Indium-mediated regioselective allylation of terminal epoxides: A facile synthesis of bishomoallyl alcohols

Article abstract of DOI:10.1016/S0040-4039(01)00112-5

Allyl indium, prepared from allyl bromide and indium metal in THF, reacts with terminal epoxides at room temperature to afford the corresponding bishomoallyl alcohols in excellent yields and with good regioselectivity.

Full text of DOI:10.1016/S0040-4039(01)00112-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2557–2559
Indium-mediated regioselective allylation of terminal epoxides:
a facile synthesis of bishomoallyl alcohols†
J. S. Yadav,* S. Anjaneyulu, Md. Moinuddin Ahmed and B. V. Subba Reddy
Organic Division I, Indian Institute of Chemical Technology, Hyderabad-7, India
Received 10 November 2000; revised 13 January 2001; accepted 17 January 2001
Abstract—Allyl indium, prepared from allyl bromide and indium metal in THF, reacts with terminal epoxides at room
temperature to afford the corresponding bishomoallyl alcohols in excellent yields and with good regioselectivity. © 2001 Elsevier
Science Ltd. All rights reserved.
Organometallic compounds have acquired considerable
importance in carbonꢀcarbon bond forming reactions.1
In particular, organoindium reagents have attracted
much attention due to their compatibility with many
common organic functional groups (e.g. R-OH, CO2R)
and stability under aqueous conditions. Allyl indium
reagents,2 generated in situ from allyl halides and
indium metal, react with various electrophiles, such as
carbonyl compounds, CꢁN unsaturated systems, CꢀC
multiple bonds, acyl halides, aryl halides, and a,b-
unsaturated compounds, to generate homoallyl prod-
ucts. Aqueous solvents have proved to be most effective
for indium mediated reactions3 and in certain cases
significant regio-, diastereo- and even enantioselectivi-
ties have been achieved. Epoxides are good elec-
trophiles capable of reacting with organometallic
reagents,4–6 such as allyl magnesium, allyl zinc, allylsi-
lane, allylstannane and allylcuprate, to generate unsatu-
rated alcohols. However, most of these reagents are
expensive, sensitive to both air and moisture, and also
some of them require promoters to initiate a reaction.
Further, many of these procedures suffer from low
regioselectivity, unsatisfactory yields and the formation
of side products. The problems associated with these
reagents can be overcome by the use of allylindium for
this transformation. To the best of our knowledge this
is the first report on the allylation of terminal epoxides
with indium metal and allylbromide.
In a continuation of our work on the applications of
indium for various transformations,7 we report here a
novel and highly regioselective method for the allyla-
tion of terminal epoxides using indium metal and allyl-
bromide in THF. The reaction of styrene oxide with
allylindiumbromide at room temperature in THF gave
the corresponding products 2 and 3 in 90% yield
(Scheme 1).8
Scheme 1.
Similarly, several epoxides were treated with allylin-
dium to generate bishomoallyl alcohols in high yields.
The reactions proceeded smoothly at room tempera-
ture with high regioselectivity. The regioselectivity of
this reaction may be explained by the nucleophilic
attack on the less hindered carbon atom of the terminal
epoxide. The results, as summarized in Table 1, clearly
reveal the scope and generality of the reaction with
respect to various epoxides. The reactions were clean
and highly regioselective, affording the corresponding
alcohol 2 with only a trace of the other isomer 3 (Table
1). The epoxides used in this study were prepared by a
known literature method. However, the reaction of
allylindium with mono-substituted terminal epoxides
afforded the product as a mixture of 2 and 3 whereas
disubstituted terminal epoxide gave the product as sin-
gle isomer 2. The ratio of products 2 and 3 was
Keywords: epoxides; indium metal; allyl bromide; unsaturated alco-
hols.
* Corresponding author. Tel.: +91-40-7170512; fax: +91-40-7170512;
e-mail: yadav@iict.ap.nic.in
1
determined by H NMR spectroscopy and GLC analy-
†
IICT Communication No. 4670.
sis. Further, cyclic epoxides like cyclohexene oxide and
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00112-5

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J. S. Yada6 et al. / Tetrahedron Letters 42 (2001) 2557–2559
Table 1. Indium-mediated conversion of epoxides to bishomoallyl alcoholsa
cyclooctene oxide, did not yield any product after a
long reaction time at room temperature. The solvent
THF is the one of choice, as the best results were
obtained. Unlike many zinc- and tin-promoted reac-
tions that use acid catalysts, heat or sonication for
inducing the reaction, this reaction proceeds smoothly
and rapidly at room temperature and does not require
any promoter, stringent conditions, anhydrous solvent
or an inert atmosphere. Even though this reaction
proceeded smoothly in commercial THF (containing
0.2% of water), the reaction was unsuccessful in water
alone. Among various metals such as Sm, Mg, Zn and
Sn studied for this transformation indium is found to
be effective in terms of conversion and reaction time.
In summary, we have described a novel and highly
efficient protocol for the allylation of terminal epoxides
using indium metal and allylbromide in THF. The

J. S. Yada6 et al. / Tetrahedron Letters 42 (2001) 2557–2559
2559
procedure offers several advantages including high
regioselectivity, improved yields, cleaner reactions, sim-
ple experimental and work-up procedures, which make
it a useful and attractive strategy for the synthesis of
bishomoallylic alcohols.
J.; Nishida, S. J. Org. Chem. 1990, 55, 4849.
6. Dao-Li, D.; Zhong-Hui, L. Youji Huaxue. 1995, 15, 95.
7. (a) Yadav, J. S.; Subba Reddy, B. V.; Kiran Kumar
Reddy, G. S. Tetrahedron Lett. 2000, 41, 2695; (b) Yadav,
J. S.; Srinivas, D.; Reddy, G. S.; Bindu, K. H. Tetrahedron
Lett. 1997, 38, 8745; (c) Yadav, J. S.; Subba Reddy, B. V.;
Murilidhar Reddy, M. Tetrahedron Lett. 2000, 41, 2663.
8. In a typical procedure a suspension of indium powder (5
mmol) and allyl bromide (6 mmol) in 10 ml of THF was
stirred until the metal dissolved completely to form a clear
solution. To the allyl indium reagent generated as above, a
solution of styrene oxide (5 mmol) in THF (5 ml) was
added. The resulting reaction mixture was stirred for 3 h at
room temperature. After completion of the reaction, as
indicated by TLC, the reaction mixture was quenched with
saturated ammonium chloride (10 ml) and extracted twice
with ether (2×20 ml). The combined organic layers were
washed with brine, dried over anhydrous Na2SO4, concen-
trated in vacuo and purified by column chromatography
on silica gel (Merck, 60–120 mesh, ethyl acetate:n-hexane,
1:9) to afford product in 90% yield as a colorless liquid.
Representative spectroscopic data for compound 2a: 1H
NMR (CDCl3) l: 1.80 (brs, OH), 2.25 (m, 2H), 2.75 (m,
2H), 3.80 (m, 1H), 5.15 (m, 2H), 5.80 (m, 1H), 7.25 (m,
5H). IR (neat) w: 3450, 3150, 2980, 1620, 1580, 1020, 970.
3a: 1H NMR (CDCl3) l: 2.40 (m, 2H), 2.60 (brs, OH),
2.85 (m, 1H), 3.70 (m, 2H), 5.05 (m, 2H), 5.75 (m, 1H),
7.25 (m, 5H). EIMS (m/z): 162 (M+).
Acknowledgements
S.A, M.M.A. and B.V.S.R. thank the CSIR, New
Delhi, for the award of fellowships.
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