Heterobimetallic Pd-Sn catalysis: A Suzuki, tandem ring-closing sequence toward indeno[2,1-b]thiophenes and indeno[2,1-b]indoles

Article abstract of DOI:10.1021/ol3021995

Indeno[2,1-b]thiophene and indeno[1,2-b]indole motifs have been obtained in moderate to good yields from easily available substituted boronic acids, 2-bromo aryl/vinyl aldehydes, and nucleophiles such as arenes/heteroarenes and others using a catalytic co

Full text of DOI:10.1021/ol3021995

ORGANIC
LETTERS
2012
Vol. 14, No. 18
4870–4873
Heterobimetallic PdÀSn Catalysis: A
Suzuki, Tandem Ring-Closing Sequence
toward Indeno[2,1‑b]thiophenes and
Indeno[2,1‑b]indoles
Debjit Das,† Sanjay Pratihar,† and Sujit Roy*,‡
Organometallics & Catalysis Laboratory, Department of Chemistry, Indian Institute of
Technology, Kharagpur 721302, India, and Organometallics & Catalysis Laboratory,
School of Basic Sciences, Indian Institute of Technology, Bhubaneswar 751013, India
sujitroy.chem@gmail.com, sroychem@iitbbs.ac.in
Received August 8, 2012
ABSTRACT
Indeno[2,1-b]thiophene and indeno[1,2-b]indole motifs have been obtained in moderate to good yields from easily available substituted boronic
acids, 2-bromo aryl/vinyl aldehydes, and nucleophiles such as arenes/heteroarenes and others using a catalytic combination of bimetallic
“PdÀSn” and AgPF6. This formal three-component coupling involves a Suzuki reaction followed by nucleophile assisted tandem ring closure. The
sequential synthesis of substituted heterocycle-fused indenes, benzofluorene, and fluorenes was also accomplished.
Heterocycle-fused indenes and indenofluorenes have
recently attracted attention in view of a number of promis-
ing factors. For example an indenofluorenyl core is an
important building block for blue fluorescent organic light
emitting diodes (OLEDs), organic field effect transistors,
organic solar cells, and green phosphorescent OLEDs
(PhOLEDs).1 On the other hand indenothiophenes and
indenoindoles constitute a very important class of hetero-
cyclic ligands used for the design of organometallic
catalysts.2,3 Metallocene catalysts derived from these li-
gands show very high activity in the polymerization of
olefins.2,3 Also, the oligothiophene skeleton bearing ter-
minal unsubstituted or substituted indeno[1,2-b]thiophene
represents a promising class of organic materials for p-type
organic semiconductors.4 Additionally, 5,10-dihydroindeno-
[l,2-b]indoles exhibit a wide range of biological activities and
† Indian Institute of Technology, Kharagpur.
‡ Indian Institute of Technology, Bhubaneswar.
(1) (a) Thirion, D.; Rault-Berthelot, J.; Vignau, L.; Poriel, C. Org.
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Lett. 2011, 13, 4418. (b) Poriel, C.; Barriere, F.; Thirion, D.; Rault-
Berthelot Chem.;Eur. J. 2009, 15, 13304. (c) Jacob, J.; Sax, S.; Piok, T.;
(2) Laishevtsev, I. P.; Kashulin, I. A; Taidakov, I. V.; Bagrov, V. V;
Nifant’ev, I. E. Chem. Heterocycl. Compd. 2003, 39, 553 and references
therein.
€
List, E. J. W.; Grimsdale, A. C.; Mullen, K. J. Am. Chem. Soc. 2004, 126,
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6987. (d) Thirion, D.; Poriel, C.; Metivier, R.; Rault-Berthelot, J.;
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Barriere, F.; Jeannin, O. Chem.;Eur. J. 2011, 17, 10272. (e) Kowada,
(3) Grandini, C.; Camurati, I.; Guidotti, S.; Mascellani, N.; Resconi,
L. Organometallics. 2004, 23, 344.
T.; Kuwabara, T.; Ohe, K. J. Org. Chem. 2010, 75, 906. (f) Cocherel, N.;
Poriel, C.; Rault-Berthelot, J.; Barriere, F.; Audebrand, N.; Slawin,
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A. M. Z.; Vignau, L. Chem.;Eur. J. 2008, 14, 11328. (g) Grimsdale,
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C-H. L.; Allain, M.; Blanchard, P.; Roncali, J. J. Org. Chem. 2009, 74,
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C.; Metivier, R.; Rault-Berthelot, J.; Barriere; Thirion, D.; F.; Jeannin,
O. Chem. Commun. 2011, 47, 11703 and references therein.
r
10.1021/ol3021995
Published on Web 08/31/2012
2012 American Chemical Society

are potential nontoxic antioxidant, membrane stabilizing
agents.5 Few synthetic routes are available for indenothio-
phenes and indenoindoles.2,4,6 To the best of our knowledge,
there are only a few reports of indeno[1,2-b]thiophenes and
indeno[1,2-b]indoles having varied substitution at the 8/10
positions.2,4a,6c This provides an opportunity to develop new
and efficient methods for selective design of heterocycle-fused
indenes. In this regard, a tandem catalysis approach appears
to be synthetically attractive.7
Keeping this in view we wished to construct the inde-
nothiophene/indenoindole core 4 from corresponding
aldehyde 3 and nucleophiles (such as arene, heteroarene,
1,3-diketo, alcohol, amine, and thiol) via a tandem ring-
closing route (Scheme 1). Precursor 3 could be synthesized
in a straightforward manner by Suzuki coupling8 between
1 and 2. The Lewis acidic activation of aldehyde 3 accom-
panied by tandem ring closing would furnish 4.
Scheme 2. Preparation of PdÀSn Heterobimetallics
(for details please see Supporting Information), PdCl-
(PPh3)2SnCl3 C2 was selected as the catalyst. The Suzuki
coupling between various aryl and heteroaryl substituted
boronic acids 2 with bromo derivatives 1 afforded the
desiredmotif3 inmoderate toexcellent yields (Figure1;for
details please see Supporting Information).
To test the tandem ring-closing reaction of 3 in the
presence of a nucleophile, the model reaction between
2-(thiophen-3-yl)benzaldehyde 3a and 2-methylthiophene
was studied, which gave rise to 8-(5-methylthiophen-2-yl)-
8H-indeno[2,1-b]thiophene 4a (Table 1).
Scheme 1. Retrosynthesis
Our continuing effort to develop bimetallic catalysis for
carbonÀcarbon and carbonÀheteroatom bond formation9
encouraged us to test the efficacy of a heterobimetallic
‘PdÀSn’ catalyst in mediating both the Suzuki and ring-
closing reactions. In view of the importance of ligands in
catalysis,10 we synthesized discrete heterobimetallic
‘PdÀSn’ complexes with diene and phosphine ligands via
the insertion reaction of SnCl2 across PdCl2(MeCN)2
(Scheme 2).11
Figure 1. Construction of motif 3 via Suzuki coupling.
Table 1. Screening of Catalysts for Cyclizationa
For the synthesis of arylaldehyde 3 via Suzuki coupling,
the model reaction between 4-bromobenzaldehyde and
phenylboronic acid was chosen. Based on TOF values
(5) (a) Graupner, P. R.; Mabon, M. F.; Ninan, A.; Sainsbury, M.;
€
Shertzer, H. G. Tetrahedron Lett. 1995, 36, 5827. (b) Talaz, O.; Gulc-in,
:
€
I.; Goksu, S.; Saracoglu, N. Bioorg. Med. Chem. 2009, 17, 6583.
(6) For few selected references: (a) Kashulin, I. A.; Nifant’ev, I. E.
J. Org. Chem. 2004, 69, 5476. (b) Chernyak, N.; Tilly, D.; Li, Z.;
Gevorgyan, V. Chem. Commun. 2010, 46, 150. (c) Fu, T. L.; Wang,
I. J. Dyes Pigm. 2008, 76, 590. (d) Barolo, S. M.; Lukach, A. E.; Rossi,
R. A. J. Org. Chem. 2003, 68, 2807. (e) Li, G.; Wang, E.; Chen, H.; Li, H.;
Liu, Y.; Wang, P. G. Tetrahedron 2008, 64, 9033. (f) Jewett, J. C.; Sletten,
E. M.; Bertozzi, C. R. J. Am. Chem. Soc. 2010, 132, 3688. (g) MacDowell,
D. W. H.; Patrick, T. B. J. Org. Chem. 1967, 32, 2441.
(7) (a) Wasilke, J. C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C. Chem.
Rev. 2005, 105, 1001. (b) Tietze, L. F. Chem. Rev. 1996, 96, 115.
(8) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (b)
Nicolaou, K. C.; Bulger, P. G; Sarlah., D. Angew. Chem., Int. Ed.
2005, 44, 4442.
(9) (a) Choudhury, J.; Podder, S.; Roy, S. J. Am. Chem. Soc. 2005,
127, 6162. (c) Chatterjee, P. N.; Roy, S. J. Org. Chem. 2010, 75, 4413. (d)
Podder, S.; Choudhury, J.; Roy, S. J. Org. Chem. 2007, 72, 3129. (e)
Podder, S.; Choudhury, J.; Roy, U. K.; Roy, S. J. Org. Chem. 2007, 72,
3100. (f) Maity, A. K.; Roy, S. J. Org. Chem. 2012, 77, 2935.
(10) (a) Weng, Z.; Teo, S.; Hor, T. S. A. Acc. Chem. Res. 2007, 40,
676. (b) Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47,
6338.
additive
(mol %)
time
(h)
yieldb
(%)
entry
catalyst (mol %)
1
2
3
4
5
6
7
PdCl(COD)SnCl3 (10)
PdCl(PPh3)2SnCl3 (05)
PdCl(COD)SnCl3 (05)
PdCl2(COD) (05)
PdCl2 (05)
À
16
10
6
7
0
AgPF6 (05)
AgPF6 (05)
AgPF6 (05)
AgPF6 (05)
AgPF6 (10)
AgPF6 (10)
70
0
12
12
12
16
0
SnCl2 (10)
0
À
0
a A mixture of aldehyde (0.25 mmol), 2-methylthiophene (0.75 mmol),
catalyst, and AgPF6 in 2 mL of dry ClCH2CH2Cl was stirred at 85 °C
for an appropriate time. b 1H NMR yield using triphenylmethane as an
external standard.
(11) (a) Das, D.; Pratihar, S.; Roy, U. K.; Mal, D.; Roy, S. Org.
ꢁ
Biomol. Chem. 2012, 10, 4537. (b) Noskowska, M.; Sliwinska, E.;
Duczmal, W. Transition Met. Chem. 2003, 28, 756.
Org. Lett., Vol. 14, No. 18, 2012
4871

to good yields (Figure 2). In our hands, only electron-
rich arenes (such as 2,4,6-trimethoxybenzene and 3,5-
dimethylphenol) were active, and the corresponding cy-
clized products 4e and 4f were obtained in 68% and 40%
yield, respectively. Arenes such as anisole, toluene, and
benzene were unreactive.13 In addition to arenes and hetero-
arenes, substituted 1,3-dicarbonyls and organometallic nu-
cleophiles such as allylsilane also promoted the desired ring-
closing reaction leading to cyclized products 4gÀ4i and 4j.
Using amine, thiol, and alcohol as nucleophiles, we could
construct CÀN, CÀS, and CÀO linkages at the 8-position
of the indenothiophene moiety (as in 4l, 4m, 4n, 4o, and 4k).
Interestingly, both aliphatic and aromatic thiols were active
as nucleophiles (products 4n and 4o). However, aliphatic
amines and aromatic alcohols were unreactive. In the case of
aromatic alcohols, C-alkylation was observed as in 4f. R,β-
Unsaturated aldehyde 3e was less reactive due to a decreased
electrophilicity at the carbonyl carbon, and tandem ring
closing was successful in the presence of indole, amine, and
thiol, albeit with a lower yield of the desired product
(4pÀ4r). In the case of the bifunctional nucleophile 2-mer-
captoethanol, only 4r (from the ÀSH attack) was obtained.
As in the case of indenothiophene, the indenoindole ring was
also successfully formed from tert-butyl 2-(2-formylphenyl)-
1H-indole-1 carboxylate 3j14,15 with carbon and heteroatom
nucleophiles in moderate to high yields (Figure 3), but
allylsilanes and alcohols were unreactive. We failed to pre-
pare the indeno[2,1-b]furan moiety from the corresponding
2-(furan-3-yl)benzaldehyde 3f and 2-methyl thiophene under
standard reaction conditions.
Figure 2. Substrate scope in nucleophile assisted tandem ring closing.
Using PdCl(COD)SnCl3 C1 alone, we observed negligi-
ble formation of 4a (entry 1, Table 1). Gratifingly, the
reactivity of C1 was dramatically enhanced in the pres-
ence of AgPF6 (entry 3).12 Individually AgPF6 as well as
PdCl2(COD)/AgPF6, SnCl2/AgPF6, PdCl2/AgPF6, and
[PdCl(PPh3)2SnCl3]/AgPF6 were ineffective toward the
cyclization of 3a.
With the above results in hand, we have successfully
tested the ring closing of 3aÀ3d with various nucleophiles
in the presence of the catalytic C1/AgPF6 combination
(Figure 2). In the case of heteroarenes (such as indole,
thiophene, and furan derivatives) as a nucleophile, the
desired cyclized products 4aÀ4d were obtained in moderate
Figure 3. Various 10-substituted indeno[1,2-b]indoles.
(13) Others and our group have recently addressed the issue of
nucleophilicity of arenes and heteroarenes in organic reactions. Please
see: (a) Galabov, B.; Ilieva, S.; Koleva, G.; Allen, W. D.; Schaefer, H. F.;
Schleyer, P. R. WIREs Comput. Mol. Sci. 2012, doi:10.1002/wcms.1112.
(b) Pratihar, S.; Roy, S. J. Org. Chem. 2010, 75, 4957.
(12) While mechanistic details are awaited, AgPF6 could be ascribed
as a halogen abstractor leading to a more reactive cationic bimetallic
‘PdÀSn’ species. For catalysis via a dual combination of a transition
ꢁ
metal precursor and AgPF6, please see: (a) Corma, A.; Garcιa, H.;
Leyva, A. J. Organomet. Chem. 2005, 690, 3529. (b) Fuente-Hernandez,
(14) With 1-(tert-butoxycarbonyl)-1H-inden-2-ylboronic acid and
2-bromobenzaldehyde, a deboronation product was obtained as the
major product instead of the desired tert-butyl 2-(2-formylphenyl)-1H-
indole-1-carboxylate 3j by using C2.
ꢁ
A.; Costes, P.; Kalck, P.; Ruiz-Garcıa, J. A.; Jauregui-Haza, U.; Urrutigoıty,
´
M.; Dechy-Cabaret, O. Catal. Commun. 2010, 12, 142. (c) Werner, H.;
€
Munch, G.; Laubender, M. Inorg. Chim. Acta 2005, 358, 1510.
4872
Org. Lett., Vol. 14, No. 18, 2012

Figure 5. Crystal structure of 4o and 6b, DIAMOND plot with
30% probability thermal ellipsoids.
In conclusion, we have presented a synthetically attrac-
tive approach employing a PdÀSn hetereobimetallic cata-
lyst for a direct Suzuki coupling and tandem ring-closing
sequence for the synthesis of indenothiophenes and inde-
noindoles having varied substitution at the 8/10 positions.
Other heterocycle-fused indenes, fluorenes, and benzo-
fluorene were also made via a stepwise route.
Figure 4. Stepwise route to heterocycle-fused indenes, fluorenes,
and benzofluorene.
As indicated earlier, during the course of our investiga-
tion, we observed that less reactive arenes (such as anisole,
toluene, benzene) were inactive toward cyclization of 3a
and 3j. Interestingly, heteroarene substituted biaryl alco-
hols 5aÀ5c efficiently cyclized into the corresponding
hetero indeno core 6aÀ6c in the presence of C1/AgPF6
(Figure 4). Similarly, biaryl alcohols 5dÀ5f were used to
prepare fluorene 6d and 6e and benzo[c]fluorene 6f.
The structures of 4o and 6b were established by X-ray
crystallographic analysis (Figure 5).
Acknowledgment. Financial support of this work by
DST-New Delhi (to S.R.) and CSIR (to D.D. and S.P.) is
gratefully acknowledged.
Supporting Information Available. Experimental pro-
cedures and characterization data for new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(15) Pd(PPh3)4 was used to prepare 3j following the method as noted
€
in reference: Lotter, A. N. C.; Pathak, R.; Sello, T. S.; Fernandes, M. A.;
Otterlo, W. A. L. V.; Koning, C. B. D. Tetrahedron 2007, 63, 2263.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 18, 2012
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