Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

Article abstract of DOI:10.3762/bjoc.13.278

The reactivity of 2-bromo- and 2, 5-dibromoselenophenes in Pd-catalyzed direct heteroarylation was investigated. From 2-bromo-selenophene, only the most reactive heteroarenes could be employed to prepare 2-heteroarylated selenophenes; whereas, 2, 5-dibrom

Full text of DOI:10.3762/bjoc.13.278

Reactivity of bromoselenophenes in palladium-catalyzed
direct arylations
Aymen Skhiri1,2, Ridha Ben Salem*2, Jean-François Soulé*1 and Henri Doucet*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2017, 13, 2862–2868.
1Institut des Sciences Chimiques de Rennes, UMR 6226
CNRS-Université de Rennes 1, "Organométalliques: Matériaux et
Catalyse", Campus de Beaulieu, 35042 Rennes, France and
2Laboratoire de Laboratoire de Chimie Organique LR 17ES08,
Université de Sfax, Faculté des Sciences de Sfax, Route de la Soukra
km 4, 3038 Sfax, Tunisia
doi:10.3762/bjoc.13.278
Received: 24 August 2017
Accepted: 04 December 2017
Published: 22 December 2017
Associate Editor: M. Rueping
Email:
Ridha Ben Salem* - ridhabensalem@yahoo.fr; Jean-François Soulé* -
jean-francois.soule@univ-rennes1.fr; Henri Doucet* -
henri.doucet@univ-rennes1.fr
© 2017 Skhiri et al.; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
C–H bond activation; catalysis; heteroarenes; palladium; selenophene
Abstract
The reactivity of 2-bromo- and 2,5-dibromoselenophenes in Pd-catalyzed direct heteroarylation was investigated. From 2-bromo-
selenophene, only the most reactive heteroarenes could be employed to prepare 2-heteroarylated selenophenes; whereas, 2,5-
dibromoselenophene generally gave 2,5-di(heteroarylated) selenophenes in high yields using both thiazole and thiophene deriva-
tives. Moreover, sequential catalytic C2 heteroarylation, bromination, catalytic C5 arylation reactions allowed the synthesis of un-
symmetrical 2,5-di(hetero)arylated selenophene derivatives in three steps from selenophene.
Introduction
(Hetero)aryl-substituted selenophenes represent a class of mole- (MX) as waste. In recent years, the Pd-catalyzed arylation, via a
cules which exhibit useful physical properties, especially for the C–H bond activation, of a broad range of heteroaromatics using
preparation of artificial photosynthetic systems for solar energy aryl halides as reaction partners was demonstrated to be particu-
conversion or for thin film transistor applications [1-3]. In most larly effective for the preparation of bi(hetero)aryls [22-31].
cases, these (hetero)arylated selenophenes are currently pre- Among the reported results, a few examples of Pd-catalyzed
pared through the use of transition-metal-mediated reactions direct arylations via the C–H bond activation of selenophenes
such as Stille [3-9], Suzuki [10-19], or Kumada [20] couplings using aryl halides as coupling partners have been reported [32-
[21] (Scheme 1a and b). However, all these procedures require 35]. Conversely, C–H bond activation methodology was em-
the preparation of an organometallic or a boron derivative of ployed in only in one case for the preparation of a heteroary-
one of the coupling partners, and provide an organometallic salt lated selenophene from a haloselenophene. Wipf et al. reported
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Beilstein J. Org. Chem. 2017, 13, 2862–2868.
matics such as thiazole, pyrrole, furan or imidazole derivatives
with aryl bromides [36]. 2-Bromoselenophene, which was
easily prepared by reaction of selenophene with N-bromosuc-
cinimide [37], and 2-ethyl-4-methylthiazole were employed as
model substrates for our study. Reactions performed at 130 °C
or 110 °C gave the expected arylated selenophene 1 in 55%
and 64% yields, respectively, with complete conversions of
2-bromoselenophene; whereas 1 was obtained in a higher
yield of 80% when the reaction was conducted at 90 °C
(Table 1, entries 1–3). At elevated temperature (110–130 °C),
2-bromoselenophene seems to afford larger amounts of
selenophene oligomers as side-products. The use of PdCl2 or
PdCl(C3H5)(dppb) as catalysts instead of Pd(OAc)2 or other
bases such as K2CO3, Cs2CO3, CsOAc or NaOAc afforded 1 in
lower yields (Table 1, entries 4–9). The influence of two other
solvents in this cross-coupling reaction was also examined. We
observed that both DMF and xylene in the presence of 2 mol %
Pd(OAc)2 catalyst with KOAc gave 1 in moderate yields
(Table 1, entries 10 and 11).
Table 1: Influence of the reaction conditions for the coupling of 2-ethyl-
4-methylthiazole with 2-bromoselenophene.a
Entry Catalyst
Solvent
Base
Yield (%)
Scheme 1: Reported Pd-catalyzed heteroarylations of bromose-
lenophenes.
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
DMA
DMA
DMA
DMA
KOAc
KOAc
KOAc
KOAc
KOAc
K2CO3
Cs2CO3
CsOAc
NaOAc
KOAc
KOAc
55b
64c
80
45
48
41
9
2
3
in 2014 that using ethyl oxazole-4-carboxylate as reaction
partner, the corresponding 2,5-bis(oxazol-2-yl)selenophene de-
rivative was formed in 45% yield (Scheme 1c) [17]. Moreover,
to our knowledge the Pd-catalyzed direct heteroarylation of
2-bromoselenophene has not yet been described. Therefore, the
reactivity of 2-bromo- and 2,5-dibromoselenophenes in Pd-cata-
lyzed direct couplings with heteroarenes needed to be investi-
gated.
4
5
PdCl(C3H5)(dppb) DMA
6
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
DMA
DMA
DMA
DMA
DMF
xylene
7
8
52
17
53
48
9
10
11
aConditions: catalyst (0.02 equiv), 2-bromoselenophene (1 equiv),
2-ethyl-4-methylthiazole (1.5 equiv), base (2 equiv), 24 h, 90 °C, isolat-
ed yields of 1. b130 °C, c110 °C.
Herein, we wish to report on the reactivity of 2-bromoseleno-
phene, 2,5-dibromoselenophene and 2-aryl-5-bromose-
lenophenes in palladium-catalyzed direct heteroarylations with
a variety of heteroarenes using a phosphine-free palladium cata- Then, we investigated the scope of the coupling of 2-bromo-
lyst.
selenophene with a set of heteroarenes in the presence of
2 mol % Pd(OAc)2, KOAc as the base in DMA at 90 °C
(Scheme 2). The reaction of 2-isopropyl-4-methylthiazole gave
Results and Discussion
First, we examined the influence of the reaction temperature, the desired product 2 in 82% yield. Conversely, low yields in
using DMA as solvent, KOAc as base and 2 mol % Pd(OAc)2 the target products 3–5 were obtained for the reactions with
as catalyst (Table 1). We had previously observed that these thiophene-2-carbonitrile, 2-chlorothiophene and 2-pentylthio-
reaction conditions allowed the coupling of several heteroaro- phene, although complete conversions of 2-bromoselenophene
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Beilstein J. Org. Chem. 2017, 13, 2862–2868.
at C5-position of thiophene or pyrrole derivatives, for reaction
which proceed via concerted metallation–deprotonation [38-40],
are higher than that of thiazoles (see bottom of Scheme 2) [42].
We assume that, due to these higher energies of activation for
reactions with thiophene or pyrrole, larger amounts of
selenophene oligomers were formed in the presence of these
less reactive heteroarenes. Then, the reactivity of imidazo[1,2-
a]pyridine, which contains a very reactive C–H bond at C3-po-
sition was examined. The expected product 7 was obtained in a
high yield of 81%. Thus, for Pd-catalyzed direct heteroaryla-
tions of 2-bromoselenophene, only the heteroarenes containing
C–H bonds with low Gibbs free energies of activation [41]
should be employed.
By contrast, the direct arylation reactions with 2,5-dibromo-
selenophene were found to tolerate both thiazole and thiophene
derivatives (Scheme 3). The coupling of 3 equiv of thiazole de-
rivatives with 2,5-dibromoselenophene in the presence of
2 mol % Pd(OAc)2 and KOAc as base gave the corresponding
2,5-diheteroarylated selenophenes 8 and 9 in 78% and 80%
yields, respectively. The use of 2-pentyl- and 2-chlorothio-
phenes also gave the desired products 10 and 11 in high yields.
In general, the Pd-catalyzed direct arylation of 3-substituted
thiophenes with aryl halides afforded quite regioselectively the
C2-arylated thiophenes [30]. A similar regioselectivity was
oberved for the coupling of thiophene derivatives containing
methyl- or chloro-substituents at the C3-position with 2,5-
dibromoselenophene. In both cases, regioselective arylations at
Scheme 2: Palladium-catalyzed heteroarylations of 2-bromoseleno-
phene. *: 110 °C
were observed. A similar result was obtained for the reaction the C2-positions were observed, affording the 2,5-diarylated
with 1-phenylpyrrole. Reactions performed at a higher tempera- selenophenes 12 and 13 in 69% and 72% yields, respectively.
ture with thiophene-2-carbonitrile, 2-chlorothiophene afforded 3 From 2,5-dibromoselenophene and an excess of 1-methyl-
and 4 in slightly lower yields. Gorelsky calculated that the pyrrole, the expected 2,5-diarylated selenophene 14 was ob-
Gibbs free energies of activation for the cleavage of C–H bonds tained in 81% yield.
Scheme 3: Palladium-catalyzed 2,5-diheteroarylation of 2,5-dibromoselenophene.
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Beilstein J. Org. Chem. 2017, 13, 2862–2868.
Finally, we show a sequential transformation leading to 2-aryl- Conclusion
5-(heteroaryl)selenophenes in three steps from commercially In summary, the reactivity of 2-bromoselenophenes was investi-
available compounds (Scheme 4). Bromination at the C5-posi- gated and revealed that the C2-heteroarylation of 2-bromo-
tion of 2-arylselenophenes containing nitrile, acetyl or chloro selenophene in high yields is only possible with specific
substituents on the aryl moiety, which could be easily obtained heteroarenes such as thiazoles and imidazopyridines, whereas
in good yields from selenophene and aryl bromides via a thiophene or pyrroles gave the desired products in low yields.
Pd-catalyzed direct arylation using a reported procedure [33], Conversely, 2,5-dibromoselenophene was successfully coupled
afforded the 2-aryl-5-bromoselenophenes 15–17 in 84–90% with both thiazoles and thiophenes in the presence of phos-
yields. Then, a second Pd-catalyzed direct arylation using phine-free Pd(OAc)2 catalyst precursor and KOAc as inexpen-
heteroarenes and 15–17 as reaction partners, provided the target sive base, affording the desired 2,5-diheteroarylated seleno-
compounds 18–26 in high yields. Both thiazole and thiophene phenes in high yields. We also described that the sequential cat-
derivatives were successfully employed in this transformation. alytic C2-arylation, bromination, and catalytic C5-arylation of
The reaction tolerates useful functional groups on both cou- selenophene provides the controled double (hetero)arylation at
pling partners such as nitrile, acetyl or chloro. It should be the C2 and C5 positions of selenophene in good yields.
mentioned that again a regioselective arylation at the C2-posi-
tion of 3-chlorothiophene was observed affording 26 in 72%
Experimental
yield.
General procedure for palladium-catalyzed
direct mono-heteroarylations of 2-bromo-
Although the mechanism of these reactions was not elucidated,
the catalytic cycle shown on Scheme 5 can be proposed. The selenophene
first step is probably the oxidative addition of the 2-bromo- The reaction of the heteroarene (1.5 mmol), 2-bromoseleno-
selenophene to Pd(0) to afford the Pd(II) intermediate A. phene (0.210 g, 1 mmol) and KOAc (0.196 g, 2 mmol) at 90 °C
Then, after elimination of KBr with KOAc, a concerted metala- during 24 h in DMA (4 mL) in the presence of Pd(OAc)2
tion–deprotonation pathway involving an heteroarene gives B. (4.5 mg, 0.02 mmol), under argon affords the coupling
Reductive elimination affords the 2-heteroarylated selenophene products 1–7 after evaporation of the solvent and purification
with regeneration of the Pd(0) species.
on silica gel. Eluents: Pentane for compounds 3 and 4.
Scheme 4: Synthesis of 2-aryl-5-(heteroaryl)selenophenes.
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Beilstein J. Org. Chem. 2017, 13, 2862–2868.
Scheme 5: Proposed catalytic cycle.
General procedure for palladium-catalyzed
direct mono-heteroarylations of 2-bromo-5-
arylselenophenes
EtOAc/pentane 2:98 for compounds 1 and 6. EtOAc/pentane
10:90 for compound 2 and 5 and EtOAc/pentane 40:60 for com-
pound 7.
The reaction of the heteroarene (1.2 mmol), 2-bromo-5-arylse-
lenophene 15–17 (1 mmol) and KOAc (0.392 g, 4 mmol) at
150 °C during 16 h in DMA (4 mL) in the presence of
Pd(OAc)2 (4.5 mg, 0.02 mmol), under argon affords the cou-
pling products 18–26 after evaporation of the solvent and purifi-
cation on silica gel. Eluents: Pentane for compounds 21 and 22.
EtOAc/pentane 5:95 for compounds 18 and 19. EtOAc/pentane
10:90 for compounds 20, 23, 24 and 26. EtOAc/pentane 20:80
for compound 25.
General procedure for palladium-catalyzed
direct diheteroarylations
The reaction of the heteroarene (3 mmol), 2,5-dibromoseleno-
phene (0.289 g, 1 mmol) and KOAc (0.392 g, 4 mmol) at 90 °C
during 40 h in DMA (4 mL) in the presence of Pd(OAc)2
(4.5 mg, 0.02 mmol), under argon affords the coupling prod-
ucts 8–14 after evaporation of the solvent and purification on
silica gel. Eluents: Pentane for compounds 10–13. EtOAc/
pentane 5:95 for compounds 8, 9 and 14.
Supporting Information
General procedure for the synthesis of
5-bromo-2-arylselenophenes 15–17
Supporting Information File 1
To a mixture of the 2-arylselenophene [2] (2 mmol) in DMF
(5 mL) at 0 °C, N-bromosuccinimide (0.392 g, 2.2 mmol) was
slowly added. Then, the mixture was allowed to increase to
room temperature and stirred during 20 h. After addition of
water, the extraction was carried out with diethyl ether. Then,
the organic phase was dried over magnesium sulphate.
Finally, evaporation of the solvent and purification on silica gel
afforded the 5-bromo-2-arylselenophenes 15–17. Eluents:
Pentane for compounds 15 and 16. EtOAc:pentane 5:95 for
compound 17.
Additional experimental and analytical data and copies of
NMR spectra.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-13-278-S1.pdf]
Acknowledgements
We are grateful the CNRS, Rennes Metropole and Scientific
Ministry of Higher Education and Research of Tunisia for pro-
viding financial support.
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Beilstein J. Org. Chem. 2017, 13, 2862–2868.
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ORCID® iDs
Ridha Ben Salem - https://orcid.org/0000-0002-5179-351X
Jean-François Soulé - https://orcid.org/0000-0002-6593-1995
Henri Doucet - https://orcid.org/0000-0002-1410-3663
See for the synthesis of heteroarylated selenophenes via Kumada
coupling.
21.Skhiri, A.; Ben Salem, R.; Soulé, J.-F.; Doucet, H. ChemCatChem
2017, 9, 2895–2913. doi:10.1002/cctc.201700256
See for a review on the arylation of selenophenes via Pd-catalyzed
reactions.
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