Indium as a reducing agent. Chemoselective reduction of α-halocarbonyl compounds and benzyl halides by indium metal in water under sonication

Article abstract of DOI:10.1039/a901493d

Indium metal in water reduces a-halocarbonyl compounds and benzyl iodides to the corresponding dehalogenated products in excellent yields under sonication although simple alkyl and aryl iodides remained inert under these conditions.

Full text of DOI:10.1039/a901493d

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Indium as a reducing agent. Chemoselective reduction
of á-halocarbonyl compounds and benzyl halides by indium
metal in water under sonication
Brindaban C. Ranu,* Pinak Dutta and Arunkanti Sarkar
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur,
Calcutta - 700 032, India
Received (in Cambridge) 23rd February 1999, Accepted 8th March 1999
Table 1 Reduction of α-halocarbonyl compounds and benzyl halides
by In/H2O
Indium metal in water reduces á-halocarbonyl compounds
and benzyl iodides to the corresponding dehalogenated
products in excellent yields under sonication although
simple alkyl and aryl iodides remained inert under these
conditions.
Yield
(%)a
Entry
Substrate
t/h
Product
1
2
3
4
5
6
PhCOCH2I
PhCOCH2Br
PhCOCH(CH3)I
PhCOCH(C2H5)I
PhCOCH(C2H5)Br
BrCH2CO2CH2CH3
3
8
3
3.5
7.5
6.5
PhCOCH3
PhCOCH3
PhCOCH2CH3
PhCOCH2C2H5
PhCOCH2C2H5
CH3CO2CH2CH3
90
86
87
91
85
78
In recent times, indium has emerged as one of the metals of
growing interest because of its great synthetic potential.1
However, although indium has been used extensively in
carbonyl addition reactions,2 its use in other domains has not
been explored to a great extent.3 Remarkably, the first ioniz-
ation potential of indium (5.8 eV) is much lower than that of
zinc (9.4 eV) or tin (7.3 eV), and even magnesium (7.6 eV)
and thus indium metal should participate readily in SET
(single electron transfer) processes and therefore be a potential
reducing agent. Surprisingly, reduction by indium metal is still
unexplored except for a couple of recent examples.4 During a
recent investigation into the coupling of alkyl and aryl halides
by indium in dry DMF we observed a competing reduction
process in the case of α-iodoketones.5 This prompted us to
initiate a systematic investigation into the reduction by indium
metal and we have discovered that indium in water reduces
α-halocarbonyl compounds very efficiently (Scheme 1).
7
2.5
89
8
9
8
83
88
i
3.5
RCOCH2X
RCOCH3
X = I, Br
Scheme 1 Reagents and conditions: (i) In, H2O, ultrasound.
10
4.5
6
85
75
In a typical experimental procedure, a mixture of α-halo-
carbonyl compound and indium metal in water was sonicated
in an ultrasonic cleaner for a certain period of time as required
to complete the reaction. Usual workup and purification pro-
duced the corresponding dehalogenated carbonyl compound.
Stirring at room temperature did not initiate the reaction even
after 24 h. However, the reduction proceeded at reflux, although
the reaction is rather slow and messy compared to that under
sonication.
A wide range of structurally different α-iodo- and bromo-
ketones and esters underwent reduction by this procedure to
provide the corresponding dehalogenated carbonyl compounds.
The results are reported in Table 1. The reduction of bromo
compounds is slow compared to that of iodo compounds.
Although alkyl- and aryl-substituted iodides (entry 12, 13)
remained inert under these conditions, benzyl iodides (entry 14,
15) were reduced. Also selective reduction of a side chain-
substituted iodo functionality is achieved in the presence of
iodo-substitution on the aromatic ring (entry 16). The reactions
are, in general, reasonably fast and high-yielding. One very
important aspect of this procedure is the use of water as
reaction medium which has attracted considerable interest
in recent times in the context of green chemistry.6 It may
be assumed that these reductions are also going through a
11
12
19
24
5
13
14
85
86
5
15
16
11
85
a Yields refer to pure isolated products fully characterised by spectral
data.
SET process like other metal-mediated reactions in aqueous
media.
In conclusion, this procedure provides a very efficient
and general methodology for chemoselective reduction of
J. Chem. Soc., Perkin Trans. 1, 1999, 1139–1140
1139

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α-halocarbonyl and benzyl halides and broadens the scope of
indium-mediated reductions.
References
1 P. Cintas, Synlett, 1995, 1087.
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Lett., 1997, 38, 869; M. B. Isaac and L. A. Paquette, J. Org. Chem.,
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Experimental
α-Halocarbonyl compounds have been prepared by standard
procedures.7 Indium metal was purchased from SRL, India,
and was used without any treatment.
General procedure for reduction
3 S. Araki, A. Imai, K. Shimizu, M. Yamada, A. Mori and
Y. Butsugan, J. Org. Chem., 1995, 60, 1841; B. C. Ranu and A. Majee,
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K. Subburaj, T. Hirashita, K. Shibutani, H. Yamamura, M. Kawai
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6 C.-J. Li and T.-H. Chan, Organic Reactions in Aqueous Media, John
Wiley and Sons, New York, 1997.
A mixture of α-halocarbonyl compound or benzyl halide
(1 mmol) and indium metal (1 mmol, cut into small pieces)
in water (2 cm3) was sonicated in an ultrasonic cleaner for
a certain period of time as required to complete the reaction
(monitored by TLC). The reaction mixture was extracted with
ether and the ether extract was washed with brine and dried
(Na2SO4). Evaporation of solvent followed by purification by
silica gel column chromatography produced the corresponding
dehalogenated compound. Identification of the products was
made on the basis of IR and 1H NMR evidence in comparison
with authentic samples.
7 S. Motohashi and M. Satomi, Synthesis, 1982, 1021; P. Dowd and
S. C. Choi, Tetrahedron, 1989, 45, 77.
Acknowledgements
We gratefully acknowledge the financial support from CSIR,
New Delhi [Grant No. 01(1504)/98] for this investigation. P. D.
also thanks CSIR for his fellowship.
Communication 9/01493D
1140
J. Chem. Soc., Perkin Trans. 1, 1999, 1139–1140