Potassium selenocyanate as an efficient selenium source in C-Se cross-coupling catalyzed by copper iodide in water

Article abstract of DOI:10.1016/j.tetlet.2011.05.068

An efficient and conceptually new protocol for C-Se cross coupling of potassium selenocyanate with aryl halides via copper-catalyzed cascade reaction has been developed in water. Utilizing this protocol, a variety of aryl and heteroaryl halides were reacted with potassium selenocyanate to afford the corresponding diaryl selenides in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2011.05.068

Tetrahedron Letters 52 (2011) 3978–3981
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Potassium selenocyanate as an efficient selenium source in C–Se
cross-coupling catalyzed by copper iodide in water
a
a
b
a,
⇑
A. Vijay Kumar , V. Prakash Reddy , C. Suresh Reddy , K. Rama Rao
a
Organic Chemistry Divison-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
Department of Chemistry, Sri Venkateswara University, Tirupati, India
b
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and conceptually new protocol for C–Se cross coupling of potassium selenocyanate with aryl
halides via copper-catalyzed cascade reaction has been developed in water. Utilizing this protocol, a vari-
ety of aryl and heteroaryl halides were reacted with potassium selenocyanate to afford the corresponding
diaryl selenides in moderate to good yields.
Received 28 February 2011
Revised 14 May 2011
Accepted 16 May 2011
Available online 20 May 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Aryl halides
Potassium selenocyanate
Diaryl selenides
Cross-coupling
Copper iodide
Water
Diaryl selenides have proven to be valuable building blocks in
organic synthesis and also serve as potential drug candidates.
Recently, organic reactions in water have attracted much
attention because water is the most economical, safe, non-toxic,
1
,2
3
Many compounds bearing this core unit have revealed diverse and
interestingbiological activities, such as antioxidant, antitumor, anti-
cancer, anti-infective, enzyme inhibiting, glutathione peroxidase
mimicking, immunomodulating etc.4 They have also been widely
used in chemo-, regio-, and stereoselective reactions and apart from
Table 1
a
Screening of copper catalyzed synthesis of diaryl selenides in water
5
this, selenium is known as a fundamental element in life sciences.
Entry
Copper source
Ligand
Base
Temp (°C)
Yieldb (%)
However, the classical version of this C-Se cross coupling reac-
tion requires photochemical or harsh reaction conditions, for
example, the use of polar and toxic solvents like HMPA and high
1
2
3
4
5
6
7
8
9
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
L1
L1
L1
L2
L3
L4
L5
L6
L4
L4
L4
L4
L4
L4
L1
—
CS
CS
CS
CS
CS
CS
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
3
3
3
3
3
3
rt
80
Trace
50
70
75
65
91
85
79
71
59
51
73
50
65
—
Trace
Trace
6
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
reaction temperatures. To overcome these drawbacks, transition
metals such as palladium, nickel,8 copper,9 iron, indium, and
7
10
11
1
2
lanthanum based catalytic systems have been studied for the
synthesis of diaryl selenides. These reactions usually involve the
coupling of aryl halides with either diaryl diselenides or aryl sele-
nols. Our recent report depicts the copper catalyzed synthesis of
diaryl selenides in excellent yields using selenourea as a selenium
source using DMSO as solvent.13 The majority of the reported pro-
tocols proceed in organic solvents and nowadays, their disposal is a
major problem for the chemical industry. Moreover, organic sol-
vents are expensive, toxic, flammable and not recyclable. Thus, it
is desirable to find a novel catalytic system for the synthesis of dia-
ryl selenides by using water as solvent.
CS CO3
2
CS
CS
CS
CS
2
CO
2
CO
2
CO
2
CO
3
3
3
3
Cu(OAc)
2
1
1
1
0
1
2
CuSO
CuI
CuI
CuI
CuI
—
4
Á5H
2
O
K
2
CO
3
13
KOH
PO
1
1
1
1
4
5
6
7
K
3
4
CS
CS
—
2
CO
CO
3
3
CuI
CuI
2
L4
a
Reactions and conditions: iodobenzene (1.0 mmol), potassium selenocyanate
1.2 mmol), catalyst (10 mol %), ligand (10 mol %), base (2.0 equiv), water (3.0 mL),
(
2
4 h, 100 °C
Isolated yield.
⇑
Corresponding author.
E-mail address: drkrrao@yahoo.com (K.R. Rao).
b
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.05.068

A. V. Kumar et al. / Tetrahedron Letters 52 (2011) 3978–3981
3979
NH2
NH2
NH2
the synthesis of diaryl selenides via C–Se cross coupling of potas-
sium selenocyanate with aryl halides catalyzed by copper iodide
in water. To the best of our knowledge, this is the first protocol ex-
plored for the synthesis of diaryl selenides via C–Se cross-coupling
of potassium selenocyanate with aryl halides catalyzed by CuI as a
catalyst in combination with trans 1,2-diaminocyclohexane as li-
HN
N
NH
N
N
N
NH
2
L1
L5
L2
CO H
L
L4
3
N
2
16
gand in water.
H
Initially, iodobenzene and potassium selenocyanate were chosen
as the model substrates to optimize the reaction conditions such as
various copper sources, bases, ligands and temperature (Table 1).
First, several catalysts and ligands were screened and CuI and L4
were proven to be preeminent for this cross coupling reaction (Ta-
L6
Scheme 1. Copper catalyzed synthesis of diaryl selenides in optimized conditions.
In all of the cases the cross-coupling of water.
2 3
ble 1, entry 6). The effect of bases was also investigated, and Cs CO
environmentally friendly and most readily available reaction med-
was foundto be most effectivein water(Table 1, entry 6). The control
experiment confirmed that the reaction did not occur in the absence
of catalyst (Table 1, entry 15) as well as the base (Table 1, entry 17).
Only trace amount of the expected product was formed in the ab-
sence of the ligand (Table 1, entry 16). The reaction when conducted
at room temperature and 80 °C, the yields observed were very low
1
4
ium. In the course of our continuing investigations in the field of
15
cross-coupling reactions we report, herein, a new approach for
Table 2
a
Copper catalyzed synthesis of symmetrical diaryl selenides in water
(Table 1, entries 1 and 2). The ideal temperature for the reaction
CuI, L4, H O
2
was found to be 100 °C. The best result was obtained when the reac-
tion was pursued at 100 °C using 10 mol % of the CuI/10 mol % of the
Ar
I
KSeCN
Ar Se Ar
0
2
4 h, 100 C
trans 1,2-diaminocyclohexane in the presence of Cs
2
CO
3
(2.0 equiv)
Entry
Arylhalides
Product
Yieldb (%)
in water Scheme 1.
1
2
3
4
I
Se
91
88
86
90
I
CuI/L4
Cs CO , water
Se
NH2
NH2
I
Se
Se
KSeCN
L4 =
2
3
O
1
00 C
I
MeO
I
I
MeO
Se
OMe
To explore the scope of this novel transformation, we examined
the cross-coupling of various substituted aryl iodides with potas-
sium selenocyanate. As shown in Table 2, different aryl iodides
were transformed into the corresponding diaryl selenides with
Se
5
82
O
2
N
O
2
N
NO
2
1
7,18
good isolated yields.
The results have shown that substitution
6
7
8
9
75
77
81
I
Se
O
N
I
O
N
Se
NO2
Table 3
2
2
Copper catalyzed synthesis of symmetrical diaryl selenides in watera
Br
Br
Br
CuI, L4, Cs CO
2
3
0
Ar
X
KSeCN
Ar Se Ar
I
Se
Se
Se
H O, 40 h, 100 C
2
Yieldb (%)
F
I
F
F
78
79
Entry
Arylhalides
Product
4
8
5c
1
1
1
0
1
Cl
I
Cl
Cl
1
2
3
4
Br
Cl
Se
Se
I
Se
61c
74
Trace
72
I
I
Se
Se
Br
Se
1
2
MeO
Br
Br
MeO
Se
OMe
79
N
N
S
N
Se
1
1
3
4
79
81
I
Se
S
S
5
65
N
N
S
N
I
Se
S
I
S
S
6
7
59
62
Br
S
Se
Se
S
1
1
5
6
77
76
S
S
Br
Br
Se
S
N
S
S
S
I
N
Se
N
N
Se
N
N
N
N
8
70
N
N
N
N
a
a
Reactions and conditions: aryl iodide (1.0 mmol), potassium selenocyanate
1.2 mmol), CuI (10 mol %), L4 (10 mol %) Cs CO (2.0 equiv), water (3.0 mL), 24 h,
00 °C.
Isolated yield.
Potassium selenocyanate (2.4 mmol).
Reactions and conditions: aryl halides (1.0 mmol), potassium selenocyanate
(
1
2
3
2 3
(1.2 mmol), CuI (10 mol %), L4 (10 mol %) Cs CO (2.0 equiv), water (3.0 mL), 40 h,
100 °C.
b
b
Isolated yield.
After 24 h.
c
c

3
980
A. V. Kumar et al. / Tetrahedron Letters 52 (2011) 3978–3981
X
X
SeCN
SeH
Se
KSeCN
CuI, L4
H O
2
Cs CO
2 3
CuI, L4/Cs CO3
2
Scheme 2. A plausible mechanism for the CuI catalyzed C–Se cross-coupling of aryl halides with potassium selenocyanate.
played a major role in governing the reactivity of the substrate.
This protocol efficiently coupled iodo benzenes having electron
donating groups (eg. Me, Et and OMe) with potassium selenocya-
nate to produce the corresponding products in good yields (Table 2,
entries 2, 3, 4), whereas in the presence of electron withdrawing
group (NO2) a slight decrease in the yield of the diaryl selenides
Silveira, C. C.; Rocha, J. B. T.; Wessjohann, L. A. Tetrahedron Lett. 2002, 43, 7329;
e) Braga, A. L.; Paixao, M. W.; Marin, G. Synlett 2005, 1975.
(a) Sarma, B. K.; Mugesh, G. Org. Biomol. Chem. 2008, 6, 965; (b) Nogueira, C. W.;
Zeni, G.; Rocha, J. B. T. Chem. Rev. 2004, 104, 6255; (c) Mugesh, G.; du Mont, W.
W.; Sies, H. Chem. Rev. 2001, 101, 2125; (d) Mugesh, G.; Singh, H. B. Chem. Soc.
Rev. 2000, 29, 347.
(
3
.
.
4
Engman, L.; Cotgreave, I.; Angulo, M.; Taylor, C. W.; Paine-Murrieta, G. D.;
Powis, G. Anticancer Res. 1997, 17, 4599.
(
Table 2, entries 6 and 7) was observed. Interestingly, when 1,2-
5. (a) Back, T. G.; Moussa, Z. J. Am. Chem. Soc. 2003, 125, 13455; (b) Anderson, C.
M.; Allberg, A.; Hogberg, T. Adv. Drug. Res. 1996, 28, 65; (c) Clark, L. C.; Combs,
G. F.; Turnbull, B. W., Jr.; Slate, E. H.; Chalker, D. K.; Chow, J.; Davis, L. S.; Glover,
R. A.; Graham, G. F.; Gross, E. G.; Krongrad, A.; Lesher, J. L.; Park, H. K., Jr.;
Sanders, B. B.; Smith, C. L., Jr.; Taylor, J. R. J. Am. Med. Assoc. 1996, 276, 1957; (d)
Woods, J. A.; Hadfield, J. A.; McGown, A. T.; Fox, B. W. Org. Biomol. Chem. 1993,
diiodobenzene was reacted with potassium selenocyanate, the de-
sired product was obtained in moderate yield (Table 2, entry 11).
Utilizing these conditions, heterocyclic compounds, such as 3-
iodopyridine and 2-iodo/5-methyl-2- iodo thiophene also afforded
the corresponding products in high yields (Table 2, entries 12–16).
In order to evaluate the scope of the process, a variety of substi-
tuted aryl bromides and chlorides were tested under the same
reaction conditions (Table 3). In the case of aryl bromides, the reac-
tion with potassium selenocyanate furnished the corresponding
diaryl selenide derivatives in moderate yields (Table 3 entries 1,
1
, 333.
6.
(a) Suzuki, H.; Abe, H.; Osuka, A. Chem. Lett. 1981, 151; (b) Osuka, A.; Ohmasa,
N.; Suzuki, H. Synth. Commun. 1982, 857; (c) Andersson, C. M.; Hallberg, A.;
Linden, M.; Brattsand, R.; Moldeus, P.; Cotgreave, I. Free Radical Biol. Med. 1994,
1
6
6, 17; (d) Andersson, C. M.; Hallberg, A.; Hugberg, T. Adv. Drug. Res. 1996, 28,
5.
7. Nishiyama, Y.; Tokunaga, K.; Sonoda, N. Org. Lett. 1999, 1, 1725.
8. Cristau, H. J.; Chabaud, B.; Labaudiniere, R.; Christol, H. Organometallics 1985, 4,
657.
3
–8) whereas in the case of aryl chlorides, trace amount of cou-
9.
(a) Bhadra, S.; Saha, A.; Ranu, B. C. J. Org. Chem. 2010, 75, 4864; (b) Singh, D.;
Alberto, E. E.; Rodrigues, O. E. D.; Braga, A. L. Green Chem. 2009, 11, 1521; (c)
Alves, D.; Santos, C. G.; Paixao, M. W.; Soares, L. C.; deSouza, D.; Rodrigues, O. E.
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Org. Biomol. Chem. 2009, 7, 1652; (e) Taniguchi, N.; Onami, T. J. Org. Chem. 2004,
pling product was observed (Table 3, entry 2).
Further more, C–Se cross-coupling of heterocyclic bromides
such as 3-bromopyridine, 5-methyl-2-bromothiopene and 5-bro-
mopyrimidine gave moderate to good yields (Table 3, entries 5–
6
9, 915; (f) Kumar, S.; Engman, L. J. Org. Chem. 2006, 71, 5400; (g) Taniguchi, N.
8
). Iodo benzene was found to be the more reactive substrate than
J. Org. Chem. 2007, 72, 1241; (h) Gujadhur, R. K.; Venkataraman, D. Tetrahedron
Lett. 2003, 44, 81; (i) Beletskaya, I. P.; Sigeev, A. S.; Peregudov, A. S.; Petrovskii,
P. V. Tetrahedron Lett. 2003, 44, 7039; (j) Wang, L.; Wang, M.; Huang, F. Synlett
bromo and chloro benzenes.
A plausible mechanism for the CuI catalyzed C–Se cross-cou-
pling of aryl halides with potassium selenocyanate is shown in
Scheme 2. First, the aromatic halide is activated by the Cu(I) com-
plex, which further reacts with potassium selenocyanate leading to
the formation of aryl selenocyanate. Then, aryl selenocyanate is
hydrolyzed to generate benzeneselenol under the basic conditions.
Then the newly generated benzeneselenol intermediate reacts
with the aryl halide in the presence of copper catalyst to afford
the C–Se coupling product.18
In conclusion, we have developed an experimentally simple and
inexpensive copper iodide catalyzed C–Se cross coupling of aryl ha-
lides with potassium selenocyanate as a selenium surrogate in
water without inert atmosphere. Various aryl halides underwent
cross-coupling with potassium selenocyanate to give the corre-
sponding products in high yields.
2005, 2007; (k) Chang, D.; Bao, W. Synlett 2006, 1786; (l) Taniguchi, N.; Onami,
T. Synlett 2003, 829; (m) Taniguchi, N. Synlett 2005, 1687.
1
1
1
0. Wang, M.; Ren, K.; Wang, L. Adv. Synth. Catal. 2009, 351, 1586.
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2. Murthy, S. N.; Madhav, B.; Reddy, V. P.; Nageswar, Y. V. D. Eur. J. Org. Chem.
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3. Reddy, V. P.; Kumar, A. V.; Rao, K. R. J. Org. Chem. 2010, 75, 8720.
4. (a)Organic Synthesis in Water; Grieca, P. A., Ed.; Blackie A & P: London, 1998; (b)
Lindstrom, U. M. Chem. Rev. 2002, 102, 2751; (c) Kobayahi, S.; Manabe, K. Acc.
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1
1
3
798.
5. (a) Reddy, V. P.; Swapna, K.; Kumar, A. V.; Rao, K. R. J. Org. Chem. 2009, 74, 3189;
b) Swapna, K.; Kumar, A. V.; Reddy, V. P.; Rao, K. R. J. Org. Chem. 2009, 74,
7514; (c) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org. Lett. 2009, 11,
1
1
1
(
9
1
51; (d) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org. Lett. 2009, 11,
697; (e) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Synlett 2009, 2783;
(
f) Reddy, V. P.; Kumar, A. V.; Rao, K. R. Chem. Lett. 2010, 39, 212; (g) Reddy, V.
P.; Kumar, A. V.; Rao, K. R. Tetrahedron Lett. 2010, 51, 3181.
6. Copper-catalyzed Cross-coupling reactions in aqueous media, see: (a) Teo, Y.-
C.; Chua, G.-L. Chem. Eur. J. 2009, 15, 3072; Teo, Y.-C.; Yong, F.-F.; Poh, C.-Y.;
Yan, Y.-K.; Chua, G.-L. Chem. Commun. 2009, 6258; Peng, J.; Ye, M.; Zong, C.; Hu,
F.; Feng, L.; Wang, X.; Wang, Y.; Chen, C. J. Org. Chem. 2011, 76, 716; Wang, F.;
Fu, H.; Jiang, Y.; Zhao, Y. Green Chem. 2008, 10, 452; Wang, Y.; Wu, Z.; Wang, L.;
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7. General procedure for the synthesis of diaryl selenides. Aryl halide (1.0 mmol), CuI
Acknowledgments
A.V.K. thanks UGC and V.P.R. thanks CSIR, New Delhi, for the
award of fellowship.
(
(
10 mol %), L4 (10 mol %), Cs
1.2 mmol) were charged in a 10 ml round bottom flask with a condenser
2 3
CO (2.0 equiv) and potassium selenocyanate
Supplementary data
under air, followed by the addition of water (3.0 mL). The reaction mixture was
heated in an oil bath at 100 °C and stirred at this temperature for 24 h. The
progress of the reaction was monitored by TLC. After the reaction was
complete, the reaction mixture was allowed to cool, and treated with ethyl
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.05.068.
2 4
acetate. The combined organic extracts were dried with anhydrous Na SO .
The solvent and volatiles were completely removed under vacuum to give the
crude product, which was purified by column chromatography on silica gel
References and notes
(
petroleum ether/ethyl acetate, 9:1) to afford the corresponding coupling
1 13
1
.
.
Krief, A.; Hevesi, L. Organoselenium Chemistry I; Springer: Berlin, 1988; (b)
Comasseto, J. V.; Ling, L. W.; Petragnani, N.; Stefani, H. A. Synthesis 1997, 373;
product in excellent yields. All the products were characterized by H and
NMR, MS and compared with the literature values.
C
(
c)Organoselenium Chemistry A Practical Approach; Back, T. G., Ed.; Oxford
University Press: Oxford, UK, 1999; (d) Procter, D. J. J. Chem. Soc., Perkin Trans. 1
000, 835.
Data of representative examples. Bis(4-ethylphenyl)selane (Table 2, entry 3). Light
À1
yellow oil; IR (neat):
m
3057, 2930, 2836, 1559, 1461, 1061, 937, 846, 735 cm
H NMR (200 MHz, CDCl
J = 8.12 Hz), 2.59 (q, 4H, J = 7.54 Hz), 1.22 (t, 6H, J = 7.54 Hz); C NMR (50 MHz,
CDCl , TMS): d = 133.0, 132.9, 128.8, 127.9, 28.4, 15.4; Mass (ESI): m/z 290
;
1
2
3
, TMS): d = 7.34 (d, 4H, J = 8.12 Hz), 7.06 (d, 4H,
13
2
(a) Braga, A. L.; Ludtke, D. S.; Vargas, F.; Braga, R. C. Synlett 2006, 1453; (b)
Braga, A. L.; Vargas, F.; Sehnem, J. A.; Braga, R. C. J. Org. Chem. 2005, 70, 9021; (c)
Braga, A. L.; Paixao, M. W.; Ludtke, D. S.; Silveira, C. C.; Rodrigues, O. E. D. Org.
Lett. 2003, 5, 3635; (d) Braga, A. L.; Silva, S. J. N.; Ludtke, D. S.; Drekener, R. L.;
3
[M+1]; Anal. Calcd for C16
6.19.
H18Se (289): C, 66.43; H, 6.27. Found: C, 66.37; H,

A. V. Kumar et al. / Tetrahedron Letters 52 (2011) 3978–3981
3981
Dinaphthalen-1-ylselane (Table 2, entry 5). Yellow liquid; IR (neat):
m
3
3091,
, TMS):
d = 8.05- 8.02 (m, 4H), 7.79–7.65 (m, 4H), 7.55- 7.40 (m, 4H), 7.15 (t, 2H,
J = 7.93 Hz); 13C NMR (50 MHz, CDCl
, TMS): d = 137.2, 133.9, 131.9, 128.8,
28.3, 127.5, 126.6, 125.6; Mass (ESI): m/z 335[M+1]; Anal. Calcd for C20 14Se
334): C, 72.07; H, 4.23. Found: C, 72.01; H, 4.18.
Calcd for C12
H
8
Br
2
Se (390): C, 36.87; H, 2.06. Found: C, 36.81; H, 1.99.
3092, 2960,
, TMS): d = 7.51(s,
, TMS): d = 132.9, 129.0, 127.5; Mass
Se (238): C, 40.52; H, 2.55; N,
À1
1
2
928, 1588, 1390, 1077, 968, 848 cm
;
H NMR (200 MHz, CDCl
Dipyrimidin-5-ylselane (Table 3, entry 8). Colorless oil; IR (neat): m
À1
1
1597, 1444, 1068, 865, 738 cm
;
H NMR (200 MHz, CDCl
2H), 7.25(s, 4H); C NMR (50 MHz, CDCl
(ESI): m/z 239 [M+1]; Anal. Calcd for C
23.63. Found: C, 40.46; H, 2.45; N, 23.57.
3
13
3
3
1
(
H
8 6 4
H N
Bis(3-bromophenyl)selane (Table 2, entry 7):Colorless oil; IR (Neat):
m
3
3062,
, TMS):
, TMS):
18. (a) Ke, F.; Qu, Y.; Jiang, Z.; Li, Z.; Wu, D.; Zhou, X. Org. Lett. 2011, 13, 454; (b)
À1
1
3
2
857, 1599, 1443, 1042, 910, 823, 746 cm
;
H NMR (200 MHz, CDCl
Tao, C.; Lv, A.; Zhao, N.; Yang, S.; Liu, X.; Zhou, J.; Liu, W.; Zhao, J. Synlett 2011,
134.
1
d = 7.31–7.12 (m, 6H), 6.99–6.93 (m, 2H); C NMR (50 MHz, CDCl
3
d = 164.6, 161.2, 130.6, 128.6, 119.9, 114.7; Mass (ESI): m/z 391 [M+1]; Anal.