Synthesis and structure of an air-stable binuclear complex of bis(ethylcyclopentadienyl)zirconium perfluorooctanesulfonate and its catalytic application in one-pot three-component aza-Friedel-Crafts reactions

Article abstract of DOI:10.1016/j.tetlet.2013.10.131

An air-stable Lewis acidic binuclear complex of bis(ethylcyclopentadienyl) zirconium perfluorooctanesulfonate (1a) was successfully synthesized by the reaction of (CH₃CH₂Cp)₂ZrCl₂ with C₈F₁₇

Full text of DOI:10.1016/j.tetlet.2013.10.131

Tetrahedron Letters 55 (2014) 120–123
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and structure of an air-stable binuclear complex
of bis(ethylcyclopentadienyl)zirconium perfluorooctanesulfonate
and its catalytic application in one-pot three-component
aza-Friedel–Crafts reactions
a
a,
Xiaohong Zhang a,b, Xingsong Zhang b, Ningbo Li a, Xinhua Xu a, , Renhua Qiu , Shuangfeng Yin
⇑
⇑
a College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
b College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
a r t i c l e i n f o
a b s t r a c t
Article history:
An air-stable Lewis acidic binuclear complex of bis(ethylcyclopentadienyl)zirconium perfluorooctane-
sulfonate (1a) was successfully synthesized by the reaction of (CH3CH2Cp)2ZrCl2 with C8F17SO3Ag. The
complex 1a was characterized by different techniques and found to have the nature of air-stability, water
tolerance, thermal-stability, and strong Lewis-acidity. In addition, its solubility was higher than that of
our previously reported uninuclear zirconocene bis(perfluorooctanesulfonate). This complex showed
high catalytic efficiency, good recyclability, and reusability in the one-pot three-component aza-Fri-
edel–Crafts reactions of indoles with aldehydes and N,N-dimethylaniline. The yields of the corresponding
3-diarylmethyl indoles are higher than those from the traditional Lewis acidic catalysts.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 11 August 2013
Revised 16 October 2013
Accepted 28 October 2013
Available online 5 November 2013
Keywords:
Bis(ethylcyclopentadienyl)zirconium
Perfluorooctanesulfonate
Lewis acid
Aza-Friedel–Crafts reaction
Introduction
M = Zr, Ti, Hf) were successfully applied to catalyze various C–C
bond forming reactions.13 Unfortunately, the application of these
Indoles are an important class of heterocycles that are found
widely in many natural products.1 Many natural and synthetic in-
doles are found to exhibit a broad range of biological activities,
including anticancer,2 antiangiogenic,3 antiplasmodial,4 and anti-
tumor activites.5 Consequently, the synthesis of indole derivatives
have attracted great attention in organic chemistry over 50 years.6
Among the various synthetic strategies, Lewis-acids catalyzed car-
bon–carbon bond forming reactions are of great importance. For
example, the C3-alkylation of indoles with various reagents using
InCl3 (In(OTf)3),7 Sc(OTf)3,8 FeCl3,9 CeCl3,10 or Al(OTf)311 as catalysts
were continuously reported. However, most of them have one or
more disadvantages such as air- or moisture-sensitive and the
need of strictly anhydrous reaction conditions. Furthermore, most
of these catalysts cannot be recycled owing to their decomposition
or deactivation with the water generated in-situ. Therefore, it is
still desirable to look for some air-stable, water-tolerant, strongly
Lewis-acidic, and recyclable catalysts instead of the traditional Le-
wis-acid catalysts.
metallocene triflates was limited greatly owing to their facile
hydrolysis and unstable features.14 To overcome these shortcom-
ings, Otera and co-workers found that the incorporation of perfluo-
roalkyl(aryl)sulfonate moieties into organometallic (ie., Sn, Zr, and
Ti) cations could enhance acidity and stability.15 With such under-
standing, several air-stable metallocene complexes bearing per-
fluorooctanesulfonate groups (Cp2M(OSO2C8F17)2, M = Ti, Zr) and
[{CpHf(OH2)3}2(l ] were synthesized succes-
2-OH)2][OSO2C8F17 4
sively in our group and were confirmed to show strong Lewis acid-
ity and high catalytic activity in the C–C and C–O bond forming
reactions.16 However, their relatively low solubility in organic sol-
vents owing to the strong lipophobic nature of C8F17 group maybe
declines the catalytic efficiency. We envisioned that alkyl group
incorporated with Cp ring will maybe increase the solubility as
well as the catalytic efficiency. Based on this idea and as part of
our ongoing efforts devoted to metallocene complexes, ethyl was
incorporated with cyclopentadiene group to afford an air-stable
Lewis-acidic organometallic species. In this Letter, we wish to re-
Recently, cationic group metallocene compounds have attracted
increasing attention.12 The metallocene triflates complexes of
titanium, zirconium, and hafnocene (Cp2M(OTf)2, Cp = C5H5;
port the synthesis and characterization of
binuclear complex [{CH3CH2CpZr(OH2)3}2(
l
2-hydroxy bridged
l
2-OH)2][OSO2C8F17 4-
]
Á4H2OÁ2THF (denoted as 1aÁ4H2OÁ2THF hereafter) and its catalytic
application in the one-pot three-component aza-Friedel–Crafts
reactions of indoles, aldehydes, and N,N-dimethylaniline.
⇑
Corresponding authors. Fax: +86 731 88821546.
E-mail addresses: xhx1581@hnu.edu.cn (X. Xu), sf_yin@hnu.edu.cn (S. Yin).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.10.131

X. Zhang et al. / Tetrahedron Letters 55 (2014) 120–123
121
Results and discussion
The synthesis of 1a is shown in Scheme 1.17 Treatment of
bis(ethylcyclopentadienyl)zirconium dichloride [(CH3CH2Cp)2-
ZrCl2] (1 equiv) with silver perfluorooctanesulfonate (AgOSO2C8-
F17)
(2 equiv) in dry THF yielded 1aÁxH2OÁyTHF (after
recrystallization from THF). The water molecules in the complex
originated from air or the solvent, and the hydrate numbers x
and solvating ligand THF y varied according to the reaction condi-
tions. The result of 1H NMR spectroscopy (in dry [D6] acetone)
showed that in the freshly prepared sample after recrystallization
and vacuum treatment at 60 °C for 1 h, complex 1aÁxH2OÁyTHF be-
came 1a (x = 0, y = 0). It is notable that the samples remained as dry
powder after being kept in open air over a month, and exhibited no
sign of structural change by 1H NMR spectroscopy analysis, show-
ing a great advantage over zirconocene bis(triflate) and the tradi-
tional Lewis-acid catalysts from an operational point of view.
Though it is difficult to acquire the crystal structure owing to
the large disorder of perfluorooctanesulfonate group, the cationic
structure of 1aÁ4H2OÁ2THF was fortunately confirmed by X-ray
analysis after a series of efforts. The crystals suitable for the X-
ray diffraction were obtained by diffusion of hexane into saturated
THF solution. The crystal structure together with selected bonds
and angles are shown in Figure 1. It is clear that bis(ethyl) zircono-
cene in compound 1a is cationic. Also, it is interesting to find that
complex 1a is binuclear structure, different from the uninuclear
Figure 1. Crystal structure of [CH3CH2CpZr(OH2)3}2(
l
2-OH)2][OSO2C8F17]4Á4H2-
OÁ2THF] (1aÁ4H2OÁ2THF), Hydrogen atoms are omitted for clarity. Selected bond
distances (Å) and angles (°): Zr(1)–O(8), 2.110(5); Zr(1)–O(11), 2.130(5); Zr(1)–
O(8A), 2.170(5); Zr(1)–O(10), 2.194(5); Zr(1)–O(9), 2.202(5); Zr(1)–C(3), 2.505(8);
Zr(1)–C(4), 2.521(7); Zr(1)–Zr(1A), 3.5315(15); O(8)–Zr(1)–O(11), 94.8(2); O(8)–
Zr(1)–O(8A), 68.8(2); O(8)–Zr(1)–O(10), 150.8(2); O(10)–Zr(1)–O(9), 80.1(2); O(8)–
Zr(1)–C(3), 99.6(2); O(10)–Zr(1)–C(2), 131.0(2); C(2)–Zr(1)–C(4), 54.0(3); O(8)–
Zr(1)–Zr(1A), 34.96(13); C(5)–Zr(1)–Zr(1A), 153.99(19); Zr(1)–O(8)–Zr(1A),
111.2(2); The planes of the two Cp rings are parallel.
a relatively strong acidity with acid strength of 0.8 < H0 < 3.3 (H0
being the Hammett acidity function, see ESI), the same as that of
Cp2Zr(OSO2C8F17)2.16e Accordingly, these features of complex 1a
encouraged us to evaluate its performance as Lewis acid catalyst
in the one-pot three-component aza-Friedel–Crafts reactions of
indoles with aldehydes and tertiary aromatic amines. The reactions
generated the corresponding 3-diarylmethyl indoles in moderate
to good yields (Scheme 2).
structure of Cp2Zr(OSO2C8F17)2
16d even though their synthetic pro-
cedures are identical. And the zirconium atoms have a distorted
octahedral coordination with the Cp group trans to the OH unit,
We choose to study the three-component reaction of indole
with benzaldehyde and N,N-dimethylaniline as a model reaction
to determine the optimal reaction conditions (Table 1).19 In view
of the binuclear structure, 2.5 mol % 1a was used as catalyst.
Firstly, different solvents were screened at 100 °C to find that
ClCH2CH2Cl was the most effective solvent, giving the correspond-
ing product in 75% yield (entries 1–5). The yield was superior to
similar to that of [{CpZr(OH2)3}2(
l
2-OH)2] [C6F5SO3]4Á6H2O.18
The Zr–O distances of 1aÁ4H2OÁ2THF are 2.110(5), 2.130(5),
2.170(5), 2.194(5), and 2.202(5) Å, respectively. The Zr(2)–O(16)–
Zr(1) angle is 111.2(2)° and the Zr–Zr distance is 3.5315(15), show-
À
ing that there is no Zr–Zr interaction. The C8F17SO3 ions, the dis-
sociated H2O molecules, and the solvating ligand THF are packed
around the complex cation in such a way that their oxygen atoms
point toward the H2O ligands. The C8F17 chains of the anion, on the
other hand, are clustered together to produce hydrophobic do-
mains in the crystal structure.
The thermal behavior of complex 1a was investigated by ther-
mogravimetric-differential scanning calorimetry (TG-DSC) in air
(Fig. S1, see ESI). The TV-DSC curves indicate three stages of weight
losses. The endothermic step below 100 °C can be attributed to the
removal of water molecules. The material is stable up to about
250 °C, after which weight loss of exothermic nature emerges, pos-
sibly resulting from the oxidation of organic entities. The removal
of perfluorooctanesulfuryl ligand at about 400 °C was observed,
thus leaving zirconium dichloride compounds. Conductivity
measurement was applied to investigate their ionic dissociation
behavior in CH3CN (Table S1, see ESI). The molar conductivity
that of FeCl3,20 its counterpart 5 mol % Cp2Zr(OSO2C8F17 2
and
)
[{CpZr(OH2)3}2(
l
2-OH)2] [C6F5SO3]4Á6H2O (entry 4). When the
reaction temperature and time were decreased to 80 °C and 12 h,
the yields were sharply decreased to 50% and 44%, respectively
(entries 4 and 6), demonstrating that the reaction temperature
and time were important to this system. Controlled experiments
showed that no product can be obtained in the absence of 1a (entry
7) and no obvious improvement of the yield was observed by
increasing the catalyst loading to 5.0 mol % (entry 8).
Subsequently, the scope of indoles and benzaldehydes for the
three-component aza-Friedel–Crafts reactions using 1a as catalyst
was evaluated (Table 2). It was found that indoles bearing electron-
donating groups, such as methyl and methoxyl (entries 2, 3, 9 and
10), showed slightly higher reactivity than those with electron-
withdrawing groups, like F, Cl, and Br (entries 4–6 and 8). It is
worth to note that no reaction was observed when 5-nitroindole
(bearing the strong electron-withdrawing group) was employed
as the substrate (entry 7). On the contrary, benzaldehydes bearing
electron-withdrawing groups (NO2, CN, Cl, entries 13–15) gave
(
K
) of 1aÁ4H2OÁ2THF) is 670
l
S cmÀ1 in CH3CN (1.0 mmol LÀ1) at
25 °C. The large molar conductivity value is consistent with com-
plete ionization into 1:4 electrolyte in CH3CN, implying that these
complexes are cationic in the solid state and in solution. Actually,
owing to the existence of ethyl, it is more soluble in some polar
organic solvents such as acetone, CH3CN, THF, EtOAc, and MeOH
(Table S2, see ESI) than the Cp2Zr(OSO2C8F17)2.16e Notably, it has
N
CHO
N
H
N
R2
1a
(2.5 mol%)
CH2ClCH2Cl, 100 oC, 24 h
R1
+
+
OH
H2O
2 equiv
2 H
R1
OH2
Zr
O
AgOSO C F
O
Cl
Cl
2
8
17
R2
Zr
Zr
• O S C8F17
O
•
4H2O•2THF
4
N
H
THF, rt.,
O
2 h, Dark
H
H2O
OH
H2O
2
Scheme 2. The aza-Friedel–Crafts reactions of indoles with aldehydes and N,N-
dimethylaniline catalyzed by complex 1a.
Scheme 1. Synthesis of 1aÁ4H2OÁ2THF.

122
X. Zhang et al. / Tetrahedron Letters 55 (2014) 120–123
Table 1
Screening optimal conditionsa
N
CHO
N
H
N
1a
solvent
+
+
N
H
Entry
Solvent
1a (mol %)
Temp (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
THF
DMSO
CH3CN
ClCH2CH2Cl
Toluene
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
2.5
2.5
2.5
2.5
2.5
2.5
—
100
100
100
100
100
80
46
35
24
75 (44c, 70d, 66e)
Trace
50
0
100
100
5
76
Figure 2. The X-ray crystal structure of compound 5k.
a
Indole (0.5 mmol), benzaldehyde (0.55 mmol) and N,N-dimethylaniline
(0.55 mmol), solvent (2 mL), 24 h.
b
Isolated yields.
The reaction time was shorten to 12 h.
Using 5 mol % Cp2Zr(OSO2C8F17
Using [{CpZr(OH2)3}2(
c
[Zr]
d
) as catalyst.
2
H
e
l
2-OH)2]Á[C6F5SO3]4Á6H2O as catalyst.
O
Ar
+H+
-H2O
..
N
+
Ar
N
N
+
+
H
A
N
Ar
Table 2
N
Ar
Aza-Friedel–Crafts of indoles with aldehydes and N,N-dimethylaniline catalyzed by
complex 1aa
H
N
+
H
N
N
H
CHO
N
H
N
R2
Scheme 3. Plausible mechanism of the three-component aza-Friedel–Crafts reac-
tion catalyzed by 1a.
1a
(2.5 mol%)
CH2ClCH2Cl, 100 oC, 24 h
R1
+
+
R1
R2
5
N
H
2
3
4a
Table 3
Entry
R1
H(2a)
5-CH3(2b)
5-OCH3(2c)
5-F(2d)
5-Cl(2e)
5-Br(2f)
5-NO2(2g)
6-F(2h)
7-CH3(2i)
2-CH3(2j)
H(2a)
R2
Product
Yieldb
Yield of the one-pot three-component aza-Friedel–Crafts reactions catalyzed by
recovered 1aa
1
2
3
4
5
6
7
8
H(3a)
H(3a)
H(3a)
H(3a)
H(3a)
H(3a)
H(3a)
H(3a)
5a
5b
5c
5d
5e
5f
75
77
80
64
65
66
—
63
68
69
70
68
78
74
78
56
71
82
50
66
Entry of cycle
1
2
3
4
5
Yieldb (%)
Cat.c (%)
75
83
72
82
71
80
73
81
72
80
a
Indole (0.5 mmol), benzaldehyde (0.55 mmol) and N,N-dimethylaniline
—
(0.55 mmol), catalyst 1a (28.5 mg, 2.5 mol %), solvent (2 mL), 24 h.
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
5s
b
Isolated yield.
Isolated yield of recovered catalyst.
9
H(3a)
H(3a)
c
10
11
12
13
14
15
16
17
18
19
20
4-CH3(3b)
4-OCH3(3c)
4-NO2(3d)
4-CN(3e)
2,4-DiCl(3f)
2-Naphthyl(3g)
4-OCH3(3c)
4-NO2(3d)
4-OCH3(3c)
4-NO2(3d)
H(2a)
H(2a)
H(2a)
H(2a)
aldehyde is increased. Based on the results of electronic effects of
indoles and benzaldehydes, treatment of 5-methoxylindole with
4-methoxybenzaldehyde and 4-nitrobenzaldehyde afforded com-
pounds 5p, 5q in 71%, 82% yields, respectively (entries 17 and
18). Meanwhile, 5-fluoroindole reacted with 4-methoxybenzalde-
hyde and 4-nitrobenzaldehyde, giving 5r, 5s in 50%, 66% yields,
respectively (entries 19 and 20).
H(2a)
5-OCH3(2c)
5-OCH3(2c)
5-F(2d)
5-F(2d)
a
According to the reported findings,16b,e,20 the proposed mecha-
nism of the three-component aza-Friedel–Crafts reaction of indole
with benzaldehyde and N,N-dimethylaniline is shown in Scheme 3.
When solid 1a was added to the reaction system, the ligand OH
groups dissociate immediately from the bis(ethyl) zirconocene
cation. At this stage, there is frequent intra- and intermolecular
exchange of substrate and organic solvent. The carbonyl group
coordinates with the zirconium atoms and was activated. Then
the activated benzaldehyde reacted with N,N-dimethylaniline to
give an intermediate A. The b-carbon of the indole attacks the
intermediate to produce the aimed product.
Indole (0.5 mmol), benzaldehyde (0.55 mmol) and N,N-dimethylaniline
(0.55 mmol), catalyst 1a (28.5 mg, 2.5 mol %), solvent (2 mL), 24 h.
b
Isolated yields.
their corresponding products in higher yields than those with elec-
tron-donating groups (entries 11 and12). The structure of com-
pound 5k was confirmed by X-ray crystallography (Fig. 2).
Gratifyingly, 2-naphthaldehyde was also tolerated in this process,
providing the compound 5o in 56% yield (entry 16), demonstrating
that the metallocene complex 1a catalyzed-aza-Friedel–Crafts
reaction is possible even in case where steric hindrance from the

X. Zhang et al. / Tetrahedron Letters 55 (2014) 120–123
123
6. (a) Shirakawa, S.; Kobayashi, S. Org. Lett. 2006, 8, 4939; (b) Lang, R.; Shi, L.; Li,
D.; Xia, C.; Li, F. Org. Lett. 2012, 14, 4130; (c) Ramesh, C.; Lei, P.-M.; Janreddy, D.;
Kavala, V.; Kuo, C.-W.; Yao, C.-F. J. Org. Chem. 2012, 77, 8451; (d) Jones, C. D. J.
Org. Chem. 1972, 37, 3624; (e) Tokunaga, M.; Ota, M.; Haga, M.-A.; Wakatsuki,
Y. Tetrahedron Lett. 2001, 42, 3865.
7. Nagarajan, R.; Perumal, P. T. Tetrahedron 2002, 58, 1229.
8. Yadav, J. S.; Reddy, B. V. S.; Rao, K. V. R.; Kumar, G. G. K. S. N. Tetrahedron Lett.
2007, 48, 5573.
To test the reusability of the catalyst and the reproducibility of
catalytic performance, 1a was subjected to recycle in the
three-component reaction of indole with benzaldehyde and N,N-
dimethylaniline (Table 3). The detected change in product yield
was minimal in a trial of five cycles, demonstrating that the
catalyst is stable and suitable for reuse.
9. (a) Jana, U.; Maiti, S.; Biswas, S. Tetrahedron Lett. 2007, 48, 7160; (b) Yadav, J. S.;
Reddy, B. V. S.; Praneeth, K. Tetrahedron Lett. 2008, 49, 199; (c) Yadav, J. S.;
Reddy, B. V. S.; Narasimhulu, G.; Reddy, N. S.; Reddy, P. N.; Purnima, K. V.;
Naresh, P.; Jagadeesh, B. Tetrahedron Lett. 2010, 51, 244.
Conclusions
10. (a) Yadav, J. S.; Reddy, B. V. S.; Chandrakanth, D.; Satheesh, G. Tetrahedron Lett.
2007, 48, 8040; (b) Silveira, C. C.; Mendes, S. R.; Wolf, L.; Martins, G. M.
Tetrahedron Lett. 2010, 51, 4560.
11. Gohain, M.; Marais, C.; Bezuidenhoudt, B. C. B. Tetrahedron Lett. 2012, 53, 4704.
12. Suzuki, K.; Hintermann, L.; Yamanoi, S. In Titanium and Zirconium in Organic
Synthesis; Marek, I., Ed.; Wiley: Weinheim, 2002; p 282.
13. (a) Hollis, T. K.; Bosnich, B. J. Am. Chem. Soc. 1995, 117, 4570; (b) Hollis, T. K.;
Robison, N. P.; Bosnich, B. J. Am. Chem. Soc. 1993, 114, 5464.
14. Hollis, T. K.; Robison, N. P.; Bosnich, B. Tetrahedron Lett. 1992, 33, 6423.
15. (a) An, D. L.; Peng, Z. H.; Orita, A.; Kurita, A.; Man-e, S.; Ohkubo, K.; Li, X. S.;
Fukuzumi, S.; Otera, J. Chem. Eur. J. 2006, 12, 1642; (b) Li, X. S.; Kurita, A.; Man-
e, S.; Orita, A.; Otera, J. Organometallics 2005, 24, 2567.
In conclusion, for the first time the novel air-stable Lewis
acidic complex of [{CH3CH2CpZr(OH2)3}2(l ]
2-OH)2][OSO2C8F17
4-
Á4H2 OÁ2 THF has been synthesized and its structure was deter-
mined by single-crystal X-ray. The complex was characterized
by various techniques such as TG-DSC analysis, conductivity mea-
surement, and acid strength (H0). It can be used as an excellent
catalyst for the three-component reactions of indoles with benz-
aldehydes and N,N-dimethylanilines. The novel complex has the
advantages of air-stability, water tolerance, thermal-stability,
highly catalytic efficiency, and reusability with better solubility
and competitive yields as compared to its counterparts, such as
Cp2Zr(OSO2C8F17)2Á 3H2OÁTHF and the traditional Lewis-acid
catalysts.
16. (a) Qiu, R. H.; Zhu, Y. Y.; Xu, X. H.; Li, Y. H.; Shao, L. L.; Ren, X. F.; Cai, X. T.; An, D. L.;
Yin, S. F. Catal. Commun. 2009, 10, 1889; (b) Qiu, R. H.; Zhang, G. P.; Zhu, Y. Y.; Xu,
X. H.; Shao, L. L.; Li, Y. H.; An, D. L.; Yin, S. F. Chem. Eur. J. 2009, 15, 6488; (c) Qiu, R.
H.; Zhang, G. P.; Ren, X. F.; Xu, X. H.; Yang, R. H.; Luo, S. L.; Yin, S. F. J. Organomet.
Chem. 2009, 695, 1182; (d) Qiu, R. H.; Zhang, G. P.; Xu, X. H.; Zou, K. B.; Shao, L. L.;
Fang, D. W.; Li, Y. H.; Orita, A.; Saijo, R.; Mineyama, H.; Suenobu, T.; Fukuzumi, S.;
An, D. L.; Otera, J. J. Organomet. Chem. 2009, 694, 1524; (e) Qiu, R. H.; Xu, X. H.;
Peng, L. F.; Zhao, Y. L.; Li, N. B.; Yin, S. F. Chem. Eur. J. 2012, 18, 6172.
17. Synthesis of complex 1a: To a solution of (CH3CH2Cp)2ZrCl2 (174 mg, 0.5 mmol)
in 5 mL THF was added a solution of AgOSO2C8F17 (605 mg, 1 mmol) in 10 mL
THF. After the mixture was stirred at 25 °C for 12 h in the absence of light, it
was filtrated. The filtrate was added into acetone and placed in a small jar and
then put into a larger jar which was added 20 mL dry hexane and then the
larger jar was obdurate. After keeping in the refrigerator for 24 h, the white
crystal was obtained (445 mg, 70%). mp 166–167 °C. 1H NMR (400 MHz, [D6]
acetone) d = 6.61–6.60 (m, 8H, Cp), 2.69 (q, 4H, J = 7.5 Hz), 1.15 (t, 6H,
J = 7.6 Hz); 19F NMR (288 MHz, [D6] acetone): À76.07 to À76.12 (m, 3F,
CF3À), À109.38 to 109.41 (m, 2F, –CF2À), À115.50 to À115.55 (m, 2F, –CF2À),
À116.61 to À116.90 (m, 6F, –CF2À), À117.73 to À117.75 (m, 2F, –CF2À),
À121.17 to À121.24 (m, 2F, –CF2À). Crystallographic data for [{CH3CH2
Acknowledgments
The authors thank the National Natural Science Foundation of
China (Nos. 21172061 and 21273068), the NSF of Hunan Province
(10JJ1003, 11JJ5009), and the Fundamental Research Funds for the
Central Universities, Hunan university, for financial support.
Supplementary data
Supplementary data (CCDC 951169 and 951170 contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from the cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/ata_request/cif) associated
with this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.tetlet.2013.10.131.
CpZr(OH2)3}2(
l
2-OH)2][OSO2C8F17]4Á4H2OÁ2THF: C54H56F68O26S4Zr2, white
prism, formula weight 2723.66, Triclinic, P À 1, a = 10.498(2) Å, b = 10.
929(2) Å, c = 20.659(4) Å, V = 2277.4(8) Å3, Z = 2, Dcalcd = 1.986 g cmÀ3, R(int)
0.0631, R1 = 0.0911, wR2 = 0.2266, GOF = 1.005, CCDC no. 951169.
=
18. Qiu, R. H.; Xu, X. H.; Li, Y. H.; Zhang, G. P.; Shao, L. L.; An, D. L. Chem. Commun.
2009, 1679.
19. Typical procedure for the aza-Friedel–Crafts of indoles with aldehydes and N,N-
dimethylaniline catalyzed by complex 1a: To a 10 mL sealed tube was added
indole (0.5 mmol), 4-methoxybenzaldehyde (0.55 mmol) and N,N-
dimethylaniline (0.55 mmol), CH2ClCH2Cl (2 mL) and catalyst (34.0 mg,
2.5 mol %). The mixture was stirred at 100 °C for 24 h. Then the reaction
mixture was evaporated in vacuum, CH2Cl2 (3 Â 10 ml) was added to the
reaction mixture and the catalyst was filtered for the next cycle of the reaction.
The combined CH2Cl2 solution was removed by evaporation in vacuum and
was then subjected to silica gel column chromatograph; the one-pot three-
component aza-Friedel–Crafts product (5k) was obtained: 121.0 mg, isolated
yield 68%. N,N-Dimethyl-4-((1H-indol-3-yl)(4-methoxyphenyl)methyl)aniline
(5k). White solid, mp 160–162 °C (lit.20 162–164 °C). 1H NMR (500 MHz,
CDCl3) d 7.90 (s, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.25–7.23 (m, 1H), 7.14–7.13 (m,
3H), 7.08 (d, J = 9.0 Hz, 2H), 6.68 (d, J = 8.5 Hz, 2H), 6.98–6.95 (m, 1H), 6.81–
6.79 (m, 2H), 6.57–6.56 (m, 1H), 5.52 (s, 1H), 3.77 (s, 3H), 2.91 (s, 6H); 13C NMR
(125 MHz, CDCl3) d: 157.8, 149.0, 137.0, 136.8, 132.9, 129.8, 129.5, 127.2,
123.8, 121.9, 121.0, 120.1, 119.2, 113.6, 112.8, 110.9, 55.2, 47.0, 40.8;
Crystallographic data for 5k: C24H23N2O, white prism, formula weight 355.44,
Monoclinic, P 21/c, a = 16.4165(9) Å, b = 5.8444(3) Å, c = 21.0166(11) Å, V =
References and notes
1. (a) Sichaem, J.; Surapinit, S.; Siripong, P.; Khumkratok, S.; Jong-aramruang, J.;
Tip-pyang, S. Fitoterapia 2010, 81, 830; (b) Geng, C.-A.; Liu, X.-K. Fitoterapia
2013, 89, 42; (c) Porter, J. K.; Bacon, C. W.; Robbins, J. D.; Himmelsbach, D. S.;
Higman, H. C. J. Agric. Food Chem. 1977, 25, 88; (d) Chen, H.; Bai, J.; Fang, Z.-F.;
Yu, S.-S.; Ma, S.-G.; Xu, S.; Li, Y.; Qu, J.; Ren, J.-H.; Li, L.; Si, Y.-K.; Chen, X.-G. J.
Nat. Prod. 2011, 74, 2438; (e) Reina, M.; Ruiz-Mesia, W.; Lopez-Rodriguez, M.;
Ruiz-Mesia, L.; Gonzalez-Coloma, A.; Martinez-Diaz, R. J. Nat. Prod. 2012, 75,
928.
2. (a) Mukhopadhyay, S.; Handy, G. A.; Funayama, S.; Cordell, G. A. J. Nat. Prod.
1981, 44, 696; (b) Gangjiee, A.; Zaware, N.; Devambatla, R. K. V.; Raghavan, S.;
Westbrook, C. D.; Dybdal-Hargreaves, N. F.; Hamel, E.; Mooberry, S. L. Bioorg.
Med. Chem. 2013, 21, 891.
3. Wang, M.-L.; Shih, C.-K.; Chang, H.-P.; Chen, Y.-H. Food Chem. 2013, 134, 811.
4. Mbeunkui, F.; Grace, M. H.; Lategan, C.; Smith, P. J.; Raskin, I.; Lila, M. A. J.
Ethnopharmacol. 2012, 139, 471.
5. Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.;
Rambaldi, M.; Varoli, L.; Landi, L.; Prata, C.; Berridge, M. V.; Grasso, C.; Fiebig, H.
H.; Kelter, G.; Burger, A. M.; Kunkel, M. W. J. Med. Chem. 2008, 51, 4563.
1904.33(17) Å3, Z = 4, Dcalcd = 1.240 g cmÀ3, R(int) = 0.0183, R1 = 0.0691, wR2
0.1935, GOF = 1.092, CCDC no. 951170.
=
20. Liu, J.; Hu, T.; Wang, L. Tetrahedron 2011, 67, 3420.