Table 3 One-pot preparationa of pentamer 6 from monomer 6a
Notes and references
1 For reviews on H-bonded macrocycles, see (a) Z. T. Li, J. L. Hou,
C. Li and H. P. Yi, Chem.–Asian J., 2006, 1, 766; (b) S. M. Hecht
and I. Huc, Foldamers: Structure, Properties and Applications,
Wiley-VCH, Weinheim, Germany, 2007; (c) A. R. Sanford and
B. Gong, Curr. Org. Chem., 2003, 7, 1649.
Entry
Solvent
Volume/ml
Yieldb (%)
1
2
3
4
5
6
CH2Cl2
DMF
CH2Cl2 + DMF
CH2Cl2 + DMF
CH3CN + DMF
CH2Cl2 + CH3CN
3
3
0
2
3
10
3
5
3 + 1
6 + 1
3 + 1
3 + 3
2 For examples of one-pot macrocyclizations, see (a) F. J. Carver,
C. A. Hunter and R. J. Shannon, Chem. Commun., 1994, 1277;
(b) L. Yuan, W. Feng, K. Yamato, A. R. Sanford, D. Xu, H. Guo
and B. Gong, J. Am. Chem. Soc., 2004, 126, 11120; (c) H. Jiang,
J. M. Leger, P. Guionneau and I. Huc, Org. Lett., 2004, 6, 2985;
(d) L. Y. Xing, U. Ziener, T. C. Sutherland and L. A. Cuccia, Chem.
Commun., 2005, 5751; (e) A. M. Zhang, Y. H. Han, K. Yamato,
X. C. Zeng and B. Gong, Org. Lett., 2006, 8, 803; (f) J. K. H. Hui
and M. J. MacLachlan, Chem. Commun., 2006, 2480; (g) H. C. Ahn,
S. M. Yun and K. Choi, Chem. Lett., 2008, 10; (h) W. Feng,
K. Yamato, L. Q. Yang, J. S. Ferguson, L. J. Zhong, S. L. Zou,
L. H. Yuan, X. C. Zeng and B. Gong, J. Am. Chem. Soc., 2009,
131, 2629; (i) A. Filarowski, A. Koll and L. Sobczyk, Curr. Org.
Chem., 2009, 13, 172; (j) J. S. Ferguson, K. Yamato, R. Liu, L. He,
X. C. Zeng and B. Gong, Angew. Chem., Int. Ed., 2009, 48, 3150;
(k) F. Li, Q. Gan, L. Xue, Z.-M. Wang and H. Jiang, Tetrahedron
Lett., 2009, 50, 2367; (l) S. Guieu, A. K. Crane and
M. J. MacLachlan, Chem. Commun., 2011, 47, 1169; (m) B. Qin,
W. Q. Ong, R. J. Ye, Z. Y. Du, X. Y. Chen, Y. Yan, K. Zhang,
H. B. Su and H. Q. Zeng, Chem. Commun., 2011, 47, 5419;
(n) B. Qin, C. Sun, Y. Liu, J. Shen, R. J. Ye, J. Zhu, X.-F. Duan
and H. Q. Zeng, Org. Lett., 2011, 13, 2270; (o) B. Qin, S. Shen,
C. Sun, Z. Y. Du, K. Zhang and H. Q. Zeng, Chem.–Asian J., 2011,
DOI: 10.1002/asia.201100409.
a
Reaction conditions: 6a (0.2 mmol), BOP (0.4 mmol), DIEA
b
(0.8 mmol), solvent, room temperature, 30 hours. Isolated yield by
washing with CH2Cl2 and MeOH.
of monomers of another type.2n,o To assess the applicability of
a chain-growth mechanism to the BOP-mediated macrocyclization,
dimer 2f composed of two units of 2a was reacted with three
equivalents of 5a in CH2Cl2 (Schemes S4 and S5, ESIw).
Statistically, pentamer 5 could be a possible product along
with other two hybrid pentamers 7 and 8 consisting of mixed
units of 2a and 5a with a ratio of 1 : 3 and 2 : 1, respectively,
and a predominant production of 7 (2a : 5a = 1 : 3) would be
consistent with a chain-growth mechanism. Analyses by
1
HRMS, H NMR and TLC of the reaction mixture confirm
7 as the major product with pentamers 5, 7 and 8 produced in
a molar ratio of 2 : 8 : 5 (Scheme S5 and Fig. S1 and S2, ESIw),
suggesting that BOP-mediated one-pot macrocyclization
proceeds largely by a chain-growth mechanism.
3 For examples of H-bonded macrocycles, see (a) A. J. Gallant and
M. J. MacLachlan, Angew. Chem., Int. Ed., 2003, 42, 5307;
(b) A. R. Sanford, L. Yuan, W. Feng, K. Yamato,
R. A. Flowersb and B. Gong, Chem. Commun., 2005, 4720;
(c) P. S. Shirude, E. R. Gillies, S. Ladame, F. Godde, K. Shin-Ya,
I. Huc and S. Balasubramanian, J. Am. Chem. Soc., 2007,
129, 11890; (d) J. B. Lin, X. N. Xu, X. K. Hang and Z. T. Li,
J. Org. Chem., 2008, 73, 9403; (e) E. Berni, C. Dolain,
B. Kauffmann, J.-M. Lger, C. Zhan and I. Huc, J. Org. Chem.,
2008, 73, 2687; (f) A. Petitjean, L. A. Cuccia, M. Schmutz and
J. M. Lehn, J. Org. Chem., 2008, 73, 2481; (g) Y. Y. Zhu, C. Li,
G. Y. Li, X. K. Jiang and Z. T. Li, J. Org. Chem., 2008, 73, 1745;
(h) B. Qin, X. Y. Chen, X. Fang, Y. Y. Shu, Y. K. Yip, Y. Yan,
S. Y. Pan, W. Q. Ong, C. L. Ren, H. B. Su and H. Q. Zeng, Org.
Lett., 2008, 10, 5127; (i) A. J. Helsel, A. L. Brown, K. Yamato,
W. Feng, L. H. Yuan, A. J. Clements, S. V. Harding, G. Szabo,
Z. F. Shao and B. Gong, J. Am. Chem. Soc., 2008, 130, 15784;
(j) L. Q. Yang, L. J. Zhong, K. Yamato, X. H. Zhang, W. Feng,
P. C. Deng, L. H. Yuan, X. C. Zeng and B. Gong, New J. Chem.,
2009, 33, 729; (k) B. Qin, C. L. Ren, R. J. Ye, C. Sun, K. Chiad,
X. Y. Chen, Z. Li, F. Xue, H. B. Su, G. A. Chass and H. Q. Zeng,
J. Am. Chem. Soc., 2010, 132, 9564.
BOP, a commonly used peptide coupling reagent, has often
been employed in making cyclic peptides via intramolecular
cyclizations.7b Its present use in inducing one-pot H-bonding-
assisted macrocyclizations, selectively leading to five-residue
macrocycles 1–6 from their monomeric building blocks 1a–6a,
bears no literature precedents. At the present time, we are still
totally puzzled by the fact that POCl3 and BOP only allow the
circular pentamers to be prepared from their monomeric
methoxybenzene2m–o and pyridone building blocks, respec-
tively, and that all the amide coupling conditions outlined in
Table 1 including POCl3 and BOP do not yield any circular
pyridine tetramer or fluoropentamer, respectively, built from
monomeric pyridine5c,d or fluorobenzene5e motifs. The infer-
ence is such that every type of monomer building block
destined to form the most stable circular pentamer or tetramer
requires its own unique ‘‘cognate’’ macrocyclization reagents
that seem to be ‘‘orthogonal’’ to each other and function well
only against their own specific set of ‘‘cognate’’ monomer
units. The BOP-mediated one-pot macrocyclization protocol
established here decently produces its ‘‘cognate’’ pyridone
pentamers 1–6 at yields of 10–25% in about a day, a greener
process that is far more cost-effective and time-saving than the
step-by-step lengthy synthesis, producing 2 and 6 in 1–2%
yields after months of efforts.4 This one-pot macrocyclization
protocol now enables facile access to cation-binding pentamers
with tunable exterior side chains that may promise some
interesting applications.
4 C. L. Ren, V. Maurizot, H. Q. Zhao, J. Shen, F. Zhou, W. Q. Ong,
Z. Y. Du, K. Zhang, H. B. Su and H. Q. Zeng, J. Am. Chem. Soc.,
2011, 133, 13930.
5 (a) Y. Yan, B. Qin, Y. Y. Shu, X. Y. Chen, Y. K. Yip, D. W. Zhang,
H. B. Su and H. Q. Zeng, Org. Lett., 2009, 11, 1201; (b) Y. Yan,
B. Qin, C. L. Ren, X. Y. Chen, Y. K. Yip, R. J. Ye, D. W. Zhang,
H. B. Su and H. Q. Zeng, J. Am. Chem. Soc., 2010, 132, 5869;
(c) W. Q. Ong, H. Q. Zhao, Z. Y. Du, J. Z. Y. Yeh, C. L. Ren, L. Z.
W. Tan, K. Zhang and H. Q. Zeng, Chem. Commun., 2011, 47, 6416;
(d) W. Q. Ong, H. Q. Zhao, X. Fang, S. Woen, F. Zhou, W. L. Yap,
H. B. Su, S. F. Y. Li and H. Q. Zeng, Org. Lett., 2011, 13, 3194;
(e) C. L. Ren, S. Y. Xu, J. Xu, H. Y. Chen and H. Q. Zeng, Org.
Lett., 2011, 13, 3840.
Financial support by Environment and Water Industry
Development Council and Economic Development Board
(SPORE, COY-15-EWI-RCFSA/N197-1 to H.Z.) and
National Natural Science Foundation of China (21042003 to
Z.D.) is acknowledged.
6 (a) Z. Zhang, B. Xia, C. Han, Y. Yu and F. Huang, Org. Lett., 2010,
12, 3285; (b) C. L. Ren, F. Zhou, B. Qin, R. J. Ye, S. Shen, H. B. Su
and H. Q. Zeng, Angew. Chem., Int. Ed., 2011, 50, DOI: 10.1002/
anie.201101553.
7 (a) J. L. Sessler, E. Tomat and V. M. Lynch, Chem. Commun., 2006,
4486; (b) J. S. Davies, J. Peptide Sci., 2003, 9, 471.
c
12490 Chem. Commun., 2011, 47, 12488–12490
This journal is The Royal Society of Chemistry 2011