Dichloroindium hydride (Cl2InH): A convenient reagent for stereoselective reduction of vic-dibromides to (E)-alkenes

Article abstract of DOI:10.1055/s-2003-39165

Dichloroindium hydride (Cl₂InH) generated in situ from the combination of a catalytic amount of indium(III) chloride and sodium borohydride in acetonitrile reduces activated vic-dibromides to the corresponding (E)-alkenes in excellent yields.

Full text of DOI:10.1055/s-2003-39165

1012
SHORT PAPER
Dichloroindium Hydride (Cl2InH): A Convenient Reagent for Stereoselective
Reduction of vic-Dibromides to (E)-Alkenes
Stereoselective
R
r
eduction
i
of vic
-
D
ibromides
d
to
(
E
)-Alken
a
e
s
ban C. Ranu,* Arijit Das, Alakananda Hajra
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta - 700 032, India.
Fax 91(33)24732805; E-mail: ocbcr@iacs.res.in
Received 6 December 2002; revised 24 February 2003
and a catalytic amount of indium(III) chloride (20 mol%
Abstract: Dichloroindium hydride (Cl2InH) generated in situ from
of dibromide) in anhydrous acetonitrile at –10 °C for
2.75–5 hours as required to complete the reaction (TLC).
the combination of a catalytic amount of indium(III) chloride and
sodium borohydride in acetonitrile reduces activated vic-dibro-
The reaction mixture was then quenched with a few drops
of water and extracted with diethyl ether. Evaporation of
diethyl ether followed by column chromatography of the
crude product furnished the pure alkene.
mides to the corresponding (E)-alkenes in excellent yieids.
Key words: reductions, (E)-alkenes, vic-dibromides, indium(III)
chloride, sodium borohydride
Several structurally diverse vic-dibromides substituted
with an electron-withdrawing group such as CO2R, CN
underwent clean reductive debrominations by this proce-
dure to provide the corresponding alkenes. The results are
summarized in Table 1. Very interestingly, only the (E)-
alkenes are obtained from both erythro(meso) or threo(dl)
dibromides. Thus, a (Z)-alkene, diethyl maleate, is easily
converted to the (E)-isomer diethyl fumarate, through its
dibromide (entries 13,14). Aryl- as well as alkyl-substitut-
ed dibromides undergo reductive debrominations with
this reagent. This procedure is also effective for the reduc-
tion of vic-dibromoalkene to the corresponding alkyne
(entry 15).
Indium metal has been the subject of continued interest
due to its great potential in organic synthesis1 because of
its close resemblance with magnesium, zinc, and tin in
several respects including first ionization potential and its
use for selective reduction of various functional groups.2
However, two major drawbacks of these indium-mediated
reductions are the use of a stoichiometric amount or more
of the costly indium reagent and its limited applicability to
specific types of substrate.2 As these reactions are specu-
lated to proceed through a radical process, search for other
indium derivatives as better radical agents led to the dis-
covery of a couple of indium hydrides.3 Dichloroindium
hydride (Cl2InH) generated in situ from the reaction of so-
dium borohydride and a catalytic amount of indium(III)
chloride has been demonstrated to be a benign alternative
to tributyltin hydride in the dehalogenation of alkyl
halides3a and other radical cyclizations.3b Recently we
have reported4 a very successful use of this reagent for the
reduction of the carbon-carbon double bond in conjugated
alkenes and wish to disclose here another application of
this reagent for the reduction of activated vic-dibromides
to (E)-alkenes (Scheme 1).
Presumably, the reductions are going through a radical
process effected by Cl2InH, a radical agent3a,b formed in
situ by the reaction of NaBH4 and InCl3. It was observed
that sodium borohydride alone failed to initiate any reac-
tion. It is therefore suggested that the reaction occurs via
a common, relatively stable radical intermediate, which
directly collapses to the (E)-alkene. Apparently, this re-
agent, Cl2InH is quite different and more effective than
metalic indium in the reduction of vic-dibromides, as non-
aromatic substrates which are debrominated readily by
this procedure do not undergo reduction by indium met-
al.2d Moreover, in acetonitrile debromination by indium
metal does not proceed at all,2d whereas acetonitrile is the
solvent of choice in the present procedure.
In general, debrominations by this procedure are clean,
high yielding and reasonably fast. The reaction conditions
are mild enough (–10 °C) compared to that by indium
metal (reflux in MeOH) and the reductions occur in the
presence of sensitive moieties such as the furan ring (entry
9) and methylenedioxy group (entry 7). However, for an
effective reductive debromination this procedure requires
the presence of an activating moiety in dibromides possi-
bly for the stabilization of the radical intermediate formed
after cleavage of the C–Br bond. Thus, the absence of
such an activating group leads to debromination (entry 16)
as observed earlier.3a It has been found that with the use of
20 mol% of indium(III) chloride at –10 °C the reactions
Scheme 1
The experimental procedure is very simple. The vic-dibro-
mide was stirred with a solution of sodium borohydride
Synthesis 2003, No. 7, Print: 20 05 2003.
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© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

SHORT PAPER
Stereoselective Reduction of vic-Dibromides to (E)-Alkenes
1013
Table 1 Debromination of vic-Dibromides by Cl2InH
and certainly shows great potential for further useful ap-
plications.
Entry
R
R1
Stereoiso-Time Yield Ref.
mer
meso
dl
(h)
(%)a
NMR spectra were recorded on a Bruker DPX 300 instrument at
300 MHz for 1H and at 75 MHz for 13C NMR. IR spectra were mea-
sured on a FT 8300 Shimadzu spectrometer. Melting points are de-
termined on a glass disk with an electrical bath (Reichert, Austria)
and are uncorrected. Acetonitrile was dried over P2O5 and distilled
before use. NaBH4 and InCl3 was purchased from Aldrich.
5
1
2
3
4
5
6
7
Ph
Ph
Ph
Ph
Ph
Ph
2.75 85
3.00 80
2.75 82
5
5
CO2Me threo
5
CO2Me erythro 3.25 80
Debromination of meso-Dibromostilbene to trans-Stilbene;
General Procedure (entry 1)
2d
7
3-(MeO)-C6H4 CO2Et
4-(MeO)-C6H4 CO2Et
CO2Et
erythro 3.00 85
erythro 3.00 81
erythro 3.25 82
The dibromide (340 mg, 1 mmol) was added to a stirred solution of
NaBH4 (59 mg, 1.5 mmol) and InCl3 (98%, Aldrich, 45 mg, 0.2
mmol, 20 mol% of dibromide) in anhyd CH3CN (2 mL) at –10 °C
and stirring was continued at that temperature for 2.75 h as indicated
by TLC. The reaction mixture was then quenched with a few drops
of H2O and extracted with Et2O (3 × 15 mL). Evaporation of Et2O
followed by column chromatography of the crude product over sil-
ica gel (hexane–Et2O, 95:5) furnished the pure trans-stilbene as a
colorless solid (153 mg, 85%); mp 122–23 °C (lit.5 mp 122–24 °C)
whose 1H NMR spectra is also in good agreement with that report-
ed.5
8
8
9
CO2Et
erythro 3.75 80
CO2Me erythro 3.50 78
This procedure is followed for the reduction of all the dibromides
listed in Table 1. All of the products obtained except those in entries
7 and 9 are known compounds and are easily identified by compar-
ison of their IR and NMR (1H and 13C) spectra with those report-
ed.2d,5,6,7,8,9 The spectral (IR, 1H and 13C NMR) data and elemental
analyses of the compounds (entries 7,9) which are not readily found
are provided here.
5
6
10
11
Ph
CN
CN
erythro 3.50 78
erythro 3.25 80
5
5
5
5
12
13
14
15
Me
CO2Me erythro 3.00 78
EtO2C
EtO2C
CO2Et
CO2Et
meso
dl
2.75 80
3.00 84
3.25 79
trans-1-Carboxyethyl-2-(3′,4′-methylenedioxyphenyl)ethene
(entry 7)
White crystals; mp 51–53 °C; Rf 0.67.
IR (KBr): 1722, 1620 cm–1.
1H NMR (CDCl3): δ = 7.99 (d, J = 15.8 Hz, 1 H), 7.04 (m, 2 H), 6.24
(d, J = 15.8 Hz, 1 H), 6.01 (s, 2 H), 5.92 (s, 1 H), 4.22 (q, J = 7.1 Hz,
2 H), 1.30 (t, J = 7.1 Hz, 3 H).
9
16
meso
5.00 85
13C NMR (CDCl3): δ = 167.5, 149.9, 148.7, 144.6, 129.2, 124.7,
116.6, 108.9, 106.8, 101.9, 60.7, 14.7.
a Yields refer to those of pure isolated products characterized by spec-
tral data (IR, 1H and 13C NMR).
Anal. Calcd for C12H12O4: C, 65.44; H, 5.49. Found: C, 65.32; H,
5.43.
are clean producing only the corresponding (E)-alkenes.
The use of a lower amount of indium(III) chloride (5–10
mol%) resulted in incomplete conversion even after a pe-
riod of 10–12 h, while the operations at higher tempera-
ture (0–25 °C) led to a mixture of alkenes and saturated
compounds.
trans-1-Carboxymethyl-2-(2′-furyl)ethene (entry 9)
Pale yellow liquid; Rf 0.70.
IR (neat): 1724, 1610 cm-1.
1H NMR (CDCl3): δ = 7.60 (d, J = 1.4 Hz, 1 H), 7.63 (d, J = 15.8
Hz, 1 H), 6.73 (d, J = 3.4 Hz, 1 H), 6.58 (m, 1 H), 6.43 (d, J = 15.8
Hz, 1 H), 3.90 (s, 3 H).
13C NMR (CDCl3): δ = 167.8, 151.2, 145.1, 131.5, 115.7, 115.1,
112.6, 51.9.
In summary, the present procedure using Cl2InH generat-
ed in situ from the combination of sodium borohydride
and a catalytic amount of indium(III) chloride provides an
efficient and general methodology for reductive debromi-
nation of vic-dibromides to the corresponding (E)-al-
kenes. The significant advantages offered by this method
are: (a) no over-reduction of double or triple bonds, (b)
tolerance to sensitive moieties, (c) exclusive formation of
(E)-alkenes and thus an easy conversion of a cis to a trans
olefin. This reagent also provides much improvement
with regard to convenience, cost, mildness, and efficiency
over similar reductions by indium metal reported earlier2d
Anal. Calcd for C8H8O3: C, 63.19; H, 5.30. Found: C, 63.25; H,
5.22.
Acknowledgments
We are grateful to CSIR, New Delhi who provided financial support
[Grant No. 01(1739)/02]. A.D. and A.H. are also thankful to CSIR
for their fellowships.
Synthesis 2003, No. 7, 1012–1014 ISSN 0039-7881 © Thieme Stuttgart · New York

1014
B. C. Ranu et al.
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