Selective reductive cleavage of 2,3-epoxybromides by the InCl 3-NaBH4 reagent system

Article abstract of DOI:10.1016/j.tetlet.2004.09.120

A combination of sodium borohydride and a catalytic amount of indium(III) chloride in acetonitrile reduces 2,3-epoxybromides to the corresponding allylic alcohols in good yields involving reduction of the bromo moiety followed by selective C-O bond cleavage through a radical process. Several aromatic, cyclic and open-chain bromoepoxides successfully participated in this reaction.

Full text of DOI:10.1016/j.tetlet.2004.09.120

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8579–8581
Selective reductive cleavage of 2,3-epoxybromides by the
InCl3–NaBH4 reagent system
Brindaban C. Ranu,* Subhash Banerjee and Arijit Das
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
Received 5 July 2004; revised 9 September 2004; accepted 16 September 2004
Available online 1 October 2004
Abstract—A combination of sodium borohydride and a catalytic amount of indium(III) chloride in acetonitrile reduces 2,3-epoxy-
bromides to the corresponding allylic alcohols in good yields involving reduction of the bromo moiety followed by selective C–O
bond cleavage through a radical process. Several aromatic, cyclic and open-chain bromoepoxides successfully participated in this
reaction.
ꢀ 2004 Elsevier Ltd. All rights reserved.
R1
The radical cleavage of epoxyhalides is very interesting
from a mechanistic as well as a synthetic viewpoint. In
principle, both carbon–carbon and carbon–oxygen bond
cleavage is possible and with most reagents both type of
cleavages occurred with C–O bond cleavage predomi-
nating. A variety of radical reducing agents such as tri-
butyltin hydride,1a,b triphenyltin hydride,1c samarium
diiodide,1d,e zinc–copper couple under sonication1f,g
have been used although tributyltin hydride is the most
common. However, because of the toxicity of tributyltin
compounds and tedious purification to remove residual
tin compounds, an alternative radical agent avoiding
these drawbacks is required. Recently, chloro indium
hydride (Cl2InH), formed in situ from the combination
of indium(III) chloride and sodium borohydride, has
been found to show great promise as a practical and bet-
ter alternative to tributyltin hydride in the dehalogena-
tion of alkyl halides2a and other radical cyclizations.2b
As part of our continued interest in indium-mediated
reductions,3 we have recently reported several selective
reductions of important functionalities using the
InCl3–NaBH4 reagent system4 and here we disclose the
selective reductive cleavage of a C–O bond in 2,3-epoxy-
bromides using this reducing agent (Scheme 1).
OH
O
NaBH4 / InCl3 (cat)
CH3CN , rt
R1
R
Br
R
Scheme 1.
anhydrous acetonitrile for the necessary period of time
required to complete the reaction. Usual work up with
ether followed by purification by column chromatogra-
phy provided the pure product.
A variety of epoxybromides including aromatic, cyclic
and open-chain systems underwent reductive cleavage
of the carbon–oxygen bonds to give the corresponding
allylic alcohols by this procedure. The results are sum-
marized in Table 1. No C–C bond cleavage was
observed in any of the substrates tested. The terminal
monosubstituted epoxides (entries 13 and 14) produced
the primary alcohols whereas the internal disubstituted
epoxides provided secondary alcohols (entries 1–12).
However, cleavage of trisubstituted epoxybromides
was problematic as the reaction did not proceed further
after reduction of the bromo functionality and thus no
tertiary alcohol was obtained. An iodo epoxide (entry
2) also participated in this reaction. However, this rea-
gent system failed to initiate the process when bromides
or iodides were replaced by xanthates. When the prod-
uct is not a terminal olefin, the (E)-isomer is formed
(entry 4).
The experimental procedure5 is very simple. The epoxy-
bromide was stirred with a solution of sodium borohy-
dride and a catalytic amount of indium(III) chloride in
Keywords: Indium(III) chloride; Sodium borohydride; 2,3-Epoxybro-
mide; Allylic alcohol; Reduction.
*
The reactions are, in general very clean, reasonably fast
and high yielding. As the starting bromo epoxides were
Corresponding author. Tel.: +91 33 24734971; fax: +91 33
24732805; e-mail: ocbcr@iacs.res.in
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.120

8580
B. C. Ranu et al. / Tetrahedron Letters 45 (2004) 8579–8581
Table 1. Reductive cleavage of 2,3-epoxybromides by InCl3/NaBH4
Entry
1
Substrate
Product
Time (h)
6.0
Yield (%)a
82
Ref.
1e
OH
O
Ph
Ph
Br
I
Ph
OH
O
2
3
6.2
6.1
80
80
1e
Ph
OH
O
Br
MeO
MeO
OH
O
Br
4
6.5
75
6
O
O
O
O
Ph
OH
Ph
O
5b
7.3
6.5
62
77
7
8
Ph
Ph
Br
Br
6b
OH
O
Br
7b
6.0
83
9
O
OH
Br
8b
7.0
7.5
6.5
7.0
6.5
7.0
78
77
81
77
85
70
10
11
9
OH
O
Br
9b
O
OH
O
OH
10
11
12b
13
Br
OH
O
9
Br
4
4
O
OH
12
9
2
2
Br
O
HO
Br
Br
O
14
10
50
9
OH
Ph
Ph
a Yields refer to those of pure isolated products characterized by spectroscopic data (IR, 1H and 13C NMR).
b The epoxide used was a mixture of diastereomers.

B. C. Ranu et al. / Tetrahedron Letters 45 (2004) 8579–8581
8581
OH
O
InCl3
1. P Br3
Ph
OH
Ph
Br
NaBH4
Ph
2. m-CPBA
Scheme 2.
Shibata, I.; Baba, A. J. Am. Chem. Soc. 2002, 124, 906–
907.
prepared from allylic alcohols, this method provides an
efficient procedure for the formal 1,3-transposition of
the hydroxyl group (Scheme 2).
3. (a) Ranu, B. C.; Dutta, P.; Sarkar, A. Tetrahedron Lett.
1998, 39, 9557–9558; (b) Ranu, B. C.; Guchhait, S. K.;
Sarkar, A. Chem. Commun. 1998, 2113–2114; (c) Ranu, B.
C.; Dutta, P.; Sarkar, A. J. Chem. Soc., Perkin Trans. 1
1999, 1139–1140; (d) Ranu, B. C.; Dutta, J.; Guchhait, S.
K. J. Org. Chem. 2001, 66, 5624–5626; (e) Ranu, B. C.;
Dutta, J.; Guchhait, S. K. Org. Lett. 2001, 3, 2603–2605;
(f) Ranu, B. C.; Samanta, S.; Guchhait, S. K. J. Org.
Chem. 2001, 66, 4102–4103; (g) Ranu, B. C.; Samanta, S.;
Das, A. Tetrahedron Lett. 2002, 43, 5993–5995.
4. (a) Ranu, B. C.; Samanta, S. Tetrahedron Lett. 2002, 43,
7405–7407; (b) Ranu, B. C.; Das, A.; Hajra, A. Synthesis
2003, 1012–1014; (c) Ranu, B. C.; Samanta, S. Tetrahe-
dron 2003, 59, 7901–7906; (d) Ranu, B. C.; Samanta, S. J.
Org. Chem. 2003, 68, 7130–7132.
For comparison, when 3-phenyl-2,3-epoxybromide
(entry 1) was treated with lithium aluminium hydride
in ether 3-phenyl-2-propanol was obtained via reduction
of the bromo as well as the epoxide moiety by hydride
ion. On the other hand, sodium borohydride in aceto-
nitrile (or methanol) without indium(III) chloride failed
to cause any reaction. Thus, a combination of sodium
borohydride and indium(III) chloride is essential for this
reductive cleavage. Presumably, the indium hydride
(HInCl2) generated by transmetalation between InCl3
and NaBH4 acts as a radical reducing agent2 and initi-
ates the radical process by reduction of the C–Br bond
followed by subsequent opening of the epoxy ring
though selective C–O bond cleavage. The mechanism
for formation of allylic alcohols by radical reaction of
epoxides is well documented in the literature.1d
5. General experimental procedure-represented by the reduc-
tive cleavage of 3-p-methoxyphenyl-2,3-epoxybromide
(entry 3). A solution of indium(III) chloride (45mg,
0.2mmol, 20mol%) and sodium borohydride (78mg,
2mmol) in dry acetonitrile (3mL) was stirred at À10ꢁC
under nitrogen for 30min. To this was added 3-p-
methoxyphenyl-2,3-epoxybromide (243mg, 1mmol) in
acetonitrile (2mL) at that temperature. The reaction
mixture was then allowed to attain room temperature
and stirring was continued until completion of reaction
(TLC). The mixture was then quenched with a few drops
of water and extracted with diethyl ether (3 · 10mL). The
ether extract was washed with brine and dried (Na2SO4).
Evaporation of the solvent left the crude product, which
was purified by column chromatography over silica gel
(hexane–ether 4:1) to provide pure 1-p-methoxyphenyl-
prop-2-ene-1-ol as a pale yellow liquid (132mg, 80%); IR
In conclusion, the indium(III) chloride–sodium borohy-
dride reagent system provides a unique and simple method
for selective reductive cleavage of the carbon–oxygen
bond in 2,3-epoxyhalides via a radical pathways to pro-
duce allylic alcohols in good yields. This transformation
is not possible using conventional nucleophilic hydride
reducing agents. Certainly, this demonstrates the poten-
tial of indium hydride as a radical reducing agent and
has great promise for further useful applications.
1
(neat) 3365, 1641, 1580, 1245cmÀ1; H NMR (300MHz,
CDCl3): d 3.76 (s, 3H), 5.07–5.33 (m, 3H), 5.90–6.08 (m,
1H), 6.88 (d, J = 12.1Hz, 2H), 7.31 (d, J = 12.1Hz, 2H);
13C NMR (75MHz, CDCl3): d 55.5, 75.0, 114.0 (2C),
114.7, 127.9 (2C), 135.4, 140.0, 159.0. Anal. Calcd for
C10H12O2: C, 73.15; H, 7.36. Found: C, 73.27; H, 7.31.
This procedure was followed for the reductive cleavages of
all the substrates listed in Table 1. All products were
characterized by their IR, 1H NMR and 13C NMR
spectroscopic data and were easily identified by compari-
son with those values reported (see references in Table 1).
6. Mondal, P. K.; Maity, G.; Roy, S. C. J. Org. Chem. 1998,
63, 2829–2834.
Acknowledgements
We are pleased to acknowledge the financial support
from CSIR, New Delhi [Grant no. 01(1739)/02] for this
investigation. S.B. and A.D. are also thankful to CSIR
for their fellowships.
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