A direct synthesis of selenophenes by Cu-catalyzed one-pot addition of a selenium moiety to (E,E)-1,3-dienyl bromides and subsequent nucleophilic cyclization

Article abstract of DOI:10.1021/ol501820e

An efficient protocol for the synthesis of selenophenes and selanyl selenophenes has been achieved by a simple one-pot reaction of 1,3-dienyl bromides and 1,3-dienyl-gem-dibromides respectively with KSeCN catalyzed by CuO nanoparticles. Several aryl, alke

Full text of DOI:10.1021/ol501820e

Letter
pubs.acs.org/OrgLett
A Direct Synthesis of Selenophenes by Cu-Catalyzed One-Pot
Addition of a Selenium Moiety to (E,E)‑1,3-Dienyl Bromides and
Subsequent Nucleophilic Cyclization
Pintu Maity, Debasish Kundu, Rajdip Roy, and Brindaban C. Ranu*
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India
S
* Supporting Information
ABSTRACT: An efficient protocol for the synthesis of selenophenes and selanyl selenophenes has been achieved by a simple
one-pot reaction of 1,3-dienyl bromides and 1,3-dienyl-gem-dibromides respectively with KSeCN catalyzed by CuO
nanoparticles. Several aryl, alkenyl, heteroaryl, and alkyl substituted selenophenes were obtained with a broad array of
functional group tolerance. This is found to be a general methodology for chalcogenophenes being effective for the synthesis of
thiophenes too.
halcogenophene derivatives are of considerable interest in
organic synthesis because of their useful applications as
to the formation of selenophenes where addition of a selenium
moiety to the dienyl system and subsequent nucleophilic
cyclization take place in one pot catalyzed by CuO nano-
particles (Scheme 1).
C
pharmaceuticals and materials.1 In this family, selenophenes
have received tremendous attention recently, as they have
shown promising photobiological2 and diverse biological
activities including antioxidant,3 antitumoral,4 anti-inflamma-
tory,5 antihypertensive,6 and anticonvulsant.7 In addition, these
compounds are versatile building blocks being used in the
synthesis of many biologically active compounds and natural
products.8 Thus, synthesis of selenophenes is of much
importance. Surprisingly the methods for their synthesis are
very limited. The classical methods for the synthesis of
selenophenes involved heating of hexane-2,5-dione and
phosphorus pentaselenide in a sealed tube9 or acetylene and
selenium powder.10 Obviously they required harsh conditions
and a high temperature, and thus their large scale application in
industry is limited.11 Recently, electrophilic cyclization of
homopropargyl selenides by I2 or ICl or CuX2 (4 equiv) and
subsequent oxidation by DDQ to produce halosubstituted
selenophenes has been reported.12 Another similar approach
involves one-pot electrophilic cyclization of selenoenynes
catalyzed by CuI/PhSeSePh.13 However, both of these
procedures are multistep as they require preparation of
homopropargyl selenide/selenoenynes in the initial step. A
recent report for the synthesis of benzothiophenes and
benzoselenophenes involves reaction of arylzinc reagents,
alkynes, and elemental chalcogens.14 However, it is limited to
benzochalcogenophenes only and did not address any
selenophenes and thiophenes as a unit. Thus, development of
an efficient and convenient method for the preparation of
selenophenes still remains a challenging task.
Scheme 1. Copper Catalyzed Coupling of 1,3-Dienyl
Bromides with KSeCN
To standardize the reaction conditions a series of experi-
ments for a representative reaction of (E,E)-4-phenyl-1,3-dienyl
bromide and KSeCN with variation of reaction parameters such
as solvent, catalyst loading, Cu-source, temperature, and
reaction time were performed. 20 mol % CuO was found to
We report here a conceptually different and novel protocol
involving coupling of 1,3-dienyl bromides with KSeCN leading
Received: June 24, 2014
Published: July 25, 2014
© 2014 American Chemical Society
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Letter
be most effective in catalyzing the reaction in DMF at 110 °C
(Table 1, entry 1). DMSO and NMP were also found to be
Scheme 2. Synthesis of Substituted Selenophenes by Copper
Catalyzed Coupling of KSeCN and 1,3-Di-enyl Bromides
a
Table 1. Standardization of Reaction Conditions
a
entry
catalyst
CuO
catalyst (mol %)
solvent
DMF
yield (%)
1
2
3
4
5
6
7
8
9
20
20
20
20
20
20
20
20
20
20
15
20
−
90
CuO
DMSO
NMP
84
CuO
86
CuO
toluene
CH3CN
1,4-dioxane
H2O
−
−
−
−
trace
trace
−
CuO
CuO
CuO
Cu(OAc)2
Cu(acac)2
CuO
DMF
DMF
b
10
DMF
a
11
CuO
DMF
48
Reaction conditions: 1,3-dienyl bromide (1 mmol), KSeCN (1.2
c
12
CuO
DMF
trace
trace
30
mmol), CuO (20 mol %), DMF (2 mL), 110 °C, 12 h.
13
−
CuO
DMF
d
14
20
DMF
selanyl selenophenes were obtained (Scheme 3). Several
diverse aryl substituted 1,3-dienyl-gem-dibromides underwent
a
Reaction conditions: (E,E)-4-phenyl-1,3-dienyl bromide (0.5 mmol),
KSeCN (0.6 mmol), CuO NP (20 mol %), DMF, 110 °C, 12 h.
b
c
Reaction was carried out at 90 °C. Se powder was used in place of
Scheme 3. Synthesis of Selanyl Selenophenes by Coupling of
d
a
KSeCN. CuO powder (non NP) was used.
1,3-Di-enyl-gem-dibromides and KSeCN
effective (Table 1, entries 2−3). Toluene, CH3CN, and dioxane
failed to initiate the reaction (Table 1, entries 4−6). The
reaction did not proceed at all in H2O (Table 1, entry 7). Only
marginal formation of the product was observed when 20 mol
% of Cu(OAc)2 and Cu(acac)2 were used as the catalyst (Table
1, entries 8 and 9). The reaction did not progress at lower
temperature (90 °C) (Table 1, entry 10). Use of 15 mol % of
the catalyst lowered the yield of the reaction (Table 1, entry
11). Use of Se(0) powder in place of KSeCN did not produce
any encouraging result (Table 1, entry 12). Virtually no product
was formed in the absence of any catalyst (Table 1, entry 13).
The reaction using ordinary CuO powder (non NP) provided
only a 30% yield of product (Table 1, entry 14).
Thus, in a typical procedure, a mixture of 1,3-dienyl bromide
and KSeCN was heated in DMF at 110 °C in the presence of
20 mol % of CuO nanoparticles for a certain period of time
(TLC). The results are summarized in Scheme 2. A variety of
aryl or alkyl substituted 1,3-dienyl bromides underwent
selenylation followed by cyclization to produce the correspond-
ing selenophenes. Both electron-donating and -withdrawing
group substituted dienyl bromides are compatible in this
reaction (Me, 2b, OMe, 2f, Cl, 2d, NO2, 2g). Reactions with
aryl-1,3-dienyl bromides having alkyl substituents (-Me, -pentyl,
and Cl) on the vinyl carbon were successful, producing 2-
phenyl-3-alkyl selenophenes (2b, 2h, 2c). Long alkyl chain
substituted 1,3-dienyl bromides also produced the correspond-
ing selenophenes (2i) although 4-Me- and unsubstituted
counterparts did not produce any product. Interestingly 1,3,5-
trienyl bromide furnished 2-vinyl selenophene only (2j) and
formation of no selenepine was observed. This procedure is
also effective for the synthesis of tetrahydro benzo[b]
selenophenes from the corresponding 1,3- dienyl bromides
(2k, 2l).
a
Reaction conditions: 1,3-dienyl-gem-dibromide (1 mmol), KSeCN
b
(3.0 mmol), CuO (20 mol %), DMF (2 mL), 110 °C, 8 h. 10 h.
reactions using this procedure to produce the corresponding
products. The heteroaryl furan substituted 1,3-dienyl-gem-
dibromide also participated in this reaction successfully to
provide 4h. The identity of 4h was established by spectroscopic
and crystallographic data15 (Figure 1).
The 1,3,5-trienyl-gem-dibromide furnished selanyl vinyl
substituted selenophenes (4i) without any difficulty. Signifi-
cantly, formation of no diselenepinyl selenide was observed.
Interestingly, the reactions of alkyl substituted 1,3-dienyl-
gem-dibromides under similar conditions using 3 equiv of
KSeCN produced a mixture of selanyl selenophenes and
diselanyl selenophenes in varying ratios (NMR) (Scheme 4).
When 1,3-dienyl-gem-dibromides were subjected to reaction
under these conditions in the presence of 3 equiv of KSeCN,
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Letter
chromatography. A wide variety of sensitive functionalities are
compatible with the reaction conditions. Many of these
selenophenes are reported for the first time, and these
molecules, particularly the diheteroaryl selenophene 4h, may
be of interest for biological screening. The compound 2i was
found as a precursor of CIOS-Dye which is a high molar
extinction coefficient sensitizer in dye-sensitized solar cells.16
To extend the scope of this strategy for the synthesis of
thiophenes when the reaction was performed with KSCN
under identical reaction conditions, no thiophene was formed.
However, the use of thiourea in place of KSCN as a source of a
sulfide anion triggered the reaction toward thiophene
formation. A few 2-aryl substituted thiophenes were obtained
efficiently by the coupling of 1,3-dienyl bromides and thiourea
(Scheme 7).
Figure 1. ORTEP diagram of compound 4h.
Use of 4 equiv of KSeCN also produced the same result. These
diselanyl selenophenes are reported for the first time and may
be of potential for biological screening.
Scheme 7. Synthesis of Substituted Thiophenes by Coupling
of 1,3-Dienyl Bromides and Thiourea
a
Scheme 4. Synthesis of Alkyl-Substituted Selanyl
Selenophenes
a
Reaction conditions: 1,3-dienyl bromide (1 mmol), thiourea (1.2
mmol), CuO (20 mol %), DMF (2 mL), 110 °C, 16 h.
In summary, we have developed an efficient and general
protocol for the synthesis of chalcogenophenes, specifically
selenophenes and thiophenes in high yields by a simple one-pot
CuO nanoparticle-catalyzed coupling of 1,3-dienyl bromides
and potassium selenocyanide and thiourea, respectively. The
reaction of 1,3-dienyl gem-dibromides produced selanyl
selenophenes, a new class of organoselenocycles. This
procedure gives an easy access to a series of alkyl, aryl, and
heteroaryl substituted selenophenes and selanyl selenophenes,
and many of these molecules are reported for the first time. The
significant distinctive features of this reaction are use of
inexpensive CuO nanoparticles in place of expensive CuI14 as
the catalyst, KSeCN as the selenium source, and an
intramolecular nucleophilic cyclization of a selenium moiety
to an alkene unit. To the best of our knowledge we are not
aware of any such nucleophilic cyclization to selenophene.
We are currently investigating the mechanism of the reaction
and scope of this protocol for the synthesis of other molecules.
These results will be communicated in a full paper in due
course.
When 1,3-dienyl-1,3-dibromide (1n) underwent copper
catalyzed selenylation in the presence of excess KSeCN the
initially formed 2n underwent further reaction with KSeCN to
furnish a new selanyl selenophene, 3n (Scheme 5). The
formation of a similar intermediate was observed in the reaction
of 1,3-dienyl-gem-dibromide also (Scheme 6).
Scheme 5. Selenylation of 3-Bromo-1,3-dienyl Bromide
Scheme 6. Isolation of Intermediate during Formation of
Selanyl Selenophenes
ASSOCIATED CONTENT
* Supporting Information
■
S
In general, all the reactions are very clean and high yielding.
The pure products were obtained just by simple column
Typical experimental procedure and characterization data of all
1
products and copies of their H and 13C NMR spectra. This
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Letter
D.; Luchese, C.; Nogueira, C. W.; Zeni, G. J. Org. Chem. 2007, 72,
6726.
(14) Wu, B.; Yoshikai, N. Angew. Chem., Int. Ed. 2013, 52, 10496.
material is available free of charge via the Internet at http://
pubs.acs.org.
(15) CCDC 1004433.
(16) Gao, F.; Cheng, Y.; Yu, Q.; Liu, S.; Shi, D.; Li, Y.; Wang, P.
Inorg. Chem. 2009, 48, 2664.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: ocbcr@iacs.res.in.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are pleased to acknowledge the financial support from
DST, New Delhi through an award of JCB Fellowship to B.C.R.
(Grant No. SR/S2/JCB-11/2008). P.M. and D. K. thank CSIR
for their fellowships.
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