Efficient synthesis of diorganyl selenides via cleavage of Se-Se bond of diselenides by indium(III) catalyst and zinc

Article abstract of DOI:10.1016/j.tetlet.2006.07.148

A simple and efficient procedure for the synthesis of unsymmetrical diorganyl selenides from an one-pot indium(III) catalyzed procedure, in the presence of zinc, has been developed. Various organic halides and even the unreactive organic chlorides underwe

Full text of DOI:10.1016/j.tetlet.2006.07.148

Tetrahedron Letters 47 (2006) 7195–7198
Efficient synthesis of diorganyl selenides via cleavage of Se–Se
bond of diselenides by indium(III) catalyst and zinc
Antonio L. Braga,a,* Paulo H. Schneider,b Marcio W. Paixaoa and Anna M. Deobalda
˜
aDepartamento de Quı´mica, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil
bInstituto de Quı´mica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Received 22 June 2006; revised 25 July 2006; accepted 28 July 2006
Available online 22 August 2006
Abstract—A simple and efficient procedure for the synthesis of unsymmetrical diorganyl selenides from an one-pot indium(III) cat-
alyzed procedure, in the presence of zinc, has been developed. Various organic halides and even the unreactive organic chlorides
underwent the reaction efficiently. Also diaryl and dialkyl diselenides underwent the coupling reaction.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
applications in synthetic organic chemistry: for example,
in ring opening of epoxides and aziridines,9 Diels–Alder
cycloadditions,10 reductive Friedel–Crafts alkylations11
or thioacetalization of aldehydes and ketones.12
During the last five decades, selenium compounds have
played an important role in organic chemistry, acting as
versatile reagents in organic synthesis1 and catalysis.2
The biological and medicinal properties of selenium
and organoselenium compounds is also increasingly
appreciated, mainly due to their antioxidant, antitumor,
antimicrobial, and antiviral properties.3 Besides, the
synthesis of peptides containing selenocysteine is rapidly
gaining interest with the discovery of an increasing num-
ber of proteins containing this amino acid.4
Recently, we reported the synthesis of a new set of
chiral a-seleno-amines in a straightforward manner
through the stereoselective aziridine ring opening with
indium(III)-chalcogenolates, obtained from indium(I)
iodide and diorganoyl diselenides.13 Attempting to
disclose further applications of indium salts, we examine
here the application of a bimetallic (In(III)/Zn) system,
in the generation of selenolate anions. The coupling
in situ with organic halides gave the corresponding
diorganoyl selenides (Scheme 1).
The development of new methods for the introduction
of selenium-containing groups into organic molecules
remains a significant challenge,5 specially the prepara-
tion of unsymmetrical diorganyl selenides.6 In general,
to avoid handling unstable reagents, such as selenols,
diorganyl diselenides are used as starting materials and
the selenium anion is generated in situ via chemical
Se–Se bonds reduction. However, this procedure often
requires drastic reaction conditions, such as reduction
with hydrides,7 which reduces the possibility of some
functionality or more complex substrates to be present.
Our idea was to develop a simple experimental proce-
dure, with a catalytic system easy to handle, less expen-
sive than those with indium(I) and active enough to
promote the direct coupling of diselenides and organic
halides.14 The work resulted in an efficient synthesis of
diorganyl selenides derivatives under mild and neutral
conditions.
The experiments were initially conducted with 1-bro-
mododecane and the phenyl selenolate anion, prepared
On the other hand, indium metal and its salts have been
the subject of continued interest because of their
remarkable efficiency in various synthetic operations.8
Particularly, indium(III) halides have found successful
2.5 - 10 mol % InX3
2RSeR'
RSeSeR
+ 2R'X
Zn, DMF, 100 °C
*
Corresponding author. Tel.: +55 55 32208761; fax: +55 55
32208998; e-mail: albraga@quimica.ufsm.br
Scheme 1. General synthesis of diorganyl selenides.
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.148

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A. L. Braga et al. / Tetrahedron Letters 47 (2006) 7195–7198
Table 1. In-Catalyzed Zn-mediated reaction of diphenyl diselenide with 1-bromododecane
Zn/ InX3
CH3(CH2)10CH2Br
CH3(CH2)10CH2 SePh
PhSeSePh
+
Solvent, 1h
Entry
Solvent
InX3 (mol %)
Yielda (%)
1
2
3
4
5
6
7
8
9
DMF (100 ꢁC)
DMF (100 ꢁC)
DMF (100 ꢁC)
THF (Reflux)
CH2Cl2 (Reflux)
CH3CN (Reflux)
DMF (100 ꢁC)
DMF (100 ꢁC)
DMF (100 ꢁC)
InBr3 (10)
InBr3 (5)
100
98
98
25
20
30
96
94
88
InBr3 (2.5)
InBr3 (2.5)
InBr3 (2.5)
InBr3 (2.5)
InCl3 (2.5)
InOTf3 (2.5)
InCl3Æ4H2O (2.5)
a Yields refer to those of pure isolated products characterized by spectroscopic methods.
through the reaction between PhSeSePh and Zn/InX3 to
establish the best reaction conditions (Table 1). At first,
the reaction was carried out with InBr3 (10 mol %) as
the catalyst and DMF as the solvent (Table 1, entry 1).
Decrease in the catalyst loading from 10 mol % to
2.5 mol %, does not have influence in the reaction, fur-
nishing the corresponding diorganyl selenolate in quanti-
tative yields (Table 1, entries 1–3). Other solvents proved
to be less effective for the chemical efficiency of the reac-
tion. Changing the solvent from DMF to THF, CH2Cl2
or acetonitrile, causes a drastic decrease in the reaction
yield (Table 1, entries 3 vs 4–6). Among the different
indium salts tested, it seems to have no influence, since
the product was obtained only with a slight decrease in
the reaction yield (Table 1, compare entries 3, 7, and
8). However, a significant decrease was observed when
InCl3Æ4H2O was used (Table 1, entry 9).
corresponding selenides in excellent yields (Table 2, en-
tries 5 and 6).
It is well known that diaryl diselenides are more reactive
than aliphatic ones, and much more easily cleaved. In
this way we extended this method to prepare unsymmet-
rical diorganyl selenides starting from aliphatic disele-
nides (Table 2, entries 8–12). Applying the same
methodology and using dibutyl diselenide as the source
for the selenolate anion, the coupling reaction with reac-
tive organic bromides furnishes the desired product in
satisfactory yields (Table 2, entries 7 and 8). However,
in this case, a longer reaction time was required. Increas-
ing the catalyst loading from 2.5 mol % to 10 mol %,
gave a significative improvement on the reaction, afford-
ing the unsymmetrical diorganyl selenide in an excellent
yield (98%) and with a shorter reaction time (Table 2,
entry 9). Also, when the coupling reaction of dibenzil
diselenide with organic bromides was carried out, the
desired product was obtained in good yields using
10 mol % of InBr3 as the catalyst.
Notably, the indium selenolate generated with these
bimetallic system (Zn/In(III)) promotes a cleaner and
faster reaction than those where the selenolate anion is
generated by classic methods. It is worth to mention that
these catalytic methods are considered more applicable
for preparation of functional unsymmetrical diorganyl
selenides because many functional groups cannot with-
stand the harsh conditions for chemical cleavage of
Se–Se bonds.
It is well established that zinc metal rapidly inserts into a
diselenide bond, and the formed complex (RSe)2Zn in
the presence of a Lewis acids such as AlCl3 or RuCl3
and bromide form the unsymmetrical diorganyl sele-
nide.15 For the indium(III) catalyzed cleavage of disele-
nides, a mechanism is proposed as shown in Scheme 2. It
starts with the production of di(organylselenyl)zinc
1, via the insertion of zinc into Se–Se bond. The
indium(III) catalyst reacts with 1 to afford the active
indium(III) species 2, which reacts, subsequently, with
the organic halide R0X, yielding the unsymmetrical dior-
ganyl selenides 3 and species 4. Moreover, further cou-
pling reaction of 4 with R0X affords 3 and regenerates
the catalytic species InX3. As a consequence, this process
enables the consumption of two RSe groups in (RSe)2.
The mild reaction conditions, its speed and the excellent
yields obtained encouraged us to examine the scope and
generality of the present method. Various organic
halides and different diselenides were then examined
for the coupling reaction with the bimetallic system
and the results are summarized in Table 2.
In this second set of experiments, various organic
halides underwent coupling reaction with diphenyl disel-
enides in good yileds (Table 2, entries 1–6). As we can
see in Table 2, 1-bromobutane and 1-iodobutane effi-
ciently undergo this type of selenilation furnishing the
product in 85% and 90%, respectively (Table 2, entries
1 vs 2). Remarkable result was obtained with the unre-
active 1-chlorobutane, which furnishes the desired
unsymmetrical diorganyl selenide in 83% yield (Table
2, entry 3). Different organic bromides were also used.
Allyl and benzyl bromides were converted into their
In summary, the present procedure using the bimetallic
system (Zn/In(III)) provides a practical straightforward
and concise route to a wide range of unsymmetrical
diorganyl selenides. These results are similar or even
superior, in some cases, to those obtained by using
(Zn/Al (III))15a or (Zn/Ru (III))15b as a bimetallic sys-
tem. Compared with these others methodologies, the
indium(III) catalyzed procedure offers significant

A. L. Braga et al. / Tetrahedron Letters 47 (2006) 7195–7198
7197
Table 2. Catalytic cleavage of diorganyl diselenides to unsymmetrical diorganyl selenides
Zn/ InBr3
RSeSeR
+
R'Br
R' SeR
DMF, 100 °C
Time (h)
Entry
R
Halide
InBr3 (mol %)
Yielda (%)
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Bu
Bu
CH3CH2CH2CH2Br
CH3CH2CH2CH2I
CH3CH2CH2CH2Cl
CH3(CH2)3CH2Br
CH2=CHCH2Br
PhCH2Br
1
1
1
1
1
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
10
85
90
83
96
82
93
58
67
98
22
58
57
1
PhCH2Br
48
48
22
72
48
22
CH3(CH2)10CH2Br
CH3(CH2)10CH2Br
PhCH2Br
PhCH2Br
CH3(CH2)10CH2Br
Bu
10
11
12
PhCH2
PhCH2
PhCH2
2.5
10
10
a Yields refer to those of pure isolated products characterized by spectroscopic methods.
Acknowledgments
RSeSeR + Zn
The authors gratefully acknowledge CAPES, CNPq,
FAPERGS and DAAD for financial support. M.W.P.
also acknowledges DAAD for travel grants as part of
a PROBRAL-project.
RSeR'
[RSeZnSeR]
3
1
InX3
ZnX2
R'X
References and notes
RSeInX2
4
(RSe)2InX
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