bonding modules (usually urea derivatives) are developed
and have gained great success. In particular, Meijer’s
ureidopyrimidone (UPy) building block,6 with its character-
istics of high dimerization constant and synthetic accessibil-
ity, has found widespread applications in supramolecular
chemistry, materials science, and catalysis.7 Zimmerman’s
ureidodeazapterin8 and ureidonaphthyridine9 modules are
also successful examples of heterocyclic building blocks. To
address the tautomeric problem often accompanied with
heterocycles, Gong et al. developed an aromatic oligoamide
system.10 Many other molecular duplexes assembled by
arrays of amide units were also described.11 In addition, Li
et al. designed hydrazide-derived quadruply hydrogen-bonded
heteroduplexes.12 Recently, we reported systematic research
of molecular duplex strands and noncovalent synthesis of
shape-persistent cyclic hexamers based on the hydrazide
hydrogen-bonding motif.13
Figure 1. Chemical structures of several important hydrogen-
bonding units.
new class of multiple hydrogen-bond-mediated molecular
duplexes based on the self-complementary amidourea motif.
To our knowledge, this work represents the first successful
application of amidourea unit in the construction of molecular
duplexes.
Compounds 1 and 2, which possess one to two amidourea
units, were designed and synthesized (Figure 2). The alkoxy
As above-mentioned, most of the hydrogen-bond-mediated
molecular duplexes were based on the amide, urea, and
hydrazide units (Figure 1). However, the amidourea,14 as
another important hydrogen-bonding building block, has not
gained much attention. Continuing our interest in developing
unnatural molecular recognition systems, we herein report a
(6) (a) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.;
Hirschberg, J. H. K. K.; Lange, R. F. M.; Lowe, J. K. L.; Meijer, E. W.
Science 1997, 278, 1601–1604. (b) Beijer, F. H.; Sijbesma, R. P.; Kooijman,
H.; Spek, A. L.; Meijer, E. W. J. Am. Chem. Soc. 1998, 120, 6761–6769.
(c) So¨ntjens, S. H. M.; Sijbesma, R. P.; van Genderen, M. H. P.; Meijer,
E. W. J. Am. Chem. Soc. 2000, 122, 7487–7493.
(7) For selected examples, see: (a) Huerta, E.; Metselaar, G. A.; Fragoso,
A.; Santos, E.; Bo, C.; de Mendoza, J. Angew. Chem., Int. Ed. 2007, 46,
202–205. (b) Scherman, O. A.; Ligthart, G. B. W. L.; Ohkawa, H.; Sijbesma,
R. P.; Meijer, E. W. Proc. Nat. Acad. Sci. U.S.A. 2006, 103, 11850–11855.
(c) Wang, X.-Z.; Li, X.-Q.; Shao, X.-B.; Zhao, X.; Deng, P.; Jiang, X.-K.;
Li, Z.-T.; Chen, Y.-Q. Chem.sEur. J. 2003, 9, 2904–2913. (d) Shi, L.;
Wang, X.-W.; Sandoval, C. A.; Li, M.-X.; Qi, Q.-Y.; Li, Z.-T.; Ding, K.-
L. Angew. Chem., Int. Ed. 2006, 45, 4108–4112.
(8) (a) Corbin, P. S.; Zimmerman, S. C. J. Am. Chem. Soc. 1998, 120,
9710–9711. (b) Corbin, P. S.; Lawless, L. J.; Li, Z.-T.; Ma, Y.; Witmer,
M. J.; Zimmerman, S. C. Proc. Nat. Acad. Sci. U.S.A. 2002, 99, 5099–
5104.
(9) (a) Corbin, P. S.; Zimmerman, S. C. J. Am. Chem. Soc. 2000, 122,
3779–3780. (b) Corbin, P. S.; Zimmerman, S. C.; Thiessen, P. A.; Hawryluk,
N. A.; Murray, T. J. J. Am. Chem. Soc. 2001, 123, 10475–10488. (c) Mayer,
M. F.; Nakashima, S.; Zimmerman, S. C. Org. Lett. 2005, 7, 3005–3008.
(10) (a) Gong, B. Polym. Int. 2007, 56, 436–443, and references therein.
(b) Gong, B.; Yan, Y.-F.; Zeng, H.-Q.; Skrzypczak-Jankunn, E.; Kim, Y. W.;
Zhu, J.; Ickes, H. J. Am. Chem. Soc. 1999, 121, 5607–5608. (c) Li, M.-F.;
Yamato, K.; Ferguson, J. S.; Singarapu, K. K.; Szyperski, T.; Gong, B.
J. Am. Chem. Soc. 2008, 130, 491–500.
Figure 2. Chemical structures of 1 and 2 and representation of the
molecular duplexes, with proton-labeling scheme indicated.
(11) For selected examples, see: (a) Nowick, J. S. Acc. Chem. Res. 2008,
41, 1319–1330, and references therein. (b) Bisson, A. P.; Carver, F. J.;
Eggleston, D. S.; Haltiwanger, R. C.; Hunter, C. A.; Livingstone, D. L.;
McCabe, J. F.; Rotger, C.; Rowan, A. E. J. Am. Chem. Soc. 2000, 122,
8856–8868. (c) Zhu, J.; Lin, J.-B.; Xu, Y.-X.; Shao, X.-B.; Jiang, X.-K.;
Li, Z.-T. J. Am. Chem. Soc. 2006, 128, 12307–12313.
groups were incorporated for the formation of highly
favorable S(6)-type15 intramolecular hydrogen bonds, which
should rigidify the backbones and preorganize the amidourea
groups to facilitate the formation of molecular duplexes.
Another advantage was improving solubility in organic
solvents by the introduction of the octyloxy groups, as well
as the hexyl group in 2b. The synthesis is depicted in Scheme
1. Compound 1 was conveniently obtained in high yield by
the reaction of hydrazide 3 with phenyl isocyanate. Com-
pound 4, which was prepared from hydrazide 3b and 1,1′-
carbonyldiimidazole efficiently, was refluxed with amine 5
in CHCl3 to give compound 2 as a white solid.
(12) Zhao, X.; Wang, X.-Z.; Jiang, X.-K.; Chen, Y.-Q.; Li, Z.-T.; Chen,
G.-J. J. Am. Chem. Soc. 2003, 125, 15128–15139.
(13) (a) Yang, Y.; Yang, Z.-Y; Yi, Y.-P.; Xiang, J.-F.; Chen, C.-F.; Wan,
L.-J.; Shuai, Z.-G. J. Org. Chem. 2007, 72, 4936–4946. (b) Yang, Y.; Xiang,
J.-F.; Chen, C.-F. Org. Lett. 2007, 9, 4355–4357. (c) Yang, Y.; Chen, T.;
Xiang, J.-F.; Yan, H.-J.; Chen, C.-F.; Wan, L.-J. Chem.sEur. J. 2008, 14,
5742–5746. (d) Yang, Y.; Xiang, J.-F.; Xue, M.; Hu, H.-Y.; Chen, C.-F. J.
Org. Chem. 2008, 73, 6369–6377. (e) Yang, Y.; Xiang, J.-F.; Xue, M.;
Hu, H.-Y.; Chen, C.-F. Org. Biomol. Chem. 2008, 6, 4198–4203. (f) Yang,
Y.; Xue, M.; Xiang, J.-F.; Chen, C.-F. J. Am. Chem. Soc. 2009, 131, 12657–
12663.
(14) Amidourea derivatives were applied in anion recognitions; see: (a)
Evans, L. S.; Gale, P. A.; Light, M. E.; Quesada, R. New J. Chem. 2006,
30, 1019–1025. (b) Quinlan, E.; Matthews, S. E.; Gunnlaugsson, T. J. Org.
Chem. 2007, 72, 7497–7503.
(15) Etter, M. C. Acc. Chem. Res. 1990, 23, 120–126.
Org. Lett., Vol. 12, No. 14, 2010
3157