Stereoselective debromination of aryl-substituted vic-dibromide with indium metal

Article abstract of DOI:10.1039/a806530f

Debromination of both meso and dl (erythro and threo) aryl-substituted vic-dibromides with indium metal in MeOH leads to trans-alkenes exclusively.

Full text of DOI:10.1039/a806530f

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Stereoselective debromination of aryl-substituted vic-dibromide with indium
metal
Brindaban C. Ranu,*† Sankar K. Guchhait and Arunkanti Sarkar
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
Debromination of both meso and dl (erythro and threo) aryl-
substituted vic-dibromides with indium metal in MeOH
leads to trans-alkenes exclusively.
indium products§ from debromonation of erythro-1,2-dibromo-
1-phenyl-2-benzoylethane in MeOH, even after 8 h. The
presence of cis-stilbene was also not detected upon quenching
the debromination reaction of vic-dibromides of stilbene at an
intermediate stage.
In general, the reactions are very clean and high-yielding.
MeOH has been found to be the best solvent for this reaction; in
pure MeCN the debromination does not proceed at all. Several
sensitive functional groups, such as ketone carbonyl, carboxylic
ester, hydroxy, methoxy and chloro groups on aromatic rings,
remained unaffected under the present reaction conditions. No
over-reduction of the produced alkene was observed with any
The protection-deprotection of olefins via bromination-debro-
mination is an important process in organic synthesis. Although
bromination generally proceeds smoothly and stereospecifically
to give high yields of dibromides, debromination at a later stage
in the synthesis often proves more difficult. This is primarily
because the efficiency of this process greatly depends upon the
stereoselectivity in the debromination step and compatibility of
the reagent with the carbon–carbon double bond formed and
other functionalities present in the substrates. Many reagents1
including metals like Zn,1d Mg1d and Sm,1h have been reported
in the literature for this reaction, but most of them are also
associated with the limitations regarding selectivity and com-
patibility. Thus, an efficient and selective procedure for
debromination of vic-dibromides is needed.
Table 1 Debromination of aryl-substituted vic-dibromides with indium
metal in MeOH
Entry
Substrate
t/h
Product
Yield
(%)a
In recent times there has been increasing interest in indium-
mediated transformations because of certain unique properties
inherent to indium.2 However, although indium has been used
extensively in carbonyl addition reactions,2,3 its potential in
other domains has not been explored to any great extent.4
Because of the close resemblance of indium to magnesium and
zinc in several respects, including first ionization potential,
indium could also be a potential reducing agent. This prompted
us to initiate an investigation of indium-promoted reductive
debromination of vic-dibromides. We have observed that aryl-
substituted vic-dibromides undergo smooth debromination to
produce the corresponding (E)-alkenes when treated with
indium metal in MeOH (Scheme 1).
The experimental procedure is very simple. A mixture of vic-
dibromide (1 mmol) and indium metal (1 mmol,‡ cut into small
pieces) in dry MeOH (10 ml) was refluxed for a certain period
of time (Table 1) until completion of the reaction (TLC). MeOH
was removed and the residue was extracted with Et2O.
Evaporation of solvent followed by purification by silica gel
chromatography furnished the pure alkene in high yields.
A wide range of structurally varied aryl-substituted vic-
dibromides underwent debrominations by this procedure to
provide the corresponding alkenes. The results are summarised
in Table 1. Very interestingly, only trans olefins are obtained
from all the substrates, whether they are meso/erythro or dl/
threo (entries 1, 2, 4, 5, 8, 9). If debromination occurs by the
usual trans-elimination, meso/erythro- or dl/threo-vic-di-
bromides would give trans- or cis-alkenes, respectively. It is
therefore suggested that the reaction occurs via a common,
relatively stable radical or anion intermediate which directly
collapses to (E)-alkene. This speculation gains support from the
observations that cis-stilbene does not undergo isomerisation to
the trans isomer upon reflux with indium metal or oxidised
Br
Ph
Ph
1
2
Ph
88
85
2
Ph
Ph
Ph
Br
Br
Br
Br
Ph
8
Ph
Ph
Ph
Me
Me
94
3
7
Ph
Ph
Ph
Br
Br
Br
CO2Me
CO2Me
4b
CO2Me
90
92
4
5
Br
CO2Me
9
Ph
Ph
Br
Br
12b
12
CO2Me
Ph
O
CO2Me
90
89
6
7
O
Br
O
Br
O
Ph
Ph
Me
Ph
Ph
Me
Br
Br
Br
Br
O
O
O
85
88
8
9
2
Ph
Ph
Ph
Ph
O
1c
Ph
Ph
Br
Br
Br
O
O
Ph
2d
Ph
91
10
Br
a
Ar
Ar
Yields refer to pure isolated products fully characterised by spectral and
i
b
analytical methods. The reaction was performed at room temperature
(30 °C) with stirring. c MeOH–MeCN (1:1) was used as solvent instead of
Br
R
R
MeOH to dissolve the vic-dibromide. d MeOH–MeCN (10:1) was used. e
2
Scheme 1 Reagents and conditions: i, In, MeOH, reflux
equiv. of indium were used.
Chem. Commun., 1998
2113

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promoted debromination of vic-dibromides.6 The significant
improvements offered by this method over other existing
debromination procedures1 are: no overreduction of the double
or triple bond formed, tolerance to several reducible functional-
ities, exclusive formation of (E)-alkenes from cis- as well as
trans-dibromides, selective debromination of aryl-substituted
dibromide moieties in presence of alkyl-substituted ones, and
the easy availability and apparently nontoxic nature of indium
metal.¶ Thus, this reaction is endowed with considerable
synthetic potential and may provide a new method for reductive
debromination and conversion of a cis-alkene to its trans-
isomer. Further investigations of more useful applications are in
progress.
We gratefully acknowledge financial support from CSIR,
New Delhi [Grant No. 01(1504)/98] for this investigation.
S. K. G. and A. S. are also thankful to CSIR for their
fellowships. We thank Mr A. Som for his help with this work
during his tenure as a summer project student in this laboratory
from IIT, Kanpur.
Table 1 (cont.) Debromination of aryl-substituted vic-dibromides with
indium metal in MeOH
Entry Substrate
t/h Product
Yield
(%)a
Br
O
O
9c
Ph
Ph
92
11
Cl
Br
Cl
Br
O
O
HO
12
HO
9c
Ph
Ph
86
90
Br
Br
CO2Et
CO2Et
MeO
13
MeO
19
Br
Br
Br
14
12
12
No reaction
Notes and References
Br
H
† E-mail: ocbcr@iacs.ernet.in
15
H
Br
No reaction
‡ Debromination also proceeds in the presence of < 1 equiv. of indium;
however, the reaction is very slow, e.g. erythro-1,2-dibromo-1-phenyl-
2-benzoylethane (entry 8) takes 9 h with 0.5 equiv of In compared to 1 h
with 1 equiv under identical reaction conditions.
MeO2C
CO2Me
Br
Ph
Ph
O
O
§ We thank one of the referees for this suggestion.
¶ Indium metal is not affected by air and moisture and thus does not require
any activation before reaction. Indium can be handled easily without any
special precautionary measures and is relatively inexpensive.
Br
Br
3.5e
86
16
17
Br
O
O
1 (a) E. L. Allred, B. R. Beck and K.J. Voorhees, J. Org. Chem., 1974, 39,
1426; (b) D. Landini, S. Quici and F. Rolla, Synthesis, 1975, 397; (c) D.
Savoia, E. Tagliavini, C. Trombini and A. U. Ronchi, J. Org. Chem.,
1982, 47, 876; (d) E. Baciocchi, in Chemistry of Functional Groups,
Supplement D, Part 1, ed. S. Patai and H. Rappoport, Wiley, New York,
1983; (e) S. G. Davies and S. E. Thomas, Synthesis, 1984, 1027; (f) K.
Yanada, R. Yanada and H. Meguri, J. Chem. Soc., Chem. Commun.,
1990, 730; (g) J. M. Khurana and G. C. Maikap, J. Org. Chem., 1991, 56,
2582; (h) R. Yanada and N. Negoro, K. Yanada and T. Fujita,
Tetrahedron Lett., 1996, 37, 9313; (i) C. Malanga, S. Mannucci and L.
Lardicci, Tetrahedron, 1998, 54, 1021; (j) T. S. Butcher and M. R. Detty,
J. Org. Chem., 1998, 63, 177.
Br
Br
Br
Ph
Br
Br
8.5
7
Ph
C
C
Ph
88
82
Ph
Ph
Br
C
C
Ph
18
a
Yields refer to pure isolated products fully characterised by spectral and
b
analytical methods. The reaction was performed at room temperature
(30 °C) with stirring. c MeOH–MeCN (1:1) was used as solvent instead of
2 P. Cintas, Synlett, 1995, 1087.
MeOH to dissolve the vic-dibromide. d MeOH–MeCN (10:1) was used. e
2
3 C. J. Li, D. L. Chen, Y. Q. Lu, J.-X. Haberman and J. T. Mague, J. Am.
Chem. Soc., 1996, 118, 4216; V. J. Bryan and T. H. Chan, Tetrahedron
Lett., 1996, 37, 5341; T.-P. Loh and X. R. Li, Tetrahedron Lett., 1997, 38,
869; M. B. Isaac and L. A. Paquette, J. Org. Chem., 1997, 62, 5333; X.-H.
Yi, Y. Meng and C.-J. Li, Chem. Commun., 1998, 449.
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equiv. of indium were used.
substrate, unlike those reactions reported using Sm1h and Mg.5
As this reagent is inert to alkyl-substituted dibromides (entries
14, 15), selective debromination of aryl-substituted vic-di-
bromide moieties is achieved in the presence of alkyl-
substituted dibromide moieties (entry 16). This procedure is
also effective for the debromination of vic-dibromoalkenes to
the corresponding alkynes (entries 17, 18).
In conclusion, the present procedure provides an efficient and
general methodology for reductive debromination of aryl-
substituted vic-dibromides to the corresponding (E)-alkenes; to
the best of our knowledge this is the first report of indium-
5 T. Hudlicky, G. Sinai-Zingde and M. G. Natchus, Tetrahedron Lett.,
1987, 28, 5287.
6 For indium promoted debromination of geminal dibromides, see: S. Araki
and Y. Butsugan, J. Chem. Soc., Chem. Commun., 1989, 1286.
Received in Cambridge, UK, 19th August 1998; 8/06530F
2114
Chem. Commun., 1998