Synthesis and structure of a bowl-like molecule by threefold metathesis reactions

Article abstract of DOI:10.1016/j.tetlet.2010.04.031

A bowl-like molecule was designed and efficiently synthesized by threefold metathesis reactions, and its structure was determined by NMR, MALDI-TOF MS spectrum, and X-ray crystallographic analysis.

Full text of DOI:10.1016/j.tetlet.2010.04.031

Tetrahedron Letters 51 (2010) 3112–3115
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and structure of a bowl-like molecule by threefold
metathesis reactions
*
Jing Cao, Zhi-Ping Song, Xiao-Zhang Zhu, Chuan-Feng Chen
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100190, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A bowl-like molecule was designed and efficiently synthesized by threefold metathesis reactions, and its
structure was determined by NMR, MALDI-TOF MS spectrum, and X-ray crystallographic analysis.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 12 March 2010
Revised 3 April 2010
Accepted 9 April 2010
Available online 13 April 2010
Keywords:
Bowl-like molecule
Threefold metathesis reactions
Synthesis
Structure
Conformationally rigid, bowl-shaped molecules are an impor-
tant class of receptors in supramolecular chemistry1 due to their
abilities to encapsulate and stabilize guest molecules, and to cata-
lyze chemical transformations within their ‘microreactor’ cage.2
However, most of the interests were focused on the construction
of calixarene and resorcin[4]arene cavitands with enforced cavities
large enough to complex with complementary organic compounds
or ions,3 and on the synthesis of aromatic molecular-bowl hydro-
carbons and their derivatives.4 So far, the synthesis of a new type
of structure connected by covalent bonds with the shape of bowl
is still a challenge in this field for chemists.
During the past 20 years, the ring-closing metathesis (RCM)
reaction has been rapidly established as an efficient approach
toward macrocyclic systems via intramolecular formation of
carbon–carbon double bonds.5 Consequently, it has found wide
applications in the synthesis of novel macrocyclic hosts6 and also
in the construction of supramolecular assemblies with specific
structures.7 However, the examples of multifold metathesis reac-
tions are still limited for their synthetic challenges.5–7
structure of a novel bowl-like molecule by threefold metathesis
reactions.
Synthesis of dibenzylamine 5 is outlined in Scheme 1. Com-
pound 2 was prepared in 86% yield by the esterification of 3-bu-
ten-1-ol 1 employing 4-methylbenzene-1-sulfonyl chloride in the
presence of Ag2O and KI. Compound 3 was synthesized by reaction
TsCl
OH
OTs
Ag2O/KI/CH2Cl2
86%
1
2
1) 4-hydroxybenzonitrile
K2CO3/CH3CN
4-hydroxybenzaldehyde
K2CO3/CH3CN
98%
2) LiAlH4/Et2O
85%
NH2
O
CHO
O
3
4
Recently, we8a reported a highly efficient approach to the syn-
thesis of a new kind of [4]pseudocatenane by threefold metathesis
reactions. According to the similar approach, we have also synthe-
sized a series of chiral [4]pseudorotaxane, and further obtained a
novel ship’s wheel-like supramolecular structure.8b Inspired by
the work reported previously, we here describe the synthesis and
1) PhMe/
2) NaBH4/MeOH
81%
O
O
N
H
5
* Corresponding author. Tel.: +86 10 62588936; fax: +86 10 62554449.
E-mail address: cchen@iccas.ac.cn (C.-F. Chen).
Scheme 1. Synthesis of the dibenzylamine 5.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.031

J. Cao et al. / Tetrahedron Letters 51 (2010) 3112–3115
3113
of 2 and 4-hydroxybenzaldehyde in the presence of K2CO3. Reac-
tion of 2 with 4-hydroxybenzonitrile, followed by reduction with
LiAlH4, gave compound 4 in 85% yield for the two steps from the
respective precursor. Finally, by the reaction of 3 and 4 in toluene,
and then by reduction with NaBH4, compound 5 was obtained in
81% yield for the two steps.
signals of 8 became more complex and indecipherable, which sug-
gested that 8 has a very rigid structure. However, when the C@O
group in 8 was reduced to methylene group, the molecular symme-
try of the product 9 was enhanced obviously. The outer aromatic
protons split into two groups, while the inner aromatic protons
move to the upfield. Moreover, the aliphatic proton signals are also
sharp and differentiable. These observations suggested the unsym-
metric structure of 8 was mainly caused by the carbonyl groups.
The MALDI-TOF mass spectrum of 8 displayed a strong peak at
m/z 1085.1 for [M+H]+. The structure of 8 was further determined
by its X-ray single crystal analysis. The single crystal of 810 suitable
for X-ray diffraction was obtained by slow evaporation of ethyl
ether to the CHCl3 solution of 8. As shown in Figure 2, the crystal
structure confirmed it as a complete macrocycle as we learned
from its 1H NMR spectrum, and it showed a bowl-like structure
with a depth of nearly 5.0 Å in the solid state. In the structure,
the adjacent phenyl rings were connected covalently through an
ethenylenedioxy bridge. As the molecule 8 was twisted by the clo-
sely arrayed atoms, the middle atomic ring lay at the bottom of the
bowl, while the ethenylenedioxy bridge was at the rim of the bowl.
Moreover, it was found that two molecules of 8 could form a
Synthesis of compound 89 is outlined in Scheme 2. Reaction of
1,3,5-benzenetricarboxylic acid with thionyl chloride gave ben-
zene-1,3,5-tricarboyl trichloride, which then reacted with 5 in
the presence of triethylamine to afford compound 6 in 90% yield
for the two steps. With the framework in hand, we further per-
formed the threefold metathesis reactions. When a solution of 6
in CH2Cl2 (2 mM) was treated with the second-generation Grubbs’
catalyst (5 mmol %), it was found that the reaction went along
smoothly and gave product 7 in 75% yield. As 7 existed as cis/trans
isomers, we further hydrogenated it by Adam’s catalyst to afford
compound 8. Moreover, we also reduced compound 8 by LiAlH4,
which gave compound 9 in 86% yield. All new compounds were
confirmed by the 1H NMR, 13C NMR, MALDI-TOF MS spectra, and
elementary analyses.9
In order to determine the structure of molecule 8, we further
compared the 1H NMR spectrum of 8 with that of compounds 6
and 9. As shown in Figure 1, the chemical shifts of the inner aro-
matic protons in 6 were in the downfield compared with those of
9 for the influence of the neighboring C@O, while the outer aro-
matic protons showed three broadened signals, which implied that
the structure of 6 is not with C3 symmetry as imagined because of
the steric hindrance although it has a free end. Compared with 6,
the 1H NMR spectrum of 8 showed that signals of terminal vinyl
protons at 5.0–6.0 ppm disappeared instead of new broadened
ones at 2.79–2.83 ppm. Moreover, due to the influence of the
closely packed atoms and the C@O groups, the aromatic proton
up-face to up-face dimer by a couple of C–HÁÁÁ
p interactions
(dC–HÁ Á Á = 2.90 Å for a), a couple of C–HÁ Á ÁO (dC–HÁ Á ÁO = 2.71 Å for
p
b) hydrogen bonding interactions, and one
p
Á Á Á
p interaction
(d = 3.23 Å for c) between the two molecules (Fig. 2c). The
pÁ Á Áp
dimers then self-assembled into a liner structure, which could fur-
ther stack into a 3D microporous architecture view along the a-axis
(Fig. 2d).
In conclusion, a bowl-like molecule has been efficiently synthe-
sized by threefold metathesis reactions, and its structure was
determined by 1H NMR, 13C NMR, MALDI-TOF MS spectrum, and
X-ray analysis. The work described here could provide a new
O
O
O
O
N
N
O
O
O
O
O
O
CO2H
O
O
(1) SOCl2
Grubbs II
N
N
N
N
(2) 5, Et3N/CH2Cl2
CH2Cl2
75%
O
HO2C
CO2H
O
90%
O
O
O
O
7
6
O
O
O
O
N
N
O
O
O
O
O
O
PtO2/H2
LiAlH4
N
N
N
N
CHCl3
96%
O
THF
86%
O
O
O
O
8
9
Scheme 2. Synthesis and reduction of the bowl-like molecule 8.

3114
J. Cao et al. / Tetrahedron Letters 51 (2010) 3112–3115
Figure 1. 1H NMR spectra of (a) 6, (b) 8 and (c) 9 (300 MHz, CDCl3).
approach to the design and synthesis of molecules with specific
structures through threefold or multifold metathesis reactions.
Acknowledgments
We thank the National Natural Science Foundation of China
(20625206), the Chinese Academy of Sciences and National Basic
Research Program of China (2009ZX09501-018) for the financial
support.
References and notes
1. (a) Cram, D. J.; Choi, H. J.; Bryant, J. A.; Knobler, C. B. J. Am. Chem. Soc. 1992, 114,
7748–7765; (b) Schramm, M. P.; Hooley, R. J.; Rebek, J., Jr. J. Am. Chem. Soc.
2007, 129, 9773–9779; (c) Hooley, R. J.; Van Anda, H. J.; Rebek, J., Jr. J. Am. Chem.
Soc. 2007, 129, 13464–13473; (d) Choi, H. J.; Nguyen, Q. T.; Park, Y. S.; Choi, C.
H.; Paek, K.; Kim, E. H. Chem. Commun. 2009, 4971–4973; (e) Crisóstomo, F. R.
P.; Lledó, A.; Shenoy, S. R.; Iwasawa, T.; Rebek, J., Jr. J. Am. Chem. Soc. 2009, 131,
7402–7410.
2. (a) Hogberg, G. S. J. Am. Chem. Soc. 1980, 102, 6046–6050; (b) Purse, B. W.;
Rebek, J. Proc. Natl. Acad. Sci. 2005, 102, 10776–10777; (c) Fox, O. D.; Cookson,
J.; Wilkinson, E. J. S.; Drew, M. G. B.; MacLean, E. J.; Teat, S. J.; Beer, P. D. J. Am.
Chem. Soc. 2006, 128, 6990–7002; (d) Kawase, T.; Kurata, H. Chem. Rev. 2006,
106, 5250–5273; (e) Park, S. J.; Kwon, O. H.; Lee, K. S.; Yamaguchi, K.; Jang, D. J.;
Hong, J. I. Chem. Eur. J. 2008, 14, 5353–5359.
3. Some recent examples, see: (a) Roberta, P.; Suman, M.; Dalcanale, E. Eur. J. Org.
Chem. 2004, 451–462; (b) Ihm, C.; In, Y.; Park, Y.; Paek, K. Org. Lett. 2004, 6,
369–372; (c) Xiao, S. X.; Ajami, D.; Rebek, J., Jr. Org. Lett. 2009, 11, 3163–3165.
4. Some recent examples, see: (a) Wu, Y. T.; Siegel, J. S. Chem. Rev. 2006, 106,
4843–4867; (b) Qin, B.; Chen, X. Y.; Fang, X.; Shu, Y. Y.; Yip, Y. K.; Yan, Y.; Pan, S.
Y.; Ong, W. Q.; Ren, C. L.; Su, H. B.; Zeng, H. Q. Org. Lett. 2008, 10, 5127–5130; (c)
Nishida, S.; Morita, Y.; Ueda, A.; Kobayashi, T.; Fukui, K.; Ogasawara, K.; Sato,
K.; Takui, T.; Nakasuji, K. J. Am. Chem. Soc. 2008, 130, 14954–14955; (d) Wang,
K. K.; Wang, Y. H.; Yang, H.; Akhmedov, N. G.; Petersen, J. L. Org. Lett. 2009, 11,
2527–2530.
5. (a) Chuchuryukin, A. V.; Dijkstra, H. P.; Suijkerbuijk, B. M. J. M.; Gebbink, R. J.
M.; van Klink, G. P. M.; Mills, A. M.; Spek, A. L.; van Koten, G. Angew. Chem., Int.
Ed. 2003, 42, 228–230; (b) Chuchuryukin, A. V.; Chase, P. A.; Dijkstra, H. P.;
Suijkerbuijk, B. M. J. M.; Mills, A. M.; Spek, A. L.; van Klink, G. P. M.; van Koten,
G. Adv. Synth. Catal. 2005, 347, 447–462; (c) Song, K. H.; Kang, S. O.; Ko, J. Chem.
Eur. J. 2007, 13, 5129–5134; (d) Constable, E. C.; Housecroft, C. E.; Neuburger,
M.; Rösel, P. J.; Schaffner, S.; Zampese, J. A. Chem. Eur. J. 2009, 15, 11746–11757.
6. (a) Kerckhoffs, J. M. C. A.; ten Cate, M. G. J.; Mateos-Timoneda, M. A.; van
Leeuwen, F. W. B.; Snellink-Ruël, B.; Spek, A. L.; Kooijman, H.; Crego-Calama,
M.; Reinhoudt, D. N. J. Am. Chem. Soc. 2005, 127, 12697–12708; (b) Parulekar, S.
N.; Muppalla, K.; Fronczek, F. R.; Bisht, K. S. Chem. Commun. 2007, 4901–4903;
(c) Rudzevich, Y.; Cao, Y. D.; Rudzevich, V.; Böhmer, V. Chem. Eur. J. 2008, 14,
3346–3354; (d) Bogdan, A.; Bolte, M.; Böhmer, V. Chem. Eur. J. 2008, 14, 8514–
8520.
Figure 2. (a) Top view and (b) side view of crystal structure of 8. (c) View of a
dimer, blue lines denote the noncovalent interactions. (d) Packing of 8 viewed along
the a-axis. Hydrogen atoms not involved in the interactions are omitted for clarity.
7. Some recent examples, see: (a) Badjic, J. D.; cantrill, S. J.; Stoddart, J. F. Angew.
Chem., Int. Ed. 2004, 43, 3273–3278; (b) Molokanova, O.; Vysotsky, M. O.; Cao,

J. Cao et al. / Tetrahedron Letters 51 (2010) 3112–3115
3115
Y. D.; Thondorf, I.; Böhmer, V. Angew. Chem., Int. Ed. 2006, 45, 8051–8055; (c)
Hiraoka, S.; Yamauchi, Y.; Arakane, R.; Shionoya, M. J. Am. Chem. Soc. 2009, 131,
11646–11647.
[M+K]+. IR: 2929 (C–H), 1643 cmÀ1 (C@O). Compound 8. A mixture of 7
m
(54 mg, 0.05 mmol) and PtO2 (5 mg) in chloroform (20 mL) was stirred under
H2 atmosphere for 3 h. After the mixture was filtrated and the filtrate was then
concentrated, 52 mg (96%) of 8 was obtained as a white solid. Mp: 138–140 °C.
1H NMR (300 MHz, CDCl3): d 1.59 (br s, 12H), 1.81 (br s, 12H), 3.94–4.29 (brm,
24H), 6.60–7.88 (br s, 27H). 13C NMR (300 MHz, CDCl3): d 24.5, 25.2, 27.4, 28.4,
29.7, 45.7, 47.6, 51.1, 51.6, 67.7, 67.9, 115.0, 115.2, 115.5, 123.4, 125.8, 126.7,
127.6, 127.9, 128.4, 128.8, 129.3, 130.0, 137.0, 137.5, 138.5, 158.3, 158.9, 169.8,
170.1. MALDI-TOF MS: m/z 1090.5 [M+H]+, 1112.5 [M+Na]+, 1128.4 [M+K]+. IR:
8. (a) Zhu, X.-Z.; Chen, C.-F. J. Am. Chem. Soc. 2005, 127, 13158–13159; (b) Zhu, X.-
Z.; Chen, C.-F. Chem. Eur. J. 2006, 12, 5603–5609.
9. Compound 6. The solution of 1,3,5-benzenetricarboxylic acid (105 mg,
0.5 mmol) in thionyl chloride (10 mL) was refluxed for 4 h to afford
a
colorless solution, which was concentrated under reduced pressure, and the
residue was dried in vacuo to yield benzene-1,3,5-tricarboyl trichloride. To the
trichloride in dry dichloromethane (30 mL) was then added
5
(506 mg,
m
2927 (C–H), 1644 (C@O) cmÀ1. Anal. Calcd for C69H75N3O9ÁH2O: C, 74.77; H,
1.5 mmol) and triethylamine (0.84 mL, 606 mg, 6 mmol). After the mixture
was stirred in room temperature for an hour, the solvent was removed under
reduced pressure, and the crude product was purified by column
chromatography over silica gel (eluent: CH2Cl2/methanol = 80:1) to afford 6
(520 mg) in 90% yield as a white solid. Mp: 113–115 °C. 1H NMR (300 MHz,
CDCl3): d 2.56 (br s, 12H), 3.87–4.03 (m, 12H), 4.13 (s, 6H), 4.53 (s, 6H), 5.11–
5.22 (m, 12H), 5.85–5.99 (m, 6H), 6.79 (br s, 6H), 6.88 (br s, 12H), 7.17 (br s,
6H), 7.60 ppm (s, 3H). 13C NMR (300 MHz, CDCl3): d 33.7, 46.3, 50.8, 67.3, 76.7,
77.1, 77.3, 77.6, 114.9, 117.1, 126.2, 127.6, 128.3, 128.5, 129.8, 134.4, 137.2,
158.5, 170.1. MALDI-TOF MS: m/z 1169.0 [M+H]+, 1191.0 [M+Na]+, 1206.9
7.00; N 3.79. Found: C, 74.89; H, 7.00; N, 3.60. Compound 9. To a solution of 8
(76 mg, 0.07 mmol) in anhydrous THF (20 mL) was added LiAlH4 (0.14 g,
3.7 mmol) in small portions. After being refluxed for 6 h, the reaction mixture
was quenched with water and then extracted with dichloromethane. The
organic layer was dried over anhydrous sodium sulfate. The solvent was
evaporated off to afford 9 (63 mg) in 86% yield as a white solid. Mp: 78–80 °C.
1H NMR (300 MHz, CDCl3): d 1.43–1.56 (m, 12H), 1.76–1.80 (m, 12H), 3.48 (s,
9H), 3.61 (s, 9H), 4.00 (t, 12H), 6.79 (d, 9H), 7.17 (s, 3H), 7.21 (d, 9H). 13C NMR
(300 MHz, CDCl3): d 24.6, 28.1, 56.1, 56.5, 67.8, 114.7, 128.5, 130.3, 131.0,
139.2, 158.0. MALDI-TOF MS: m/z 1048.8 [M+H]+. IR:
m
2935 (C–H) cmÀ1. Anal.
[M+K]+. IR:
m
1632 cmÀ1 (C@O). Anal. Calcd for C75H81N3O9Á1/2H2O: C, 76.50; H,
Calcd for C69H81N3O6ÁH2O: C, 77.71; H, 7.84; N, 3.94. Found: C, 77.65; H, 7.82;
7.02; N, 3.57. Found: C, 76.43; H, 7.00; N, 3.73. Compound 7. A solution of 6
(117 mg, 0.10 mmol) in anhydrous CH2Cl2 (50 mL) was stirred under Ar for a
few minutes, Grubbs’ II catalyst (4 mg, 0.005 mmol) was then added. After the
solution was purged with Ar for 10 min, it was further refluxed for a day under
Ar. The solvent was evaporated off under reduced pressure and the crude
product was subjected to column chromatography over silica gel with CH2Cl2/
CH3OH (60:1) as the eluent to yield 81 mg 7 (75%) as a white solid. 1H NMR
(300 MHz, CDCl3): d 2.45 (br s, 12H), 4.01 (brm, 24H), 5.66 (s, 6H), 6.60–7.88
(brm, 27H). MALDI-TOF MS: m/z 1085.1 [M+H]+, 1107.1 [M+Na]+, 1123.1
N, 3.92.
10. Crystal data for 8: C69H75N3O9, Mw = 1090.32, crystal size: 0.34 Â 0.32 Â
0.24 mm3, crystal system: monoclinic, space group:
P 1 21/a 1, a =
10.810(5) Å, b = 39.197(17) Å, c = 15.994(7) Å, b = 92.382(4)°, U = 6771(5) Å3,
Z = 4, T = 113(2) K, 11911 reflections measured, 9130 unique (Rint = 0.0649),
R1 = 0.0733, wR2 = 0.1716. CCDC 767880 contains the supplementary
crystallographic data for 8. The data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk.