Use of indium hydride (Cl2InH) for chemoselective reduction of the carbon-carbon double bond in conjugated alkenes

Article abstract of DOI:10.1016/S0040-4039(02)01668-4

Indium hydride (Cl₂InH) generated in situ from a combination of a catalytic amount of indium(III) chloride and sodium borohydride selectively reduces the carbon-carbon double bond in conjugated alkenes such as α,α-dicyano olefins, α,β-unsaturated nitriles, cyano esters, cyanophosphonate, diesters and ketones.

Full text of DOI:10.1016/S0040-4039(02)01668-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7405–7407
Use of indium hydride (Cl InH) for chemoselective reduction of
2
the carbonꢀcarbon double bond in conjugated alkenes
Brindaban C. Ranu* and Sampak Samanta
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
Received 2 July 2002; revised 2 August 2002; accepted 9 August 2002
Abstract—Indium hydride (Cl InH) generated in situ from a combination of a catalytic amount of indium(III) chloride and
2
sodium borohydride selectively reduces the carbonꢀcarbon double bond in conjugated alkenes such as a,a-dicyano olefins,
a,b-unsaturated nitriles, cyano esters, cyanophosphonate, diesters and ketones. © 2002 Elsevier Science Ltd. All rights reserved.
The use of indium metal in organic synthesis has
received considerable attention in recent times because
of its great potential in a variety of organic transforma-
amount (10–15 mol%) of indium(III) chloride and
sodium borohydride in acetonitrile at room tempera-
ture for the period of time required to complete the
reduction (TLC). The usual work-up and purification
produced the corresponding reduction product.
1
tions. One of the latest developments in indium-medi-
2
ated reactions is selective reductions. These reactions
are speculated to go through single electron transfer
(
SET) process. Although metallic indium has been suc-
cessfully used for the reduction of various functionali-
2b
Several structurally diverse conjugated alkenes undergo
selective reduction of their carbonꢀcarbon double bond
using this procedure to provide the corresponding satu-
rated products. The alkenes include a,a-dicyano olefins,
a,b-unsaturated nitriles, cyanoesters, a cyanophospho-
nate, dicarboxylic esters and b-aryl aromatic ketones.
The results are summarized in Table 1. As is evident
from the results, the conjugated monoester (entry 17)
remains inert, whereas the diester (entry 16) is reduced
easily. Apparently, this reagent system, InCl –NaBH is
2
a
ties such as aromatic nitro groups, quinolines,
azides, vic-aryl dibromides, terminal alkynes and
conjugated olefins, among others, two major draw-
backs of these processes are the use of a stoichiometric
amount or more of the costly indium and its limited
applicability to specific types of substrate. Recently,
2
c
2d
2e
2f
2
indium hydride (Cl InH) generated in situ from the
2
combination of sodium borohydride and a catalytic
amount of indium trichloride has been demonstrated to
be a benign alternative to tributyltin hydride in the
dehalogenation of alkyl halides and radical cycliza-
tions. As a part of our interest in indium-mediated
reductions,
applications for this simple reagent and we have discov-
ered that the system InCl –NaBH shows much
improved activity towards reduction of carbonꢀcarbon
double bonds in conjugated alkenes compared to metal-
3
4
quite different from metallic indium in its course of
reduction as conjugated cyanoesters, diesters, nitriles
which are reduced readily by this procedure do not
3
2f
2
d–f
undergo reduction by indium metal. More signifi-
cantly, the reduction of chalcone which was found to be
we initiated an investigation to find
2f,g
problematic using indium metal was successful using
this reagent system (entry 18). In addition, reductions
using this procedure are faster and proceed at room
temperature unlike using indium metal, which requires
3
4
2
f
lic indium and our results are presented here (Scheme
).
2f
a temperature of 90°C for a longer period. To ascer-
tain the role of indium(III) chloride a few reactions
were carried out with the conjugated nitrile (listed in
entry 7), cyanoester (entry 10), dicyano-olefin (entry 1)
1
4
The experimental procedure is very simple. The conju-
gated alkene was stirred with a solution of a catalytic
Keywords: indium chloride; sodium borohydride; reduction; conju-
gated alkene; CꢁC bond.
*
Corresponding author. Fax: 91-33-4732805; e-mail: ocbcr@
mahendra.iacs.res.in
Scheme 1.
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01668-4

7
406
B. C. Ranu, S. Samanta / Tetrahedron Letters 43 (2002) 7405–7407
Table 1. The reduction of CꢁC bond in conjugated alkenes by InCl /NaBH4
3
Entry
Alkene
E1
Time (h)
Yield (%)a
R1
Ph
R2
E2
1
2
3
4
5
6
7
8
H
H
Me
Me
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
H
3
3
3.5
4
3.5
4
12
12
85
83
79
79
83
81
69
57
p-(Cl)-C H
Ph
p-(Me)-C H
cy-C H
Me CH
Ph
p-(Me)-C H
6
4
6
4
6
10
Me
H
H
2
H
6
4
9
H
CN
H
5
84
1
1
0
1
Ph
Ph
H
Me
CN
CN
CO Et
3
4.5
88
2
b
CO Et
82 (55:45)
78
2
1
2
H
CN
CO Et
5
2
13
14
15
16
17
18
Me CH
Me
CN
CN
CN
CO Et
5
4.5
4.5
6
18
0.5
85 (60:40)b
84
81
87
No reaction
96
2
2
cy-C H
CO Et
6
10
14
2
cy-C H
CO Et
8
2
Ph
Ph
Ph
H
H
H
CO Et
CO Et
2
2
CO Et
H
COPh
2
H
1
9
H
H
COPh
0.75
88
a
Yields refer to those of pure isolated products characterized by spectral data (IR, 1H, 13C NMR).
The figure in parenthesis denotes the diastereomeric ratio of the product.
b
2f
and chalcone (entry 18) under identical reaction condi-
tions without the indium(III) chloride, and no reduc-
tion was observed in each case. Thus, it may be
metal which was reported earlier and leaves great
promise for other application of the indium hydride.
assumed that the reductions are effected by Cl InH,
2
generated in situ from NaBH and InCl through a
radical process.
4
3
Acknowledgements
3
In general, reductions using this procedure are clean,
high-yielding and quite fast. The reaction conditions
are mild enough (room temperature) to tolerate a sensi-
tive furan ring (entry 12). This reagent system is also
highly chemoselective reducing only the CꢁC bond
without any effect on other reducible functionality.
We are pleased to acknowledge financial support from
the CSIR, New Delhi [Grant No. 01(1739)/02] for this
investigation. S.S. is also thankful to CSIR for his
fellowship.
References
In conclusion, the indium hydride, Cl InH generated in
2
situ from a combination of sodium borohydride and a
catalytic amount of indium(III) chloride provides a
highly chemoselective reduction of the carbonꢀcarbon
double bonds in a wide range of activated conjugated
alkenes. Certainly, this reagent offers significant
improvements with regard to convenience, cost, mild-
ness and efficiency over the similar reduction by indium
1
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B. C. Ranu, S. Samanta / Tetrahedron Letters 43 (2002) 7405–7407
7407
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To a stirred solution of anhydrous indium(III) chloride (30
mg, 0.135 mmol, Aldrich) and sodium borohydride (56
mg, 1.5 mmol, Aldrich) in dry acetonitrile (3 mL) was
added a solution of 1,1-dicyano-2-phenyl ethylene (154
mg, 1 mmol) in acetonitrile (1 mL) at room temperature
(28–30°C) under nitrogen. The reaction mixture was
stirred for another 3 h as monitored by TLC and
quenched with water (0.5 mL). The reaction mixture was
extracted with ether (3×10 mL) and ether extract was
4
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Pitts, M. R.; Harrison, J. R.; Moody, C. J. J. Chem. Soc.,
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2
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2 4
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. General experimental procedure. Representative one for
the reduction of 1,1-dicyano-2-phenyl ethylene (entry 1).
leave the crude product which was purified by column
chromatography over silica gel (hexane–ether, 70:30) to
provide the corresponding alkane (131 mg, 85%) as a
white solid, mp 87–88°C whose spectral data are in good
3
4
2f
agreement with those reported earlier.