Indium-mediated mild and efficient one-pot synthesis of alkyl phenyl selenides

Article abstract of DOI:10.1016/j.tetlet.2005.10.025

A mild and convenient one-pot process for synthesizing alkyl phenyl selenides is developed using indium metal. The reaction shows the selectivity for tert-alkyl, benzylic, and allylic halides over primary and secondary alkyl halides.

Full text of DOI:10.1016/j.tetlet.2005.10.025

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8769–8771
Indium-mediated mild and efficient one-pot synthesis
of alkyl phenyl selenides
Wanida Munbunjong,c Eun Hwa Lee,a Warinthorn Chavasiric,* and Doo Ok Janga,b,
*
aDepartment of Chemistry, Yonsei University, Wonju 220-710, Republic of Korea
bCenter for Bioactive Molecular Hybrids, Yonsei University, Seoul 120-749, Republic of Korea
cDepartment of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
Received 13September 2005; revised 6 October 2005; accepted 11 October 2005
Available online 26 October 2005
Abstract—A mild and convenient one-pot process for synthesizing alkyl phenyl selenides is developed using indium metal. The reac-
tion shows the selectivity for tert-alkyl, benzylic, and allylic halides over primary and secondary alkyl halides.
Ó 2005 Elsevier Ltd. All rights reserved.
Organic selenides have been playing an important role
in organic synthesis.1 They have been employed widely
as key intermediates for introducing new functional
groups. For instance, phenyl selenides generally have
been used as precursors for forming carbon–carbon
double bonds. Although a number of research reports
on the preparation of organoselenides have been pub-
lished,1,2 they have several drawbacks including the
instability of reagents used and the strongly acidic or
basic reaction conditions.3 Therefore, a method of pre-
paring organoselenides with stable reagents under neu-
tral conditions is still called for.
In
+
R-X
PhSeSePh
R-SePh
CH2Cl2, reflux
Scheme 1.
Table 1. Reaction of tBuCl with PhSeSePh (1 equiv) in the presence of
indium
In (1 equiv)
tBuCl + PhSeSePh
tBuSePh
CH2Cl2, reflux
Entry tBuCl (equiv) In (equiv) Temp Time (h) Yield (%)a
1
2
32.0
4
5
6
2.0
2.0
1.0
1.0
Reflux
rt
1
Reflux
Reflux
Reflux
1
399
95
Recently, indium metal has drawn an increasing atten-
tion for its unique properties such as low toxicity and
high stability in water and air compared with other
metals.4 As part of our effort toward developing applica-
tions of indium metal in organic synthesis,5 we pro-
vided an indium-mediated reaction for the preparation
of organoselenides. We report on a mild and efficient
one-pot procedure for the synthesis of alkyl phenyl
selenides using indium metal under neutral conditions
(Scheme 1).
0
Reflux
0
2.0
2.0
2.0
1.0
0.1
1.0
t
1
1
1
73b
20
3c
a Analyzed by GC based on BuCl.
b 0.2 equiv of I2 was added.
c 1.0 equiv of InCl3 was used instead of In.
tBuCl in the presence of an equimolar amount of indium
t
We first investigated the reaction of BuCl with PhSe-
in CH2Cl2 at reflux for 1 h, tert-butyl phenyl selenide
SePh under several reaction conditions (Table 1). When
diphenyl diselenide was allowed to react with 2 equiv of
t
was obtained in 95% yield based on BuCl (entry 1).
At room temperature, longer reaction time was required
to complete the reaction (entry 2). In the absence of
indium metal, the reaction did not proceed at all, which
implies that indium was a promoter of the reaction
(entry 3). The addition of a catalytic amount of iodine
caused a decrease in the yield of alkyl phenyl selenides
Keywords: Indium; Alkyl phenylselenides; Diphenyl diselenide; Alkyl
halides.
*
Corresponding authors. Tel.: +82 337602261; fax: +82 337602208
(D.O.J.); e-mail: dojang@dragon.yonsei.ac.kr
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.025

8770
W. Munbunjong et al. / Tetrahedron Letters 46 (2005) 8769–8771
t
Table 2. Solvent effects on the reaction of BuCl with PhSeSePh
alkyl halides underwent a clean reaction to provide the
corresponding alkyl phenyl selenides in high yields
(entries 1–6). It is noteworthy that the reaction of tert-
alkyl halides with metal phenyl selenoates could not
be achieved even under harsh reaction conditions.3c Pri-
mary and secondary alkyl iodides showed high reactivity
under these conditions (entries 7 and 8). On the other
hand, primary and secondary alkyl bromides remained
inactive (entries 9 and 10). Although the reactivity of
aryl halides was very low (entry 15), benzylic and allylic
halides were converted into the corresponding sele-
nides in excellent yields (entries 11–14). Next, we applied
the method to preparing alkyl phenyl chalcogenides.
In (1 equiv)
tBuCl
(2 equiv)
Solvent
+
PhSeSePh
(1 equiv)
tBuSePh
solvent, reflux, 1 h
Yield (%)a
Benzene
Toluene
THF
ClCH2CH2Cl
CH3CN
65
41
22
52
66
95
42
CH2Cl2
CH2Cl2–H2O (9:1, v/v)
a Analyzed by GC based on BuCl.
t
t
Treatment of BuCl with PhSSPh or PhTeTePh in the
presence of indium in CH2Cl2 at reflux gave the corre-
sponding sulfide and telluride in 35% and 95% yields,
respectively.
(entry 4).6 With a catalytic amount of indium or 1 equiv
of InCl3 the reaction was not efficient (entries 5 and 6).
Recently, there have been reports that alkyl radicals are
readily generated from alkyl halides by indium metal
and are added to electron-deficient carbon–carbon dou-
ble bonds.5c,7 Compared with primary alkyl halides, ter-
tiary alkyl halides showed high reactivity under the
present reaction conditions (Table 2). We carried out
some competitive experiments with mixtures of tertiary
alkyl halides. A set of mixture of tert-butyl halides was
treated with indium metal in CH2Cl2 at reflux for
15 min, and analyzed the remaining tert-butyl halides.
The ratio of the remaining tert-butyl halides as Cl–I,
Cl–Br, and Br–I was 6.5:1, 3.6:1, and 2.6:1, respectively.
Thus, the relative reactivity of halides was found to fol-
low the sequence: I > Br > Cl. It is consistent with the
order of halides with respect to the reactivity under radi-
cal reaction conditions. On the basis of these findings, it
might be assumed that there is a possibility of not only
involving metal selenoates as suggested for the reaction
using La or Zn, but also radical intermediates.
Next, we examined the solvent effects of the reaction
(Table 2). The reaction of tBuCl with PhSeSePh in com-
mon organic solvents such as benzene, toluene, THF,
ClCH2CH2Cl, and CH3CN gave tert-butyl phenyl sele-
nide in low to moderate yields. The reaction performed
in CH2Cl2 was the most efficient affording a 95% yield of
tert-butyl phenyl selenide. In aqueous CH2Cl2, the yield
of the product decreased.
With the optimal conditions in our hand, we investi-
gated the scope and limitations of the present method
employing a variety of sterically different organic
halides. The results are summarized in Table 3. Tertiary
Table 3. Reaction of various alkyl halides with PhSeSePh in the
presence of indium
In (1 equiv)
RX
+
PhSeSePh
RSePh
CH2Cl2, reflux, 1 h
(2 equiv)
(1 equiv)
The reaction pathway for the formation of alkyl phenyl
selenides is illustrated in Scheme 2. First, indium metal
reduced alkyl halides to generate alkyl radicals, and then
the SH2 reaction of alkyl radicals with diphenyl disele-
nide formed alkyl phenyl selenides. The PhSeInX species
that was generated during the reaction reacted with
other alkyl halide through SN2 pathway to give the cor-
responding alkyl phenyl selenides.
Entry
RX
Yield (%)a
1
2
3
4
5
6
7
8
9
tBuI
tBuBr
tBuCl
1-Iodoadamantane
1-Bromoadamantane
1-Chloroadamantane
iPrI
99
95 (86)
95
86 (76)
84 (74)
90 (88)
98 (70)
98 (78)b
Traceb
CH3(CH2)15
Cyclohexyl bromide
I
In conclusion, we have developed a mild and efficient
one-pot method for synthesis of alkyl phenyl selenides
by indium-mediated reaction of diphenyl diselenide with
organic halides, which showed the selectivity for tert-
alkyl, benzylic, and allylic halides over primary and
secondary alkyl halides. Our method has some advanta-
ges including a simple experimental procedure, the
10
Traceb
C6H11
Br
Br
11
98 (85)
Br
Br
12
99 (95)
Br
R
RX + In
+ InX
I
13
14
99 (89)
97 (73)
Br
PhSeSePh
15
PhBr
Trace
RX
a Analyzed by GC based on alkyl halides. The yields in parenthesis are
isolated yields.
b The reaction time was 3h.
RSePh + InX2
RSePh
+ PhSeInX
Scheme 2.

W. Munbunjong et al. / Tetrahedron Letters 46 (2005) 8769–8771
8771
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A typical experimental procedure is as follows: Indium
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This work was supported by Center for Bioactive
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thankful to Thailand Research Fund for the 2004 Royal
Golden Jubilee Ph.D. research assistant fellowship.
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