Stereoselective debromination and selective reduction of vic-dibromides with nickel boride

Article abstract of DOI:10.1139/V06-125

A simple procedure is reported for the stereoselective debromination of vic-dibromides with nickel boride at ambient temperature. Debromination with concomitant reduction of vic-dibromides to give dihydro products in a one-pot reaction is also reported. α,β-Dibromoketones can also be converted to their corresponding alcohols.

Full text of DOI:10.1139/V06-125

1019
Stereoselective debromination and selective
reduction of vic-dibromides with nickel boride
Jitender M. Khurana, Bhaskar M. Kandpal, Gagan Kukreja, and Purnima Sharma
Abstract: A simple procedure is reported for the stereoselective debromination of vic-dibromides with nickel boride at
ambient temperature. Debromination with concomitant reduction of vic-dibromides to give dihydro products in a one-
pot reaction is also reported. α,β-Dibromoketones can also be converted to their corresponding alcohols.
Key words: debromination, vic-dibromides, stereoselective, reduction, E-alkenes.
Résumé : On a mis au point une méthode simple de débromuration stéréosélective de dibromures vicinaux impliquant
l’utilisation du borure de nickel à la température ambiante. On rapporte aussi la réaction monotope de débromuration
avec réduction concomitante des dibromures vicinaux qui conduit à la formation des produits dihydrogénés. On peut
aussi transformer les α,β-dibromocétones en alcools correspondants.
Mots clés : débromuration, dibromures vicinaux, stéréosélective, réduction, E-alcènes.
[Traduit par la Rédaction] Khurana et al. 1023
Introduction
quantitative debromination with nickel boride generated in
situ from nickel chloride and sodium borohydride using a
molar ratio of 1:2:6 (substrate–NiCl2–NaBH4) in THF to
give the corresponding alkenes (eq. [1]). The reactions were
complete in 30–120 min at ambient temperature as moni-
tored by TLC. Chalcone dibromides and other α,β-dibromo-
ketones did not undergo complete debromination under
these conditions. Smooth debromination of different chalcone
dibromides and other α,β-dibromoketones, which were solu-
ble in methanol, was successfully achieved to afford the cor-
responding chalcones or enones (Table 2, runs 17–28) in
quantitative yields using a molar ratio of 1:5:2 (substrate–
NiCl2–NaBH4) in methanol at ambient temperature for 15–
60 min (eq. [1]). The carbonyl, carboxylic, carbmethoxy,
highly sensitive furan and benzopyrone rings remained unaf-
fected under these conditions. Even steroidal derivatives could
be readily debrominated. The debrominations are stereo-
selective as (E)-stilbene was obtained from meso- and dl-
stilbene dibromides, and fumaric acid was obtained from
meso- and dl-α,β-dibromosuccinic acids. The possibility of
any isomerization of (Z)-stilbene to (E)-stilbene or maleic
acid to fumaric acid has been ruled out by independent reac-
tions of (Z)-stilbene and maleic acid with nickel boride un-
der identical conditions. The debrominations were undoubtedly
due to the involvement of nickel boride generated in situ as
starting meso-stilbene dibromide was recovered unchanged
when treated with nickel chloride or sodium borohydride
separately.
The protection–deprotection of olefins via bromination
and debromination (1) has been studied and different re-
agents and reaction conditions exist for debrominating vic-
dibromides (2–9). Solvolytic stereoselective debromination
has also been reported by DMF (10) and HMPA (11) with-
out the aid of any reagents. The efficiency of a reagent
greatly depends upon its selectivity and compatibility with
other functionalities present in the substrate. Nickel boride is
a versatile reducing agent reported to bring about a number
of transformations, e.g., reduction, deoxygenation, desulfuri-
zation (12). It is known to behave differently under different
reaction conditions and therefore we decided to explore its
application for the debromination and (or) reduction of vic-
dibromides.
Results and discussion
This is the first report on (i) stereoselective debromination
of vic-dibromides to olefins and (ii) debromination with con-
comitant reduction of vic-dibromides in a one-pot reaction
with nickel boride by changing the stoichiometric ratios and
the solvent. Chalcone dibromides (benzylideneacetophenone
dibromides/benzalacetophenone dibromides) also undergo
chemoselective debromination to chalcones or undergo
debromination with concomitant reduction to selectively give
either dihydrochalcones or tetrahydrochalcones in methanol
in one-pot reactions by changing the stoichiometric ratios.
A variety of stilbene dibromides and other vic-dibromides
(Table 1, runs 1–16), soluble in tetrahydrofuran, undergo
NiCl2, NaBH4
THF/MeOH, rt
RCHBr-CHBrR'
RCH = CHR'
[1]
IIa–IIp, IVq, IVa–IVk
Ia–Iq, IIIa–IIIk
Received 20 April 2006. Accepted 1 August 2006. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on
3 October 2006.
J.M. Khurana,1 B.M. Kandpal, G. Kukreja, P. Sharma. Department of Chemistry, University of Delhi, Delhi 110007, India.
1Corresponding author (e-mail: jmkhurana@chemistry.du.ac.in; jmkhurana1@yahoo.co.in).
Can. J. Chem. 84: 1019–1023 (2006)
doi:10.1139/V06-125
© 2006 NRC Canada

1020
Can. J. Chem. Vol. 84, 2006
Table 1. Debromination of vic-dibromides with nickel boride in THF at ambient temperature.
Run
Substrate
Time (min)
Isolated yield (II) (%)
30
40
40
40
120
40
40
60
45
60
60
60
30
60
45
35
1
meso-C6H5CHBrCHBrC6H5 (Ia)
dl-C6H5CHBrCHBrC6H5 (Ib)
96
94
89
88
87
76
96
84
89
90
80
90
75
90
88
90
2
3
meso-4-CH3C6H4CHBrCHBrC6H5 (Ic)
meso-4-ClC6H4CHBrCHBrC6H5 (Id)
meso-4-ClC6H4CHBrCHBrC6H4Cl-4 (Ie)
meso-4-OCH3C6H4CHBrCHBrC6H5 (If)
C6H5CHBrCHBrCOOH (Ig)
4
5
6
7
8
C6H5CHBrCHBrCOOCH3 (Ih)
9
meso-COOHCHBrCHBrCOOH (Ii)
dl-COOHCHBrCHBrCOOH (Ij)
CH2BrCHBr(CH2)3CH3 (Ik)
10
11
12
13
14
15
16
trans-CH2BrCHBr(CH2)5CH2 (Il)
trans-CH2BrCHBr(CH2)3CH2 (Im)
threo-CH3(CH2)7CHBrCHBr(CH2)7COOH (In)
threo-CH3(CH2)7CHBrCHBr(CH2)7COOCH3 (Io)
CH3CHBrCHBrCOOCH3 (Ip)
Note: Seventy-five millilitres of solvent were used per gram of substrate. Molar ratio is 1:2:6 (substrate–NiCl2–NaBH4).
Table 2. Debromination of chalcone dibromides and α,β-dibromoketones with nickel boride in MeOH at ambient temperature.
Run
Substrate
Time (min)
Isolated yield (IV) (%)
17
18
19
20
21
22
23
24
C6H5COCHBrCHBrC6H5 (IIIa)
45
35
20
15
25
40
30
60
90
88
90
92
88
90
90
69
4-CH3C6H4COCHBrCHBrC6H5 (IIIb)
4-ClC6H4CHBrCHBrCOC6H5 (IIIc)
4-ClC6H4COCHBrCHBrC6H4Cl-4 (IIId)
4-OCH3C6H4COCHBrCHBrC6H4CH3O-4 (IIIe)
4-BrC6H4CHBrCHBr COC6H5 (IIIf)
C6H5CHBrCHBrCOCH3 (IIIg)
(IIIh)
O
Br
Br
25
20
92
(Iq)
HO
Br
Br
26
27
45
15
88
90
(IIIi)
CH(Br)CH(Br)COCH3
O
Br
Br
(IIIj)
O
O
28
C6H5CHBrCHBrCOCHBrCHBrC6H5 (IIIk)
35
85
Note: Thirty millilitres of methanol were used per gram of substrate. Molar ratio is 1:5:2 (substrate–NiCl2–NaBH4).
© 2006 NRC Canada

Khurana et al.
1021
Table 3. Reduction of vic-dibromides with nickel boride in MeOH at ambient temperature.
Run
Substrate
Time (min)
Isolated yield (V) (%)
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
meso-C6H5CHBrCHBrC6H5 (Ia)
10
15
15
10
40
25
15
10
20
15
15
20
15
15
15
15
92
94
90
94
83
85
92
82
77
85
85
86
88
91
81
85
dl-C6H5CHBrCHBrC6H5 (Ib)
meso-4-CH3C6H4CHBrCHBrC6H5 (Ic)
meso-4-ClC6H4CHBrCHBrC6H5 (Id)
meso-4-ClC6H4CHBrCHBrC6H4Cl-4 (Ie)
meso-4-OCH3C6H4CHBrCHBrC6H5 (If)
C6H5CHBrCHBrCOOH (Ig)
C6H5CHBrCHBrCOOCH3 (Ih)
meso-COOHCHBrCHBrCOOH (Ii)
CH2BrCHBr(CH2)3CH3 (Ik)
trans-CH2BrCHBr(CH2)5CH2 (Il)
trans- CH2BrCHBr(CH2)5CH2 (Im)
threo-CH3(CH2)7CHBrCHBr(CH2)7COOH (In)
threo-CH3(CH2)7CHBrCHBr(CH2)7COOCH3 (Io)
CH3CHBrCHBrCOOCH3 (Ip)
(Iq)
HO
Br
Br
Note: Fifty millilitres of solvent were used per gram of substrate. Molar ratio is 1:3:9 (substrate–NiCl2–NaBH4).
We also report herein the debromination with concomi-
tant reduction of vic-dibromides with nickel boride gener-
ated in situ. Since the activity, selectivity, and the physical
and chemical properties of nickel boride depend on its method
of preparation, and the amount of H2 adsorbed in the crystal
lattice of nickel boride depends upon the metal–boron ratio
(12), the stoichiometric ratios of substrate–NiCl2–NaBH4
were varied to achieve the goal. vic-Dibromides (Ia–Ii, Ik–
Iq) can be debrominated and reduced concomitantly in a
one-pot reaction with nickel boride using a molar ratio of
1:3:9 in methanol to give the corresponding reduced product
(Table 3, runs 29–44) in high yields (eq. [2]). Reactions of
meso- and dl-stilbene dibromides using molar ratios of 1:2:6
or 1:1:3 of substrate – nickel chloride – sodium borohydride
in methanol resulted in the formation of a mixture of (E)-
stilbene and bibenzyl, implying that the reductions must be
proceeding via the corresponding alkenes. The acid and ester
groups were unaffected under these conditions.
lar ratio of 1:10:15 (substrate–NiCl2–NaBH4). High yields of
dihydrochalcones were obtained under these conditions in
methanol at ambient temperature (eq. [4]) (Table 5, runs 54–
58). p-Bromochalcone dibromide (IIIf) also underwent com-
petitive aryl debromination under these conditions.
O
OH
[3]
NiCl2, NaBH4
MeOH, rt
RCH2CH2-CH-R'
RCHBr-CHBrC-R'
IIIa–IIIe, IIIg–IIIj
VIa–VIe, VIg–VIj
O
O
NiCl2, NaBH4
MeOH, rt
RCH2CH2-C-R'
RCHBr-CHBrC-R'
[4]
IIIa–IIIe
VIIa–VIIe
We conclude that nickel boride is an efficient and versatile
reagent for debromination of vic-dibromides to the corres-
ponding (E)-olefins and for debromination with concomitant
reduction to give dihydro products at ambient temperature.
Chalcone dibromides and other α,β-dibromoketones undergo
debromination with complete reduction to give alcohols or
undergo debromination with selective reduction to give
dihydrochalcones.
NiCl2, NaBH4
MeOH, rt
RCHBr-CHBrR'
Ia–Ii, Ik–Iq
RCH2CH2R'
Va–Vi, Vk–Vq
[2]
Chalcone dibromides and other α,β-dibromoketones gave
corresponding alcohols (eq. [3]) rather than ketones under
these conditions (Table 4, runs 45–53). Reactions of chal-
cone dibromide using molar ratios of 1:1:3 or 1:2:6 were
incomplete and showed the presence of chalcone, dihydro-
chalcone, and tetrahydrochalcone. Selective debromination
and reduction of the double bond could not be achieved un-
der these conditions without affecting the carbonyl group.
However, selective debromination was achieved using a mo-
Experimental
General procedure for reactions of stilbene dibromides
with NiCl2 and NaBH4 (molar ratio 1:2:6, Table 1) in THF
In a typical general procedure, meso-stilbene dibromide
(1 g, 2.94 mmol) was dissolved in THF (75 mL) in a
250 mL round-bottomed flask mounted over a magnetic stir-
© 2006 NRC Canada

1022
Can. J. Chem. Vol. 84, 2006
Table 4. Reduction of chalcone dibromides and α,β-dibromoketones with nickel boride in MeOH to their tetrahydro
derivatives at ambient temperature.
Run
Substrate
Time (min)
Isolated yield (VI) (%)
45
46
47
48
49
50
51
C6H5COCHBrCHBrC6H5 (IIIa)
15
5
91
80
96
83
78
82
83
4-CH3C6H4COCHBrCHBrC6H5 (IIIb)
4-ClC6H4CHBrCHBrCOC6H5 (IIIc)
4-ClC6H4COCHBrCHBrC6H4Cl-4 (IIId)
4-OCH3C6H4COCHBrCHBrC6H4CH3O-4 (IIIe)
C6H5CHBrCHBrCOCH3 (IIIg)
10
10
10
15
10
(IIIh)
O
Br
Br
52
53
45
45
75
75
CH(Br)CH(Br)COCH3
(IIIi)
O
C6H5CHBrCHBrCOCHBrCHBrC6H5 (IIIj)
Note: Forty millilitres of methanol were used per gram of substrate. Molar ratio is 1:3:9 (substrate–NiCl2–NaBH4).
Table 5. Reduction of chalcone dibromides with nickel boride in MeOH to their dihydrochalcones at ambient
temperature.
Run
Substrate
Time (min)
Isolated yield (VII) (%)
54
55
56
57
58
59
C6H5COCHBrCHBrC6H5 (IIIa)
10
10
15
15
10
—
87
86
83
79
82
4-CH3C6H4COCHBrCHBrC6H5 (IIIb)
4-ClC6H4CHBrCHBrCOC6H5 (IIIc)
4-ClC6H4COCHBrCHBrC6H4Cl-4 (IIId)
4-OCH3C6H4COCHBrCHBrC6H4CH3O-4 (IIIe)
4-BrC6H4CHBrCHBrCOC6H5 (IIIf)
a
—
Note: Forty millilitres of methanol were used per gram of substrate. Molar ratio is 1:10:15 (substrate–NiCl2–NaBH4).
aA mixture of dihydrochalcone (56%) and p-bromodihydrochalcone (28%) was obtained.
rer. NiCl2 (1.39 g, 5.88 mmol) was added followed by the
addition of NaBH4 (0.67 g, 17.64 mmol) while vigorously
stirring the solution. The progress of the reaction was moni-
tored by TLC using petroleum ether as eluent. The reaction
was found to be complete in 30 min. The reaction mixture
was filtered through a Celite pad (~1 in, 1 in = 25.4 mm)
and washed with THF (2 × 10 mL). The combined filtrate
was reduced to half and diluted with water (~150 mL). The
product was extracted with ethyl acetate (3 × 15 mL). The
combined extract was dried over anhydr. MgSO4, filtered,
and concentrated on a rotary evaporator to afford a white
solid, which was identified as (E)-stilbene (0.5 g, 96%) with
a mp of 112 °C (lit. value (13a) mp 114 °C) as demonstrated
by the mixed mp, IR, and NMR spectra.
continuous stirring. Disappearance of starting material was
monitored by TLC using petroleum ether – benzene (50:50)
as eluent. The reaction was complete after 45 min. The reac-
tion mixture was filtered through a Celite pad (~1 in) and
washed with methanol (2 × 15 mL). The combined filtrate
was diluted with water (~150 mL) and extracted with ethyl
acetate (3 × 15 mL). The combined extract was dried over
anhydr. MgSO4, filtered, and concentrated on a rotary evap-
orator to yield chalcone (0.508 g, 90%), confirmed with a
mp of 55 °C (lit. value (13b) mp 56–58 °C) as demonstrated
by the mixed mp, IR, and NMR spectra.
Reactions of stilbene dibromides with NiCl2 and NaBH4
(molar ratio 1:3:9, Table 3) in methanol
A mixture of meso-stilbene dibromide (1 g, 2.94 mmol),
methanol (50 mL), and NiCl2 (2.090 g, 8.82 mmol) was
placed in a 100 mL round-bottomed flask and fitted with a
reflux condenser and a guard tube. NaBH4 (1.005 g,
26.46 mmol) was carefully added with continuous stirring.
The progress of the reaction was monitored using petroleum
ether as an eluent. The starting material disappeared in
10 min. The reaction was worked up as in previous proce-
General procedure for reactions of chalcone dibromides
with NiCl2 and NaBH4 (molar ratio 1:5:2, Table 2) in
methanol
In a 100 mL round-bottomed flask mounted over a mag-
netic stirrer was placed a mixture of chalcone dibromide
(1 g, 2.71 mmol), methanol (30 mL), and NiCl2 (3.22 g,
13.55 mmol). NaBH4 (0.206 g, 5.43 mmol) was added with
© 2006 NRC Canada

Khurana et al.
1023
dures. The product obtained was identified to be 1,2-
diphenylethane (0.48 g, 92%) by IR and NMR spectra.
Acknowledgements
We are pleased to acknowledge the financial support for
this work by the Council of Scientific and Industrial Research
(CSIR, New Delhi, India), project No. 01(1567)/99/EMR-II.
BMK and GK also wish to thank CSIR, PS, and the Univer-
sity Grants Commission (UGC), New Delhi, for providing
fellowships.
Reactions of chalcone dibromides with NiCl2 and
NaBH4 (molar ratio 1:3:9, Table 4) in methanol
Chalcone dibromide (1 g, 2.71 mmol), NiCl2 (1.926 g,
13 mmol), and methanol (40) mL were placed in a 100 mL
conical flask fitted with a condenser. The flask was mounted
over a magnetic stirrer. Sodium borohydride (0.929 g,
24.39 mmol) was added very cautiously while vigorously
stirring the solution. The progress of the reaction was moni-
tored by TLC using petroleum ether – benzene (50:50) as
eluent. The starting material disappeared after 15 min and
then the reaction was worked up as in previous procedures.
The product obtained was identified to be tetrahydro-
chalcone (0.50 g, 91%) by IR and NMR spectra.
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