The
experiments were performed four times. Concentration data were obtained
from integration of the appropriate signals for 2ꢀPF6, 3ꢀPF6, water, and
the internal standard (trimethyl 1,3,5-benzenetricarboxylate) in the 1H
NMR spectra recorded in CDCl3.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2008.
03.106.

3452
Y. Tokunaga et al. / Tetrahedron Letters 49 (2008) 3449–3452
Oku, T.; Furusho, T.; Takata, T. Angew. Chem., Int. Ed. 2004, 43,
References and notes
966–969.
6. Fuchs, B.; Nelson, A.; Star, A.; Stoddart, J. F.; Vidal, S. Angew.
Chem., Int. Ed. 2003, 42, 4220–4224.
7. Furusho, Y.; Oku, T.; Rajkumar, G. A.; Takata, T. Chem. Lett. 2004,
33, 52–53.
1. For selected reviews, see: (a) Rowan, S. J.; Cantrill, S. J.; Cousins, G.
R. L.; Sanders, J. K. M.; Stoddart, J. F. Angew. Chem., Int. Ed. 2002,
41, 898–952; (b) Lehn, J.-M. Chem. Eur. J. 1999, 5, 2455–2463; (c)
Otto, S.; Furlan, R. L. E.; Sanders, J. K. M. Curr. Opin. Chem. Biol.
2002, 6, 321–327; (d) Karan, C.; Miller, B. L. Drug Discovery Today
2000, 5, 67–75.
2. (a) Wisner, J. A.; Beer, P. D.; Drew, M. G. B.; Sambrook, M. R. J.
Am. Chem. Soc. 2002, 124, 12469–12476; (b) Kilbinger, A. F. M.;
Cantrill, S. J.; Waltman, A. W.; Day, M. W.; Grubbs, R. H. Angew.
Chem., Int. Ed. 2003, 42, 3281–3285; (c) Iwamoto, H.; Itoh, K.;
Nagamiya, H.; Fukazawa, Y. Tetrahedron Lett. 2003, 44, 5773–5776;
(d) Hou, H.; Leung, K. C.-F.; Lanari, D.; Nelson, A.; Stoddart, J. F.;
Grubbs, R. H. J. Am. Chem. Soc. 2006, 128, 15358–15359; (e) Guidry,
E. N.; Li, J.; Stoddart, J. F.; Grubbs, R. H. J. Am. Chem. Soc. 2007,
129, 8944–8945; (f) Kidd, T. J.; Leigh, D. A.; Wilson, A. J. J. Am.
Chem. Soc. 1999, 121, 1599–1600; (g) Wang, L.; Vysotsky, M. O.;
Bogdan, A.; Bolte, M.; Bo¨hmer, V. Science 2004, 304, 1312–1314.
3. (a) Horn, M.; Ihringer, J.; Glink, P. T.; Stoddart, J. F. Chem. Eur. J.
8. For examples, see: (a) Fujita, M.; Fujita, N.; Ogura, K.; Yamaguchi,
K. Nature 1999, 400, 52–55; (b) Hunter, C. A.; Low, C. M. R.;
Packer, M. J.; Spey, S. E.; Vinter, J. G.; Vysotsky, M. O.; Zonta, C.
Angew. Chem., Int. Ed. 2001, 40, 2678–2682; (c) Chang, S.-Y.; Choi, J.
S.; Jeong, K.-S. Chem. Eur. J. 2001, 7, 2687–2697; (d) McArdle, C. P.;
Van, S.; Jennings, M. C.; Puddephatt, R. J. J. Am. Chem. Soc. 2002,
124, 3959–3965; (e) Park, K.-M.; Kim, S.-Y.; Heo, J.; Whang, D.;
Sakamoto, S.; Yamaguchi, K.; Kim, K. J. Am. Chem. Soc. 2002, 124,
2140–2147; (f) Blanco, V.; Chas, M.; Abella, D.; Peinador, C.;
Quintela, J. M. J. Am. Chem. Soc. 2007, 129, 13978–13986.
9. (a) Tokunaga, Y.; Ueno, H.; Shimomura, Y.; Seo, T. Heterocycles
2002, 57, 787–790; (b) Tokunaga, Y.; Ueno, H.; Shimomura, Y.
Heterocycles 2007, 74, 219–223.
2þ
3þ
10. Peaks for [Mꢁ2PF6ꢁꢂ
and [Mꢁ3PF6ꢁꢂ
ions of 3ꢀPF6 were
observed at m/z 1123 and 700, respectively. See supplementary data.
11. The equilibrium process includes many spices. We simplify the
equilibrium, because these intermediates are not stable to detect, see:
Kua, J.; Gyselbrecht, C. R. J. Phys. Chem. A 2007, 111, 4759–4766.
12. The entropy value is larger than those of usual boroxines. Although
these results are unclear as yet, it seems that bulky functionality of
3ꢀPF6 disturbs the solvation and/or hydration.
´
2003, 9, 4046–4054; (b) Leung, K. C.-F.; Arico, F.; Cantrill, S. J.;
Stoddart, J. F. J. Am. Chem. Soc. 2005, 127, 5808–5810; (c) Cantrill,
S. J.; Rowan, S. J.; Stoddart, J. F. Org. Lett. 1999, 1, 1363–1366; (d)
Rowan, S. J.; Stoddart, J. F. Org. Lett. 1999, 1, 1913–1916; (e) Glink,
P. T.; Oliva, A. I.; Stoddart, J. F.; White, A. J. P.; Williams, D. J.
´
Angew. Chem., Int. Ed. 2001, 40, 1870–1875; (f) Arico, F.; Chang, T.;
Cantrill, S. J.; Khan, S. I.; Stoddart, J. F. Chem. Eur. J. 2005, 11,
4655–4666; (g) Hutin, M.; Schalley, C. A.; Bernardinelli, G.;
Nitschke, J. R. Chem. Eur. J. 2006, 12, 4069–4076; (h) Kawai, H.;
Umehara, T.; Fujiwara, K.; Tsuji, T.; Suzuki, T. Angew. Chem., Int.
Ed. 2006, 45, 4281–4286.
13. Molecular sieves was used to shift the equilibrium in favour of the
[4]rotaxane. However, we could not isolate the [4]rotaxane until now,
because molecular sieves may absorb HPF6 from the ammonium salt.
14. Kua, J.; Iovine, P. M. J. Phys. Chem. A 2005, 109, 8938–8943.
15. We tried to compare the stability of boroxine 3ꢀPF6 with that of
boroxine from ammonium salts 1ꢀPF6 using acetonitrile as a solvent,
directly. However, any signals based on [4]rotaxane 3ꢀPF6 were
observed in the 1H NMR spectrum of a mixture of DB24C8 and
1ꢀPF6 at room temperature.
4. Lam, R. T. S.; Belenguer, A.; Roberts, S. L.; Naumann, C.; Jarrosson,
T.; Otto, S.; Sanders, J. K. M. Science 2005, 308, 667–669.
5. (a) Kolchinski, A. G.; Alcock, N. W.; Roesner, R. A.; Busch, D. H.
Chem. Commun. 1998, 1437–1438; (b) Furusho, Y.; Hasegawa, T.;
Tsuboi, A.; Kihara, N.; Takata, T. Chem. Lett. 2000, 29, 18–19; (c)