An indium-TMSCl promoted reaction of diphenyl diselenides and aldehydes: novel routes to selenoacetals and alkyl phenyl selenides

Article abstract of DOI:10.1016/j.tetlet.2006.06.012

The reaction of diphenyl diselenides with aldehydes in the presence of In-TMSCl has been investigated. Aliphatic aldehydes provide the corresponding selenoacetals, whereas aromatic aldehydes lead predominantly to alkyl phenyl selenides under the same reac

Full text of DOI:10.1016/j.tetlet.2006.06.012

Tetrahedron Letters 47 (2006) 5677–5680
An indium–TMSCl promoted reaction
of diphenyl diselenides and aldehydes: novel routes
to selenoacetals and alkyl phenyl selenides
Brindaban C. Ranu* and Tanmay Mandal
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India
Received 29 April 2006; revised 22 May 2006; accepted 2 June 2006
Available online 21 June 2006
Abstract—The reaction of diphenyl diselenides with aldehydes in the presence of In–TMSCl has been investigated. Aliphatic
aldehydes provide the corresponding selenoacetals, whereas aromatic aldehydes lead predominantly to alkyl phenyl selenides under
the same reaction conditions. This constitutes a new approach for the synthesis of selenoacetals and selenides from aldehydes.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Indium metal and its derivatives have been found to
have great potential for a variety of organic transforma-
tions and have generated new interesting chemistry.1 As
a part of our program to develop new synthetic proce-
dures using indium reagents,1e,2 we have investigated
In–TMSCl2o and discovered a very interesting reaction
of diphenyl diselenides with aldehydes promoted by this
reagent. Aliphatic aldehydes when heated under reflux
with diphenyl diselenides in the presence of In–TMSCl
in acetonitrile produced the corresponding selenoacetals
whereas from aromatic aldehydes, alkyl phenyl selenides
under the same reaction conditions were produced
(Scheme 1).
and mildly acidic conditions, inert to Grignard reagents
and thus have similar properties to their oxygen and sul-
fur analogues. They are also useful for carbonyl protec-
tion.3 Usually, selenoacetals are prepared from the
corresponding carbonyl compounds by reaction with
selenols or [B(SeMe)3] under the catalysis of protic or
Lewis acids.4 Alternatively, they can be prepared by
exchange reactions between O-acetals and tris(phenyl-
seleno)borane.5 However, all these reagents—selenols
and tris(alkylseleno)borane—are usually prepared from
dialkyl diselenides.4 Thus, a method involving dialkyl
diselenides directly would be more convenient and
practical.
Selenoacetals are versatile intermediates in organic syn-
thesis and have played a crucial role in the development
of organoselenium chemistry.3 They are stable in basic
Organic selenides are of considerable interest in acade-
mia as well as in industry because of their wide involve-
ment in organic synthesis6a and their biological
activities.6b Although a number of procedures for the
synthesis of dialkyl/alkyl aryl selenides have been
reported,7 most use alkyl halides as starting materials.
To the best of our knowledge, no method is available
starting from aldehydes. Thus, the present protocol
(Scheme 1) provides new routes for the synthesis of sele-
noacetals and alkyl phenyl selenides.
R = alkyl
RCH(SePh)2
PhSeSePh
In, TMSCl
CH3CN, reflux
RCHO
RCH(SePh)2
R = aryl
+
RCH2SePh
The experimental procedure is very simple.8 A solution
of diphenyl diselenide, an aldehyde and trimethylsilyl
chloride in acetonitrile is heated under reflux in the pres-
ence of indium metal for a period of time (Table 1), stan-
dard work-up and extraction with ether providing the
product.
Scheme 1.
Keywords: Selenoacetal; Selenides; Indium; Trimethylsilyl chloride;
Aldehydes.
*
Corresponding author. Tel.: +91 33 24734971; fax: +91 33
24732805; e-mail: ocbcr@iacs.res.in
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.06.012

5678
B. C. Ranu, T. Mandal / Tetrahedron Letters 47 (2006) 5677–5680
Table 1. Synthesis of selenoacetals and aryl phenyl selenides
Entry
1
Aldehyde
Time (h)
2.0
Product
Yielda (%)
70
Ref.
( )
( )
2 CH(SePh)2
2 CHO
( )
6 CH(SePh)2
( )
2
3
2.5
2.5
78
72
6 CHO
( )
8 CH(SePh)2
( )
8 CHO
( )
12CH(SePh)2
( )
4
5
6
7
2.5
4.5
2.0
2.0
76
75
71
80
12CHO
( )
( )
Ph 2 CH(SePh)2
Ph 2 CHO
CHO
CH(SePh)2
CH(SePh)2
CHO
8
9
7.0
5.5
75
76
2j
CHO
CH2SePh
CH2SePh
CHO
MeS
MeS
CHO
CH2SePh
10
3.5
72
AllylO
AllylO
OMe
OMe
CHO
CH2SePh
11
12
13
2.5
2.5
3.0
65
75
73
Me2N
AcO
Me2N
CH2SePh
CHO
AcO
CHO
CH2SePh
OMe
OMe
CHO
CH2SePh
14
15
3.5
3.5
72
74
OMe
MeO
OMe
CH2SePh
CHO
MeO
CH2SePh
CHO
O
+
O
16
4.0
80
2j
CH(SePh)2
O
O
(86:14)
O
O

B. C. Ranu, T. Mandal / Tetrahedron Letters 47 (2006) 5677–5680
5679
Table 1 (continued)
Entry
Aldehyde
CHO
Time (h)
7.0
Product
CH2SePh
Yielda (%)
Ref.
17
70
+
Br
Br
Br
CH(SePh)2
(88:12)
CH2SePh
CHO
+
Cl
Cl
18
6.5
75
2j
CH(SePh)2
Cl
(85:15)
a Yields refer to those of pure and isolated products characterized by IR, 1H and 13C NMR spectroscopic data and elemental analysis.
A wide range of structurally diverse aliphatic and aro-
matic aldehydes underwent reactions with diphenyl
diselenides using this procedure to produce the corre-
sponding products. The results are summarized in Table
1. All the aliphatic aldehydes produced the correspond-
ing selenoacetals (entries 1–7), whereas aromatic
aldehydes furnished exclusively (entries 8–15) or
predominantly (entries 16–18) the corresponding aryl
phenyl selenides. In the reactions of aromatic aldehydes
where a mixture of aryl phenyl selenides and selenoace-
tals was produced, the proportion of selenides was in-
creased at the cost of selenoacetals after longer periods
although 100% conversion was not achieved. However,
an isolated pure selenoacetal of 3-bromobenzaldehyde
was converted to the corresponding selenide under the
same reaction conditions after 6 h. When the reactions
of aliphatic aldehydes were allowed to proceed for long-
er periods, no alkyl selenides were obtained. Thus, it
seems that the reactions of aliphatic aldehydes stopped
at the selenoacetal stage, whereas the reactions of aro-
matic aldehydes proceeded further to produce selenides.
The exact reason for this difference of reactivity is not
clear. We found that a radical quencher considerably
affects the course of the reaction of aromatic aldehydes.
ished, a 1:1 mixture of selenoacetal and selenide being
obtained whereas in the normal reaction the selenide
was obtained as the only isolable product after 3 h. In
contrast, the quencher had no effect on the conversion
of an aliphatic aldehyde (decanal, entry 3) to the sele-
noacetal. Thus, we speculate that a free radical is
involved in the formation of aryl phenyl selenides. Based
on these observations, we propose the reaction course
shown in Scheme 2. As indium metal is well known to
initiate radical processes,1e it may be that the initially
formed selenoacetal II undergoes radical cleavage fol-
lowed by anion formation leading to selenides III in
reactions of aromatic aldehydes.
In general, the reactions were very clean, fast and high
yielding. The products were obtained in high purity.
Although a few aromatic aldehydes (entries 16–18) led
to mixtures of selenides and selenoacetals, these could
be separated by careful column chromatography. Vari-
ous functional groups such as OAc, OMe, SMe, O-allyl,
NMe2, Cl and Br survived under the reaction conditions
intact. The reactions did not proceed at all either in the
absence of TMSCl or in the absence of In metal, that is,
the combined In–TMSCl reagent is essential for this
reaction. Replacement of TMSCl with BF3 did not give
the products. Indium(I) iodide which is very efficient for
the cleavage of diphenyl diselenides2j,k,p was also in-
effective. Acetonitrile was found to be the best solvent,
whereas in methylene chloride the reaction was very
slow, and in THF poor yields of the product were
obtained. Finally, ketones remained completely inert
under these experimental conditions.
Thus, when the reaction of 2-methoxybenzaldehyde
(entry 13) was carried out in the presence of a quencher,
4-hydroxy TEMPO under reflux for 5 h, the formation
of the corresponding selenide was considerably dimin-
2TMSCl
In
RCHO
TMSCl
PhSeSePh
PhSeSiMe3
In conclusion, the present procedure8 using In–TMSCl
provides a new route for the synthesis of selenoacetals
and aryl phenyl selenides from aldehydes. The significant
features of this procedure are (a) simple one-pot opera-
tion, (b) use of stable and readily available diphenyl
diselenide, (c) rapid reaction and (d) high isolated yields
of products. Thus, it provides a better and practical alter-
native to the existing procedures4,5,7 and we believe that
it will find useful applications in organic synthesis.
SePh
OSiMe3
SePh
PhSeSiMe3
RCH
RCH
SePh
II
I
In
( )
+
.
( )
(-)
H3O
In
RCHSePh
RCHSePh
RCH2SePh
III
Scheme 2.

5680
B. C. Ranu, T. Mandal / Tetrahedron Letters 47 (2006) 5677–5680
7. (a) Bieber, L. W.; de Sa, A. P. F.; Menezes, P. H.; Goncalves,
Acknowledgements
S. M. C. Tetrahedron Lett. 2001, 42, 4597–4599; (b) Krief,
A.; Derock, M. Tetrahedron Lett. 2002, 43, 3083–3086, and
references cited therein; (c) Nishino, T.; Okada, M.; Kuroki,
T.; Watanabe, T.; Nishiyama, Y.; Sonoda, N. J. Org. Chem.
2002, 67, 8696–8698, and references cited therein; (d) Grieco,
P. A. J. Org. Chem. 1978, 43, 1283–1285.
We are pleased to acknowledge the financial support
from CSIR, New Delhi (Grant No. 01(1936)/04), for this
investigation. T.M. also thanks CSIR for his fellowship.
8. General experimental procedure for the synthesis of seleno-
acetals and aryl phenyl selenides. Representative procedure
for 1,1-diphenylselenooctane (entry 2).
References and notes
To a stirred solution of diphenyl diselenide (1 mmol,
312 mg) and trimethylsilyl chloride (2 mmol, 218 mg) in
dry acetonitrile (3 mL) was added octanal (1 mmol, 128 mg)
and the mixture was stirred for 2 min at room temperature.
The reaction mixture was then heated under reflux with
indium metal (1 mmol, 115 mg, cut into small pieces) for
2.5 h. After completion of the reaction (TLC), acetonitrile
was evaporated in vacuo and the residue was extracted with
ether (3 · 10 mL). The combined ether extract was then
washed with brine, dried (Na2SO4) and evaporated to leave
the crude product which was purified by column chroma-
tography over silica gel (hexane–ether 98:2) to furnish 1,1-
diphenylselenooctane as a yellow liquid (331 mg, 78%); IR
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3019; (e) Ranu, B. C. Eur. J. Org. Chem. 2000, 2347–2356;
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(neat): 1436, 1475, 1578 cmÀ1
;
1H NMR (300 MHz,
CDCl3): d 0.78 (t, J = 6.6 Hz, 3H), 1.13–1.18 (m, 7H),
1.46–1.49 (m, 3H), 1.80–1.89 (m, 2H), 4.40 (t, J = 6.5 Hz,
1H), 7.16–7.22 (m, 6H), 7.48–7.51 (m, 4H); 13C NMR
(CDCl3, 75 MHz): d 13.9, 22.5, 28.2, 28.7, 28.9, 31.6, 36.9,
44.0, 127.8 (2C), 128.9 (4C), 130.3 (2C), 134.5 (4C). Anal.
Calcd for C20H26Se2: C, 56.61; H, 6.18. Found: C, 56.37; H,
6.03.
This procedure was followed for all the aldehydes listed in
Table 1. As mentioned earlier, aliphatic aldehydes pro-
duced the corresponding selenoacetals (entries 1–7) and
aromatic aldehydes provided aryl phenyl selenides (entries
8–15) or mixtures of aryl phenyl selenides and selenoacetals
(entries 16–18). The known compounds (entries 8, 16 and
18) were identified by comparison of their spectral data
with those reported (Table 1), and the new compounds
(entries 1–7, 9–15 and 17) were properly characterized from
1
their IR, H NMR and 13C NMR spectroscopic data and
elemental analysis. The data for two representative com-
pounds are presented below:
1,1-Diphenylselenobutane (entry 1): Yellow liquid; IR
(neat): 1437, 1475, 1578 cmÀ1
;
1H NMR (300 MHz,
CDCl3): d 0.85 (t, J = 7.35 Hz, 3H), 1.51–1.64 (m, 2H),
1.87–1.94 (m, 2H), 4.49 (t, J = 6.60 Hz, 1H), 7.24–7.30 (m,
6H), 7.56–7.59 (m, 4H); 13C NMR (75 MHz, CDCl3): d
13.2, 21.4, 43.7, 47.9, 127.8 (2C), 128.8 (4C), 130.2 (2C),
134.5 (4C). Anal. Calcd for C16H18Se2: C, 52.19; H, 4.93.
Found: C, 51.97; H, 4.88.
4-Methylthiophenylmethyl phenyl selenide (entry 9): Yel-
low solid, mp 55–57 ꢁC; IR (KBr): 1438, 1475, 1577 cmÀ1
;
1H NMR (300 MHz, CDCl3): d 2.44 (s, 3H), 4.06 (s, 2H),
7.08–7.24 (m, 7H), 7.41–7.44 (m, 2H); 13C NMR
(75 MHz, CDCl3): d 15.6, 31.7, 126.6 (2C), 127.2, 128.3,
128.8 (2C), 129.2 (2C), 130.2, 133.5 (2C), 135.4. Anal.
Calcd for C14H14SSe: C, 57.33; H, 4.81. Found: C, 57.25;
H, 4.73.
6. (a) Krief, A.; Hevesi, L. In Organoselenium Chemistry;
Springer-Verlag: Berlin, 1998; Vol. 1; (b) Krief, A. In
Comprehensive Organo-metallic Chemistry; Trost, B. M.,
Ed.; Pergamon Press: Oxford, 1991; pp 85–192.