Palladium-catalyzed phenyl-selenylation with n-Bu3SnSePh in one-pot two-step reactions

Article abstract of DOI:10.1016/j.tetlet.2006.03.106

We have studied the Pd-catalyzed cross-coupling reaction of a stannane derived from selenium n-Bu₃SnSePh (1) with aryl and perfluoroalkyl iodides. Herein a very efficient one-pot two-step selenylation reaction to form a C-Se bond is reported. Ph₂Se₂ reacts with Na metal in liquid ammonia yielding PhSe^- ions. To this solution n-Bu₃SnCl was added to afford 1, which was introduced in the palladium-catalyzed coupling reaction without isolation. These reactions afford functionalized diarylselenides and phenylperfluroalkyl selenides from good to high yields (38-98%).

Full text of DOI:10.1016/j.tetlet.2006.03.106

Tetrahedron Letters 47 (2006) 3511–3515
Palladium-catalyzed phenyl-selenylation with n-Bu3SnSePh
in one-pot two-step reactions
*
*
´
Mariana Bonaterra, Sandra E. Martın and Roberto A. Rossi
INFIQC, Departamento de Quı´mica Orga´nica, Facultad de Ciencias Quı´micas, Universidad Nacional de Co´rdoba,
Co´rdoba 5000, Argentina
Received 20 February 2006; revised 14 March 2006; accepted 15 March 2006
Available online 5 April 2006
Abstract—We have studied the Pd-catalyzed cross-coupling reaction of a stannane derived from selenium n-Bu3SnSePh (1) with aryl
and perfluoroalkyl iodides. Herein a very efficient one-pot two-step selenylation reaction to form a C–Se bond is reported. Ph2Se2
reacts with Na metal in liquid ammonia yielding PhSeꢀ ions. To this solution n-Bu3SnCl was added to afford 1, which was intro-
duced in the palladium-catalyzed coupling reaction without isolation. These reactions afford functionalized diarylselenides and
phenylperfluroalkyl selenides from good to high yields (38–98%).
Ó 2006 Elsevier Ltd. All rights reserved.
Transition metal-catalyzed reactions of aryl halides or
triflates with organoheteroatom compounds are widely
used for the synthesis of different heteroatom-contained
compounds.1 Organotin compounds are extensively
used in cross-coupling reactions.2 Although organo-
stannanes having a Sn–Se bond are known, the synthetic
applications of these organostannylselenides are few.2g
The biological and medicinal roles of organoselenium
compounds are progressively more important due to
their antioxidant, antitumor, antimicrobial, and antivi-
ral properties.3 Ar2Se in particular have attracted con-
siderable attention and several synthetic methods are
available for their synthesis.4 In addition, Ar2Se can be
obtained by coupling of ArI catalyzed by Ni(II)5 or by
Cu(I).6 However, most of these methods require the
handling of unstable reagents and a two-step procedure.
A relative new alternative includes organostannylsele-
nides, since it has been shown that the trialkylstannyl-
arylselenides (R3SnSeAr) are an excellent source of
arylselenyl groups.7 The reason for this is that they are
more convenient to handle than most commonly used
selenols because of their stability to air and moisture.
Approaches to the preparation of R3SnSeAr from
distannane (R3Sn)2 and diselenide (RSe)2,8 or by the
reaction of R3SnCl with PhSeNa were described.9
R3SnSeAr were also used as a source of a arylselenyl
group in the arylselenylation of aryl halide and/or tri-
flates catalyzed by Pd,10,11 Ni,12 and Cu.13 Recently,
Pd pincer-complexes were used in selenylation of
organohalides.14
Herein, we report our results on the Pd-catalyzed cross-
coupling reaction of n-Bu3SnSePh (1) with ArI in one-
pot two-step reactions to form unsymmetric diaryl
selenides. The in situ generation of the n-Bu3SnSePh
eliminates the tedious isolation and purification of the
tin reagent. To extend the applications of this method-
ology, we studied the Pd-catalyzed cross-coupling
reaction of 1 with perfluoroalkyl iodides (RfnI). To
the best of our knowledge, this is the first report of the
Pd(0) catalyzed reaction for heteroatom–Rfn bond
formation. Only the introduction of a Rfn group on
olefinic and acetylenic carbons by the Pd-catalyzed
reaction between organotin and RfnI was reported.15
Synthetic routes to perfluoroalkyl aryl selenides are
not numerous.16 Recently, aryl and alkyl perfluoroalkyl
selenides were obtained from diselenides in the presence
of sodium hydroxymethanesulfinate from fair to good
yields (28–80%).17 Perfluoroalkyl selenylation of olefins
has also been performed.18
Keywords: Organostannylselenides; Selenylation; Pd catalysis; Perfluo-
roalkyl iodides.
Concerning the Pd-catalyzed cross-coupling reaction
of 1 with ArI, the generation and subsequent use of 1
was in accordance with the procedure previously
*
Corresponding authors. Tel.: +54 351 4334170; fax: +54 351
4333030; e-mail: rossi@mail.fcq.unc.edu.ar
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.106

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M. Bonaterra et al. / Tetrahedron Letters 47 (2006) 3511–3515
reported by us for the synthesis of tertiary phosphanes,2e
arsanes, and stibanes2h by Pd-catalyzed reaction of the
corresponding organotin reagents. A typical procedure
involves the formation of PhSeꢀ anions from Ph2Se2
(1 mmol) and Na metal (2 mmol) in liquid ammonia
(Eq. 1), then n-Bu3SnCl (2 mmol) was added to obtain
1 (Eq. 2). The ammonia was allowed to evaporate and
the organic solvent was added. The Pd-catalyzed cross-
coupling reaction was performed with the solution of 1
and the ArI (1.4 mmol) in the presence of (PPh3)2PdCl2
(1.5 mol %) (Eq. 3).
to the cross-coupling reaction in DMF at 120 °C, the
system became more efficient giving 7b in moderate yield
(entry 12). Apparently, a more polar solvent as DMF
may not only favor the selenylation through a faster oxi-
dative addition, but also increase the solubility of CsF.21
This still low yield may be due to a tendency of the
hydroxy group to coordinate the Pd metal or the intrin-
sic acidity of the phenol group, thus reducing its activity
and/or retarding the transmetalation. To further opti-
mize the reaction, we carried it out protecting this group
as an acetoxy. Initially, in the reaction of 4-iodophenyl
acetate (8a) with 1 conducted at 80 °C in toluene, the
hydrolyzed product 7a was formed in 25% yield and
75% of the substrate was recovered (entry 13). In the
presence of CsF, the reaction of 8a provided the cou-
pling product with deprotection of the hydroxyl group
7b in low yield, with a similar ratio of the coupling pro-
tective product (entry 14). The yields improved when
PPh3 was added as ancillary ligand (entry 15). When
examining the possibility that added phosphanes
increase yields, four different reaction conditions could
be considered: nonpolar solvent with or without added
phosphane, and polar solvent with or without added
phosphane. We have already examined the first two of
these conditions. When the reaction of 8a was carried
out in DMF at a higher temperature, with CsF, only
10% yield of 7b was obtained (entry 17). However, in
the presence of CsF and PPh3, 7b was obtained in 95%
yield (entry 18). In conclusion, the yield increase resulted
from a combination of the change of the solvent and the
addition of phosphane. Also, under these conditions, the
catalyst system was more effective and the cross-cou-
pling reaction appeared to be faster than the deprotec-
tion of the 8a. The electron-withdrawing and reducible
4-iodonitrobenzene (9a) was found to be compatible
with these selenylation conditions, and reduction prod-
ucts of the substrate were not observed. When we
attempt the reaction of 9a in toluene at 80 °C, the reac-
tion did not proceed (entry 18). The use of PPh3 and
CsF in DMF allowed the reaction to proceed; however,
9b was obtained in only 38% yield (entry 19). In sum-
mary, there are two different general conditions for the
cross-coupling reaction with ArI and 1. For ArI with
electron-withdrawing groups, the reactions proceeded
to high yields in toluene at 80 °C. On the other hand,
ArI with electron-donating groups required the use of
PPh3 and CsF in DMF at 120 °C to give comparable
yields.
2 Na
Ph2Se2
2 PhSe
NH3
ð1Þ
ð2Þ
ð3Þ
NH3
n-Bu3SnCl
n-Bu3SnSePh
PhSe
1
PhMe
Pd(0)
1 + ArI
PhSeAr
PhMe
The results of the Pd-catalyzed selenylation with ArI are
presented in Table 1. The reaction of 1 with 1-iodonaph-
thalene (2a) catalyzed by (PPh3)2PdCl2, afforded the
1-naphthylphenylselenide (2b) with total selectivity in
94% yield within 24 h (entry 1). By contrast, when the
procedure was carried out without the Pd catalyst, there
was almost no reaction (entry 2). By performing the
reaction with only PhSeꢀ anions without 1, we found
only 8% of product 2b (entry 3). When 4-chloroiodo-
benzene (3a) was allowed to react, the selenide 3b was
obtained in 96% yield (entry 4). The redox-sensitive aryl
iodide 4a, bearing a carbonyl group, was directly trans-
formed into the selenide 4b in high yields (entry 5).
4-Methoxyiodobenzene (5a) did not react under the
conditions above described (entry 6). Lewis-basic addi-
tives have been shown to facilitate certain Stille reac-
tions, presumably by generating hypervalent stannane
complexes.19 Considering this and the fact that the addi-
tion of Fꢀ ions could provide a more efficient cross-cou-
pling reaction, we used CsF as an activator of the
organotin reagent.20 In the presence of 3 equiv of CsF,
the cross-coupling reaction of substrate 5a produced sel-
enide 5b in good yields (entry 7). The transformation of
the 4-iodoaniline (6a) to the selenide 6b was successfully
carried out. When the reaction was performed in toluene
at 100 °C (entry 8), the yields of selenide 6b were lower
(50%) but they improved at a higher temperature (entry
9). It should be noticed that, in the cross-coupling selen-
ylation carried out by Beletskaya et al.,11 no reaction
occurs with 6a, and Sonoda et al. reported lower yields
with this substrate in a related system.10 When 4-iodo-
phenol (7a) was allowed to react with 1 in toluene at
80 °C, the yield of the diarylselenide 7b was only 6% (en-
try 10). With the addition of 3 equiv of CsF, we found
that the reaction provided the product 7b with 15% yield
(entry 11). The observation of an important ligand effect
in the Stille reaction, and in particular the catalytic
activity displayed by a Pd catalyst employing phos-
phanes as ancillary ligands,2a encouraged us to under-
take the reaction with PPh3 as ligand. When PPh3 (4:1
with respect to the catalyst) and also CsF were added
Next, we turned our attention to the cross-coupling of 1
with RfnI. In an initial attempt, we performed the reac-
tion of 1 with perfluorooctyl iodide (10a) (Eq. 4) whose
results are shown in Table 2. It was found that, although
the reaction did not proceed in toluene at 80 °C, when
CsF and 10 mol % of the catalyst were added we
obtained 10% yield of 10b (entries 1 and 2). Adding
PPh3 as ligand the results did not improve (entry 3).
However, with 3 equiv of CsF, 10b was formed in 30%
yield (entry 4). Using DMF as solvent and at a higher
temperature the selenylation reaction proceeded in a
similar way as in toluene (entry 5). Nevertheless, the
use of 10 mol % of the catalyst led to a significantly
more active catalyst system, allowing the reaction to

M. Bonaterra et al. / Tetrahedron Letters 47 (2006) 3511–3515
3513
a
Table 1. Selenylation of ArI with 1 in the presence of (PPh3)2PdCl2
(PPh3)2PdCl2
n-Bu3SnSePh
FG
I
FG
SePh
+
PhMe or DMF
Ph3P, CsF
1
FG = Cl, COMe, OMe, NH2, OH, OCOMe, NO2
Entry
Substrate
Conditions
Product
Yield (%)b
I
Se
1
2
3
Toluene (80 °C)
94
5
8
2a
Without catalyst
2b
Without 1c
Se
4
5
3a
4a
Toluene (80 °C)
Toluene (80 °C)
3b
4b
96
Cl
I
Cl
Se
I
C
O
H C
3
98 (92)
H3C
C
O
Se
6
7
Toluene (80 °C)
—
83
5a
6a
5b
6b
MeO
I
Toluene (80 °C), CsFd
MeO
Se
8
9
Toluene (100 °C)
Toluene (116 °C)
50
78
H2N
I
H2N
Se
10
11
12
Toluene (80 °C)
6
15
50
Toluene (80 °C), CsFd
DMF (120 °C), CsF, PPh3
7a
7b
HO
I
e
HO
HO
13
14
15
16
17
Toluene (80 °C)
7a
7b
7a: 25
7b: 19
7b: 38
7b: 10
7b: 95
I
Toluene (80 °C), CsFd
O
f
8a
Se
Toluene (80 °C), CsF, PPh3
DMF (120 °C), CsFd
MeCO
I
HO
f
DMF (120 °C), CsF, PPh3
Se
18
19
Toluene (80 °C)
DMF (120 °C), CsF, PPh3
9b
—
38
9a
O N
2
I
e
O2N
a Reaction conditions: PhSeꢀ anion was prepared in 300 mL of liquid ammonia from Ph2Se2 (1 mmol) and Na metal (2 mmol) and then n-Bu3SnCl
(2 mmol) was added. The coupling reaction was carried out with the aryl halide (1.4 mmol) and (PPh3)2PdCl2 (1.5 mol %) for 24 h.
b CG yields. Isolated yields in branches. The other selenides were isolated with yields ca. 10–15% lowers than the CG ones. These yields were not
optimized.
c Reaction was carried out without adding n-Bu3SnCl.
d 3 equiv of CsF were added.
e The coupling reaction was carried out with the ArI (1.0 mmol), (PPh3)2PdCl2 (5 mol %), CsF (3.0 mmol), and PPh3 (Pd–L, 1:4) for 24 h. Without
the addition of CsF and PPh3 there were not reaction and 85% of the reduction product.
f The coupling reaction was carried out with the ArI (1.4 mmol) and (PPh3)2PdCl2 (5 mol %), CsF (4.2 mmol), PPh3(Pd:L, 1:4).
proceed to 70% yield (entry 6). Likewise, the Pd-cata-
lyzed selenylation of the perfluorodecyl iodide (11a) with
1 could be successfully carried out. PhSeC10F21 (11b)
was obtained in 90% yield (entry 7). To the best of
our knowledge, this is the first example of the synthesis
of PhSeRfn by Pd-catalyzed cross-coupling reaction and
also the first report of a reaction for heteroatom–Rfn
bond formation using RfnI as electrophiles.

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M. Bonaterra et al. / Tetrahedron Letters 47 (2006) 3511–3515
Table 2. Pd-catalyzed cross-coupling of 1 with RfnI as electrophilea
Entry
Substrate
(PPh3)2PdCl2 (mol %)
Solvent
Ligand:PPh3 (Pd:L)
Additive: CsF (equiv)
Product
Yield (%)
1
2
3b
4
5
6
7
10a
10a
10a
10a
10a
10a
11a
l.5
10
10
10
1.5
10
Toluene
Toluene
Toluene
Toluene
DMF
—
—
—
1.1
1.1
3
3
3
10b
10b
10b
10b
10b
10b
11b
<2
10
7
30
35
70
90
1:4
1:4
1:4
1:4
1:4
DMF
DMF
10
3
a Reaction conditions: PhSeꢀ ion was prepared in 300 mL of liquid ammonia from Ph2Se2 (1 mmol) and Na metal (2 mmol) and then n-Bu3SnCl
(2 mmol) was added. The coupling reaction was carried out with RfnI (1.4 mmol) and (PPh3)2PdCl2 for 24 h at 80 °C when toluene was used and
120 °C when DMF was used.
b CG yields.
(PPh3)2PdCl2
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PhSeRfn
n-Bu3SnSePh
RfnI
+
ð4Þ
Rfn = C8F17 10a
C10F21 11a
10b
11b
´
R. A.; Martın, S. E. Coord. Chem. Rev. 2006, 250, 575–
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In conclusion, we have reported a very efficient one-pot
two-step selenylation by Pd-catalyzed cross-coupling
reaction to obtain a wide range of functionalized
organoselenides. This methodology has some notable
features: (i) the use of a stable organoselenium reagent
against air and moisture; (ii) the feasibility of a one-
pot reaction; (iii) a high yield preparation method of
functionalized aryl selenides; (iv) a high functional
group compatibility. Particularly noteworthy is the fact
that perfluoroalkyl iodides were viable electrophiles in
the Pd-catalyzed cross-coupling and that the synthesis
of PhSeRfn by this reaction proved a new versatile tool.
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Rossi, R. A.; Pierini, A. B.; Penenory, A. B. Chem. Rev.
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Acknowledgments
´
We would like to thank Agencia Cordoba Ciencia,
CONICET, FONCYT and SECYT, Universidad Nac-
ional de Cordoba for their continuous support to our
work in this area. M.B. thanks CONICET for the
fellowship.
´
7. Nishiyama, Y.; Sonoda, N. Mini-Rev. Org. Chem. 2005, 2,
147–155.
Supplementary data
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1999, 1, 1725–1727.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.03.106.
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