A new approach for the synthesis of bisindoles through agOTf as catalyst

Article abstract of DOI:10.3762/bjoc.10.228

A novel approach for the catalyzed formation of bisindolylmethane derivatives (BIMs) is described. This methodology is the unique example where AgOTf has been successfully used for the activation of aldehydes, giving easy access to a broad range of bisind

Full text of DOI:10.3762/bjoc.10.228

A new approach for the synthesis of bisindoles through
AgOTf as catalyst
Jorge Beltrá1, M. Concepción Gimeno*1 and Raquel P. Herrera*2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 2206–2214.
1Departamento de Química Inorgánica. Instituto de Síntesis Química
y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza.
E-50009 Zaragoza, Spain and 2Departamento de Química Orgánica.
Instituto de Síntesis Química y Catálisis Homogénea (ISQCH),
CSIC-Universidad de Zaragoza. E-50009 Zaragoza, Spain
doi:10.3762/bjoc.10.228
Received: 26 June 2014
Accepted: 27 August 2014
Published: 17 September 2014
Email:
Associate Editor: M. Rueping
M. Concepción Gimeno* - gimeno@unizar.es; Raquel P. Herrera* -
raquelph@unizar.es
© 2014 Beltrá et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
Ag(I); aldehydes; bisindole; catalysis; indole
Abstract
A novel approach for the catalyzed formation of bisindolylmethane derivatives (BIMs) is described. This methodology is the unique
example where AgOTf has been successfully used for the activation of aldehydes, giving easy access to a broad range of bisindolyl
derivatives with excellent results. Moreover, the simplicity and easy operational methodology using a small amount of commer-
cially available AgOTf (1–3 mol %), one of the lowest catalytic charge used in this process to date, makes this procedure an alter-
native approach for this interesting and appealing reaction.
Introduction
Indole is an interesting structural motif present in more than antimicrobial or anti-inflammatory, among others (Figure 1)
3000 isolated natural products and embedded in many bio- [17]. Interestingly, BIMs have also been found to be potent anti-
logical systems [1-3]. Although this field has attracted a consid- cancer derivatives, also having antimetastatic activity, and clin-
erable attention over the past decades, the development of new ical studies have demonstrated that they could be potentially
synthetic [4,5] and catalytic [6-11] methods leading to function- used as chemotherapeutic agents against numerous forms of
alized indole derivatives is still an active field because their cancer [18-20].
application in drug discovery [12-14]. Indole is the structural
core unit of bisindolylmethane derivatives (BIMs), many of The great importance of bisindolylmethanes, has led many
them isolated from marine natural sources [15,16] and are an efforts dedicated to the development of new strategies for their
important class of indole derivatives which exhibit an appealing synthesis after the pioneering work reported by Fischer in 1886
range of biological properties such as antibacterial, antifungal, [24,25], and more particularly when aldehydes are involved in
2206

Beilstein J. Org. Chem. 2014, 10, 2206–2214.
Figure 1: Bisindolyl based important targets: 1 [21], 2 [22] and 3 [23].
their synthesis [26]. Considering the broad scope of application the desired bisindolyl products [39,40]. Our approach could
of BIMs together with their interesting biological properties, the significantly broaden the scope of this reaction, providing a new
development of new efficient, general and eco-friendly proto- and convenient protocol and avoiding some reported draw-
cols using benign catalytic systems with structurally different backs, such as the use of toxic metal ions, expensive solvents,
aldehydes and easy accessible catalysts still remains a contin- long reaction times, high temperature, anhydrous conditions,
uous demand.
tedious work-up, low product yields, higher catalyst loading,
reaction limited to aromatic aldehydes and formation of large
Among the variety of Lewis acids employed in this reaction amounts of wastes or byproducts.
such as In(OTf)3 (5 mol %)/[omim][PF6−] [27], LiClO4
(10 equiv) [28], Cp2ZrCl2 (5 mol %) [29], Yb-amberlyst Results and Discussion
(16 mol %) [30], SmI2(THF)2 (10 mol %) [31], Sb2(SO4)3 In the context of our research program focused on the synthesis
(5 mol %) [32], Dy(OTf)3 (5–10 mol %) [33], Ln(OTf)3 of new indole derivatives, we centered our attention in the
(0.10 M) [34], FeCl3·6H2O (5 mol %)/[omim][PF6−] [35], preparation of bisindolylmethane derivatives following a very
V(HSO4)3 (10 mol %) [36], Bi(NO3)3 (2–5 mol %) [37], or easy and straightforward procedure, in order to contribute to the
CeCl3·7H2O (10 M) [38], Ag is a good alternative since it is development of this field. Accordingly, we decided to evaluate
one of the most abundant, cheaper, readily available metals and the possibility of preparing BIMs from aldehydes and simple
also displays low toxicity. We disclose here a pioneering Ag(I) species (Scheme 1).
strategy for the synthesis of bisindolylmethane derivatives via
Ag activation of aldehydes. To the best of our knowledge, this In order to test the viability of this idea, the investigation was
is the first example where catalytic amounts of AgOTf afford started by exploring the efficiency of four easily accessible
Scheme 1: Test reaction using diverse Ag(I) species.
2207

Beilstein J. Org. Chem. 2014, 10, 2206–2214.
Ag(I) species in two reaction models (Scheme 1), and following in decreasing the catalyst loading without reducing the yield of
the course of the process by TLC until no qualitative advance of the process, although longer reaction time was required. Inter-
the reaction was observed. To our delight, AgOTf allowed an estingly, it was possible to decrease the catalytic amount of the
almost full conversion in a very clean reaction after less than catalyst until 1 mol %, to the best of our knowledge one of the
12 hours, measuring the conversion of the process by 1H NMR. smallest catalyst loading used in this reaction to date (Table 1,
In contrast, AgNO3, Ag2CO3 and AgOAc showed a lack of re- entry 12), although longer reaction times were necessary
activity for both aldehydes 5a and 5b. This could be in agree- compared with the use of 3 mol % (Table 1, entry 8). In all
ment with the higher coordination capacity of the tested cases, very clean crude products were found at the end of the
counterions, while OTf is considered to be low-coordinating process. At this point, the amount of aldehyde was scaled up to
with some cations, thus favouring the Lewis acid character of 0.5 mmol in order to facilitate the weighing of the catalyst
Ag(I) [41,42]. Bearing this promising result in mind, the without decreasing the yield of the process (Table 1, entries
ensuing screening was performed using AgOTf as catalyst and 10–14). Surprisingly, variation in the dilution of the reaction
exploring different key parameters of the reaction in order to afforded similar yield for the same reaction time (compare
reach the best reaction conditions (Table 1).
Table 1, entries 10 and 11 and entries 12 and 13). On the other
hand, the addition of an excess of indole did not give rise much
In the first screening of solvent, encouraging results were better results (Table 1, entries 9 and 14). In order to prove the
achieved with CHCl3 for 5 mol % of catalyst (Table 1, entry 4) efficiency of this catalytic system the background of the process
in short reactions times (5 h), without heating the reaction. was tested, demonstrating a lack of reactivity in absence of the
Good results were also obtained for the rest of solvents tested, catalyst (Table 1, entry 15). With all these results in mind, the
with the exception of MeOH which exhibited almost no reactiv- scope of the reaction was continued with 1 or 3 mol % of cata-
ity (Table 1, entry 6). At this point, and because there is a big lyst in CHCl3 (0.25–0.50 mL) (Table 2) as the best reaction
concern about sustainable chemistry, the next step was centered conditions.
Table 1: Screening of the catalytic synthesis of BIM derivatives 6aa.a
Entry
Solvent (mL)
AgOTf (mol %)
Time (h)
Conv. (%)b
1
Toluene (0.5)
CH3CN (0.5)
THF (0.5)
5
5
5
5
5
5
3
3
3
3
3
1
1
1
–
3.5
3.5
3.5
3.5
3.5
3.5
5
84
84
89
93
78
<5
64
83
88
83
79
89
86
81
<5
2
3
4
CHCl3 (0.5)
EtOAc (0.5)
MeOH (0.5)
CHCl3 (0.5)
CHCl3 (0.5)
CHCl3 (0.5)
CHCl3 (0.5)
CHCl3 (0.25)
CHCl3 (0.5)
CHCl3 (0.25)
CHCl3 (0.5)
CHCl3 (0.5)
5
6
7
8
18
18
18
18
24
24
24
24
9c
10d
11d
12d
13d
14c,d
15
aExperimental conditions: AgOTf (1 or 3 mol %), indole (4a, 1 mmol) in 0.25 or 0.5 mL of CHCl3 and aldehyde 5a (0.5 mmol). bConversion calculated
by 1H NMR using dimethyl fumarate as internal standard. cReaction performed using 1.5 equiv of indole. dReaction performed for 0.5 mmol scale of
aldehyde.
2208

Beilstein J. Org. Chem. 2014, 10, 2206–2214.
The evaluation of the scope of this Ag(I)-catalyzed method- slowly maybe due to steric factors (3 mol % of catalyst affords
ology was performed testing diverse commercially available 34% yield after 24 h). However, in order to increase the reac-
aldehydes and indoles giving easy access to a great number of tion rate preventing the evaporation of 5d, the process was
different substituted bisindoles 6 with very good results carried out with 5 mol % of catalyst and a higher yield was
(Table 2).
achieved (Table 2, entry 4). It is remarkable that the resulting
product starting from aldehyde 5g afforded interesting trisin-
As shown above, high yields were achieved in reasonable reac- dole analogue 6ag (Table 2, entry 7). Trisindoles are a less
tion time using a representative spectrum of aliphatic and explored class of indole derivatives but with potential anti-
aromatic aldehydes (Table 2, entry 1–10). Aldehyde 5d reacted cancer properties [26], and their synthesis is also an appealing
Table 2: Scope of the catalytic synthesis of BIM derivatives 6.a
Entry
1c
Indole
Aldehyde
Solvent (mL) Cat. (mol %) Time (h)
Product
Yield (%)b
>95
5
1
1
1
5
18
18
15
48
6aa
5a
5b
5c
4a
4a
4a
4a
2
0.25
0.50
0.50
6ab
6ac
6ad
89
90
89
3d
4d
5d
5
0.25
0.50
3
1
18
16
6ae
6af
81
4a
4a
5e
5f
6d
>95
7d
0.50
3
24
6ag
41
4a
5g
2209

Beilstein J. Org. Chem. 2014, 10, 2206–2214.
Table 2: Scope of the catalytic synthesis of BIM derivatives 6.a (continued)
8d
0.50
1
3
18
18
6ah
6ai
90
95
4a
4a
5h
5i
9
0.50
0.50
10
3
24
6aj
90
4a
4a
5j
11
12
0.50
0.50
5
1
24
18
6ak
6ba
70
85
5k
5a
4b
4c
13
0.50
0.50
1
3
18
24
6ca
6da
95
75
5a
5a
14d
4d
15d
0.50
1
8
6ea
93
5a
4e
aOtherwise indicated: AgOTf (1 or 3 mol %), indole 4a–e (1 mmol), CHCl3 (0.25 mL) and aldehyde/ketone 5a–k (0.5 mmol). bIsolated yields by flash
chromatography (SiO2; hexane/EtOAc, 8:2). cReaction performed using 5 mmol of aldehyde 5a and 10 mmol of indole (4a), for 1.4 g scale. dFor
0.2 mmol of aldehyde.
challenge. Due to the high insolubility of aldehyde 5g in the exhibited with indole 4d (Table 2, entry 14). Given the possi-
reaction medium, the reaction was performed with 5 mol % of bility that product 6ca could decompose in the column and in
catalyst, however moderate results were obtained in this case. order to prevent this drawback and the decomposition of other
Different solvents were also tested in order to improve the yield additional products, the reaction crude was filtered through
of final 6ag but only a 35% yield was obtained in EtOAc and no neutral alumina with Et2O, and very clean crude product spec-
reaction in THF, after 2 days. The use of different substituted trum was obtained. It is also possible that in some cases the
indoles 4b–e allowed the desired products to be obtained with yield could depend on the stability of the starting aldehyde since
excellent results (Table 2, entries 12–15). There is a clear they are used without previous distillation. This methodology
dependence between the electronic environment of the indole was also tested with the less active and explored ketone 5k and
and the yield of the final product, since less reactivity was the reaction rendered a high yield, although 5 mol % of catalyst
2210

Beilstein J. Org. Chem. 2014, 10, 2206–2214.
was required in order to decrease the reaction rate (Table 2,
entry 11). Additionally, the possibility of scaling up this process
was explored to obtain 1.4 g of product 6ab (Table 2, entry 2),
and successfully completed conversion was achieved after 18 h
of reaction with a very clean spectrum (see Supporting Informa-
tion File 1).
In order to prove the applicability of this methodology, the
scope of the reaction was extended to the synthesis of the
interesting compound vibrindole A (Scheme 2), an isolated
metabolite of the marine bacteria Vibrio parahaemolyticus,
which is active against Bacillus subtilis, Staphylococcus aureus
and Staphylococcus albus as has been previously demonstrated
[43].
In order to prevent the loss of acetaldehyde by evaporation (bp
20 °C) and the consequent poorer yield of the final product,
instead of 1 equivalent of aldehyde (0.5 mmol) 2 equivalents
(1 mmol) were used. The result was 90% of yield compared
with 67% for 1 equivalent of acetaldehyde, confirming our
concern. It is worth mentioning that this procedure allowed
excellent results using 1 mol % of catalyst, one of the lowest
catalytic charges used to date. This synthesis represents an
easier approach in comparison with previously reported
methods for the synthesis of vibrindole A [44-49]. After evapor-
ation of the solvent, a very clean crude product was obtained
since acetaldehyde is also evaporated, and the final product was
purified by a simple column chromatography. Moreover, we
were able to obtain single crystals for compounds 6ad and 6al
for the first time in the literature (Figure 2) [50].
Figure 2: Crystal structures for compounds 6ad and 6al.
Since HOTf is released in the second step of the reaction, it is
not possible to discard the participation of HOTf in the acti-
vation process, since the catalytic ability of these species has
been previously invoked by other authors, when metal triflates
are used as catalysts in other reactions [54]. Moreover, Brønsted
acids have also been employed as promoters of this process
[26]. We have performed a comparative study of the reaction
between indole (4a) and aldehyde 5a, one with HOTf (1 mol %)
and the other with AgOTf (1 mol %), showing that the reaction
rate of the process catalyzed by triflic acid is higher (after 6 h
the reaction is finished). This is also in agreement with the
results observed by Hartwig and co-workers [54]. These find-
ings indicate that AgOTf is the mean catalyst of the process,
because although triflic acid could participate in the activation
process, it would be consumed in the reaction with the produced
AgOH to regenerate AgOTf.
Although the mechanism is not clear at this stage, we can
assume the same mechanism as that previously proposed for
other Lewis acid (Scheme 3). In the course of the reaction after
the first addition of one molecule of indole to the aldehyde,
unstable intermediate 7 would promote the elimination of Ag(I),
in the form of AgOH, to give azafulvene 8 [51,52]. Finally, the
iminium 8 would undergo a further addition of a second mole-
cule of indole to produce the final observed products 6 [53].
Scheme 2: Synthesis of biologically active vibrindole A.
2211

Beilstein J. Org. Chem. 2014, 10, 2206–2214.
Representative procedure for the synthesis of bisindoles 6:
To a mixture of catalyst AgOTf (1 or 3 mol %) and indole 4a–e
(1 mmol) in CHCl3 (0.25–0.5 mL), aldehyde 5a–k (0.5 mmol)
was further added in a test tube at room temperature. After the
reaction time (see Table 2), the crude mixture was filtered
through neutral alumina with Et2O and the solvent was removed
under vacuum. Then, adducts 6 were finally isolated by flash
chromatography (SiO2; hexane/EtOAc, 8:2). Yield for each
final product is reported in Table 2. Final products should be
stored under nitrogen atmosphere and in the fridge.
3,3'-(3-phenylpropane-1,1-diyl)bis(1H-indole) (6ac)
Scheme 3: Mechanism of the synthesis of bisindoles through AgOTf
catalyst.
Following the general procedure, compound 6ac was obtained
after 15 h of reaction at room temperature in 90% yield. The
1H NMR spectrum is consistent with the values previously
reported in [57]. 13C APT-NMR (100 MHz, CDCl3) δ 142.6
Conclusion
In summary, we have reported for the first time an unprece- (1C), 136.6 (2C), 128.5 (2C), 128.2 (2C), 127.0 (2C), 125.6
dented approach of AgOTf-catalyzed addition of indoles to (1C), 121.8 (2C), 121.5 (2C), 120.0 (2C), 119.6 (2C), 119.0
aldehydes, providing easy access to interesting BIMs with very (2C), 111.1 (2C), 37.4 (1C), 34.4 (1C), 33.5 (1C).
good yields. This catalytic system has been proven active under
mild reaction conditions and effective for a broad application in 3,3'-(2,2-dimethylpropane-1,1-diyl)bis(1H-indole) (6ad)
the synthesis of aliphatic and aromatic substituted bisiindolyl-
methane derivatives. The small amount of catalyst (1–3 mol %)
used in our developed procedure is another advantage being one
of the lowest catalytic charge used to date for this process.
Furthermore, the simplicity and easy operational methodology
makes this procedure an excellent alternative approach for these
interesting and appealing reaction products, for which there is
still a continuous demand.
Following the general procedure, compound 6ad was obtained
after 48 h of reaction at room temperature in 89% yield. The
1H NMR spectrum is consistent with the values previously
Experimental
Purification of reaction products was carried out by flash chro- reported in [59]. 13C APT-NMR (100 MHz, CDCl3) δ 135.3
matography using silica gel (0.063–0.200 mm). Analytical thin- (2C), 128.7 (2C), 121.9 (2C), 121.6 (2C), 119.4 (2C), 119.2
layer chromatography was performed on 0.25 mm silical gel (2C), 119.1 (2C), 110.7 (2C), 43.1 (1C), 35.8 (1C), 29.0 (3C).
60-F plates. 1H NMR spectra were recorded at 400 MHz;
13C APT-NMR spectra were recorded at 100 MHz; CDCl3 as
Supporting Information
the solvent. Chemical shifts were reported in the δ scale rela-
tive to the central line of CDCl3 (77 ppm) for 13C APT-NMR.
Supporting Information File 1
All commercially available solvents and reagents were used as
received. The 1H and 13C NMR spectra for compounds 6aa
[55], 6ab [56], 6ac [57], 6ad [58], 6ae [35], 6af [59], 6ag [23],
6ah [60], 6ai [61], 6aj [58], 6ak [57], 6ba [62], 6ca [63], 6da
[64], 6ea [64], are consistent with values previously reported in
the literature.
1H NMR for all synthesized compounds, 13C APT-NMR
spectra for compounds 6ac and 6ad and crystallographic
data for compounds 6ad and 6al.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-10-228-S1.pdf]
2212

Beilstein J. Org. Chem. 2014, 10, 2206–2214.
23.Veluri, R.; Oka, I.; Wagner-Döbler, I.; Laatsch, H. J. Nat. Prod. 2003,
66, 1520–1523. doi:10.1021/np030288g
Acknowledgements
Authors thank the Ministerio de Economía y Competitividad
(MINECO/FEDER CTQ2010-19606 and CTQ2013-48635-C2-
1-P) and DGA-FSE (Research Group E-77) for financial
support.
24.Fischer, E. Chem. Ber. 1886, 19, 2988–2991.
doi:10.1002/cber.188601902296
25.Fischer, E. Justus Liebigs Ann. Chem. 1887, 242, 372–383.
doi:10.1002/jlac.18872420311
26.Shiri, M.; Zolfigol, M. A.; Kruger, H. G.; Tanbakouchian, Z. Chem. Rev.
2010, 110, 2250–2293. doi:10.1021/cr900195a
References
27.Ji, S.-J.; Zhou, M.-F.; Gu, D.-G.; Wang, S.-Y.; Loh, T.-P. Synlett 2003,
2077–2079. doi:10.1055/s-2003-41464
1. Ruiz-Sanchis, P.; Savina, S. A.; Albericio, F.; Álvarez, M.
Chem. – Eur. J. 2011, 17, 1388–1408. doi:10.1002/chem.201001451
2. Gribble, G. W. Top. Heterocycl. Chem. 2010, 26, 1–480.
doi:10.1007/978-3-642-15733-2
28.Yadav, J. S.; Reddy, B. V. S.; Murthy, C. V. S. R.; Kumar, G. M.;
Madan, C. Synthesis 2001, 783–787. doi:10.1055/s-2001-12777
29.Kantam, M. L.; Aziz, K.; Likhar, P. R. Catal. Lett. 2004, 98, 117–121.
doi:10.1007/s10562-004-7925-5
3. Vicente, R. Org. Biomol. Chem. 2011, 9, 6469–6480.
doi:10.1039/C1OB05750B
30.Yu, L.; Chen, D.; Li, J.; Wang, P. G. J. Org. Chem. 1997, 62,
3575–3581. doi:10.1021/jo961933+
And references therein cited.
4. Joule, J. A. Indole and its Derivatives. In Science of Synthesis;
Thomas, E. J., Ed.; Houben-Weyl Methods of Molecular
Transformations, Vol. 10; Thieme: Stuttgart, 2000; chapter 10.13.
5. Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875–2911.
doi:10.1021/cr0505270
31.Soueidan, M.; Collin, J.; Gil, R. Tetrahedron Lett. 2006, 47, 5467–5470.
doi:10.1016/j.tetlet.2006.05.169
32.Srinivasa, A.; Varma, P. P.; Hulikal, V.; Mahadevan, K. M.
Monatsh. Chem. 2008, 139, 111–115. doi:10.1007/s00706-007-0697-z
33.Mi, X.; Luo, S.; He, J.; Cheng, J.-P. Tetrahedron Lett. 2004, 45,
4567–4570. doi:10.1016/j.tetlet.2004.04.039
6. Bandini, M.; Melloni, A.; Tommasi, S.; Umani-Ronchi, A. Synlett 2005,
1199–1222. doi:10.1055/s-2005-865210
34.Chen, D.; Yu, L.; Wang, P. G. Tetrahedron Lett. 1996, 37, 4467–4470.
doi:10.1016/0040-4039(96)00958-6
7. Marqués-López, E.; Diez-Martinez, A.; Merino, P.; Herrera, R. P.
Curr. Org. Chem. 2009, 13, 1585–1609.
35.Ji, S.-J.; Zhou, M.-F.; Gu, D.-G.; Jiang, Z.-Q.; Loh, T.-P.
Eur. J. Org. Chem. 2004, 1584–1587. doi:10.1002/ejoc.200300719
36.Shirini, F.; Yahyazadeh, A.; Abedini, M.; Langroodi, D. I.
Bull. Korean Chem. Soc. 2010, 31, 1715–1718.
doi:10.2174/138527209789578126
8. Bandini, M.; Eichholzer, A. Angew. Chem., Int. Ed. 2009, 48,
9608–9644. doi:10.1002/anie.200901843
9. Terrasson, V.; de Figueiredo, R. M.; Campagne, J. M.
Eur. J. Org. Chem. 2010, 2635–2655. doi:10.1002/ejoc.200901492
10.Zeng, M.; You, S.-L. Synlett 2010, 1289–1301.
doi:10.1055/s-0029-1219929
doi:10.5012/bkcs.2010.31.6.1715
37.Khodaeia, M. M.; Ghanbary, P.; Mohammadpoor-Baltork, I.;
Memarian, H. R.; Khosropour, A. R.; Nikoofar, K. J. Heterocycl. Chem.
2008, 45, 377–381. doi:10.1002/jhet.5570450213
11.Chauhan, P.; Chimni, S. S. RSC Adv. 2012, 2, 6117–6134.
doi:10.1039/c2ra20544k
38.Silveira, C. C.; Mendes, S. R.; Líbero, F. M.; Lenardão, E. J.; Perin, G.
Tetrahedron Lett. 2009, 50, 6060–6063.
12.Lounasmaa, M.; Tolvanen, A. Nat. Prod. Rep. 2000, 17, 175–191.
doi:10.1039/a809402k
doi:10.1016/j.tetlet.2009.08.062
39.Buscemi, G.; Biffis, A.; Tubaro, C.; Basato, M.; Graiff, C.; Tiripicchio, A.
Appl. Organomet. Chem. 2010, 24, 285–290. doi:10.1002/aoc.1595
40.Shaikh, A. C.; Chen, C. J. Chin. Chem. Soc. 2011, 58, 899–905.
doi:10.1002/jccs.201190142
13.Hibino, S.; Choshi, T. Nat. Prod. Rep. 2001, 18, 66–87.
doi:10.1039/b004055j
14.Wu, Y.-J. Top. Heterocycl. Chem. 2010, 26, 1–29.
doi:10.1007/7081_2010_37
41.Hashmi, A. S. K. In Silver in Organic Chemistry; Harmata, M., Ed.;
Wiley: Hoboken, 2010; pp 357–379. doi:10.1002/9780470597521.ch12
42.Weibel, J.-M.; Blanc, A.; Pale, P. Chem. Rev. 2008, 108, 3149–3173.
doi:10.1021/cr078365q
15.Pindur, U.; Lemster, T. Curr. Med. Chem. 2001, 8, 1681–1698.
doi:10.2174/0929867013371941
16.Kochanowska-Karamyan, A. J.; Hamann, M. T. Chem. Rev. 2010, 110,
4489–4497. doi:10.1021/cr900211p
43.Bell, R.; Carmeli, S.; Sar, N. J. Nat. Prod. 1994, 57, 1587–1590.
doi:10.1021/np50113a022
17.Safe, S.; Papineni, S.; Chintharlapalli, S. Cancer Lett. 2008, 269,
326–338. doi:10.1016/j.canlet.2008.04.021
44.Gibbs, T. J. K.; Tomkinson, N. C. O. Org. Biomol. Chem. 2005, 3,
4043–4045. doi:10.1039/b513394g
18.Bell, M. C.; Crowley-Nowick, P.; Bradlow, H. L.; Sepkovic, D. W.;
Schmidt-Grimminger, D.; Howell, P.; Mayeaux, E. J.; Tucker, A.;
Turbat-Herrera, E. A.; Mathis, J. M. Gynecol. Oncol. 2000, 78,
123–129. doi:10.1006/gyno.2000.5847
45.Guo, X.; Pan, S.; Liu, J.; Li, Z. J. Org. Chem. 2009, 74, 8848–8851.
doi:10.1021/jo902093p
46.Niu, T.; Huang, L.; Wu, T.; Zhang, Y. Org. Biomol. Chem. 2011, 9,
273–277. doi:10.1039/c0ob00709a
19.Hong, C.; Firestone, G. L.; Bjeldanes, L. F. Biochem. Pharmacol. 2002,
63, 1085–1097. doi:10.1016/S0006-2952(02)00856-0
20.Le, H. T.; Schaldach, C. M.; Firestone, G. L.; Bjeldanes, L. F.
J. Biol. Chem. 2003, 278, 21136–21145. doi:10.1074/jbc.M300588200
21.Maciejewska, D.; Niemyjska, M.; Wolska, I.; Włostowski, M.;
Rasztawicka, M. Z. Naturforsch. 2004, 59b, 1137–1142.
22.Lee, C.-H.; Yao, C.-F.; Huang, S.-M.; Ko, S.; Tan, Y.-H.;
Lee-Chen, G.-J.; Wang, Y.-C. Cancer 2008, 113, 815–825.
doi:10.1002/cncr.23619
47.Tayebee, R.; Nehzat, F.; Rezaei-Seresht, E.; Mohammadi, F. Z.;
Rafiee, E. J. Mol. Catal. A: Chem. 2011, 351, 154–164.
doi:10.1016/j.molcata.2011.09.029
48.Abe, T.; Nakamura, S.; Yanada, R.; Choshi, T.; Hibino, S.; Ishikura, M.
Org. Lett. 2013, 15, 3622–3625. doi:10.1021/ol401486s
49.Huo, C.; Kang, L.; Xu, X.; Jia, X.; Wang, X.; Xie, H.; Yuan, Y.
Tetrahedron Lett. 2014, 55, 954–958. doi:10.1016/j.tetlet.2013.12.055
2213

Beilstein J. Org. Chem. 2014, 10, 2206–2214.
50.CCDC-1007024 (6ad) and CCDC-1007025 (6al) contain the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from the Cambridge Crystallographic Data
Centre via http://www.ccdc.cam.ac.uk/data_request/cif.
51.Cook, A. H.; Majer, J. R. J. Chem. Soc. 1944, 486–487.
doi:10.1039/JR9440000486
52.Cook, A. H.; Majer, J. R. J. Chem. Soc. 1944, 488–489.
doi:10.1039/JR9440000488
53.Burr, G. O.; Gortner, R. A. J. Am. Chem. Soc. 1924, 46, 1224–1246.
doi:10.1021/ja01670a015
54.Rosenfeld, D. C.; Shekhar, S.; Takemiya, A.; Utsunomiya, M.;
Hartwig, J. F. Org. Lett. 2006, 8, 4179–4182. doi:10.1021/ol061174+
55.Peng, Y.-Y.; Zhang, Q.-L.; Yuan, J.-J.; Cheng, J.-P. Chin. J. Chem.
2008, 26, 2228–2232. doi:10.1002/cjoc.200890396
56.Xu, H.-Y.; Zi, Y.; Xu, X.-P.; Wang, S.-Y.; Ji, S.-J. Tetrahedron 2013, 69,
1600–1605. doi:10.1016/j.tet.2012.11.098
57.Ramesh, C.; Banerjee, J.; Pal, R.; Das, B. Adv. Synth. Catal. 2003,
345, 557–559. doi:10.1002/adsc.200303022
58.An, L.-T.; Ding, F.-Q.; Zhou, J.-P.; Lu, X.-H.; Zhang, L.-L.
Chin. J. Chem. 2007, 25, 822–827. doi:10.1002/cjoc.200790151
59.Khalafi-Nezhad, A.; Parhami, A.; Zare, A.; Moosavi Zare, A. R.;
Hasaninejad, A.; Panahi, F. Synthesis 2008, 617–621.
doi:10.1055/s-2008-1032159
60.Magesh, C. J.; Nagarajan, R.; Karthik, M.; Perumal, P. T.
Appl. Catal., A: Gen. 2004, 266, 1–10.
doi:10.1016/j.apcata.2004.01.024
61.Thirupathi, P.; Kim, S. S. J. Org. Chem. 2010, 75, 5240–5249.
doi:10.1021/jo1010137
62.Dhiman, S.; Ramasastry, S. S. V. Org. Biomol. Chem. 2013, 11,
8030–8035. doi:10.1039/c3ob41945b
63.Pal, R.; Khannobis, S.; Sarkar, T. Chem. J. 2013, 3, 7–12.
64.Ramachandiran, K.; Muralidharan, D.; Perumal, P. T. Tetrahedron Lett.
2011, 52, 3579–3583. doi:10.1016/j.tetlet.2011.04.110
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.10.228
2214