ORGANIC
LETTERS
2006
Vol. 8, No. 5
803-806
Aromatic Oligoureas: Enforced Folding
and Assisted Cyclization
Aimin Zhang,† Yaohua Han,† Kazuhiro Yamato,† Xiao Cheng Zeng,‡ and
Bing Gong*,†
Department of Chemistry, UniVersity at Buffalo, The State UniVersity of New York,
Buffalo, New York 14260, and Department of Chemistry,
UniVersity of Nebraska-Lincoln, Lincoln, Nebraska 68588
Received October 29, 2005
ABSTRACT
Aromatic oligoureas are forced into well-defined conformation by incorporated intramolecular hydrogen bonds. Shape-persistent tetraureas
macrocycles were obtained in a one-step [2 2] reaction in good yields.
+
In recent years the design of folded unnatural oligomers has
attracted intense interest.1-4 We5 and others4-9 have described
aromatic oligoamides that are forced into folded conforma-
tions by rigidifying the oligoamide backbones using localized
intramolecular hydrogen bonds. Similar to the amide group,
the urea group is also distinguished by its rigidity, planarity,
and hydrogen bonding capability. Indeed, the urea function-
ality has already been adopted in the design of various folded
structures. For example, peptidomimetic oligoureas were
reported to fold into helical conformations,10 and aromatic
oligoureas were designed to adopt switchable conformations11
or to cyclize into rigid macrocycles.12 Backbone-rigidified
aromatic polyureas were found to fold into a helical
conformation according to circular dichroism spectroscopy.13
Herein, we describe the design, enforced folding, and
cyclization of backbone-rigidified aromatic oligoureas con-
sisting of meta-linked benzene rings.14
† The State University of New York.
‡ University of Nebraska-Lincoln.
(1) Gellman, S. H. Acc. Chem. Res. 1998, 31, 173.
(2) Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S.
Chem. ReV. 2001, 101, 3893.
Our design is based on diarylurea moiety 1, which is
rigidified by two very strong, intramolecularly H-bonded six-
membered rings involving the urea hydrogens and the
(3) Huc, I. Eur. J. Org. Chem. 2004, 17.
(4) Sanford, A. R.; Yamato, K.; Yuan, L.; Han, Y.; Gong, B. Eur. J.
Biochem. 2004, 271, 1416.
(5) (a) Gong, B.Chem. Eur. J. 2001, 7, 4336. (b) Zhu, J.; Parra, R. D.;
Zeng, H.; Skrzypczak-Jankun, E.; Zeng, X. C.; Gong, B. J. Am. Chem.
Soc. 2000, 122, 4219.
(6) Hamuro, Y.; Geib, S. J.; Hamilton, A. D. J. Am. Chem. Soc. 1996,
118, 7529.
(7) Huc, I.; Khoury, R. G.; Krische, M. J.; Lehn, J.-M. Nature 2000,
407, 720.
(8) Jiang, H.; Le´ger, J.-M.; Dolain, C.; Guionneau, P.; Huc, I. Tetrahedron
2003, 59, 8365.
(10) Boeijen, A.; Liskamp, R. M. J. Eur. J. Org. Chem. 1999, 2127.
(11) Corbin, P. S.; Zimmerman, S. C.; Thiessen, P. A.; Hawryluk, N.
A.; Murray, T. J. J. Am. Chem. Soc. 2001, 123, 10475.
(12) Xing, L. Y.; Ziener, U.; Sutherland,T. C.; Cuccia, L. A. Chem.
Commun. 2005, Advance article. Published on the web 10/20/2005.
(13) van Gorp, J. J.; Vekemans, J. A. J. M.; Meijer, E. W. Chem.
Commun. 2004, 60.
(14) Yuan, L. H.; Zeng, H. Q.; Yamato, K.; Sanford, A. R.; Feng, W.;
Atreya, H. S.; Sukumaran, D. K.; Szyperski, T.; Gong, B. J. Am. Chem.
Soc. 2004, 126, 16528.
(9) Yi, H. P.; Shao, X. B.; Hou, J. L.; Li, C.; Jiang, X. K.; Li, Z. T. New
J. Chem. 2005, 29, 1213.
10.1021/ol0526322 CCC: $33.50
© 2006 American Chemical Society
Published on Web 02/07/2006