In/InCl3-mediated 1,2-addition of allyl group to α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1081/SCC-120020201

In/InCl₃-mediated addition of allyl iodide to α,β-unsaturated carbonyl compounds gave moderate to high yields of 1,2-addition products. The reactions covered acylic and cyclic α,β-unsaturated carbonyl compounds. Indium trichloride was effective

Full text of DOI:10.1081/SCC-120020201

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In/InCl3-Mediated 1,2-Addition of Allyl Group to α,β-
Unsaturated Carbonyl Compounds
Hye Yeon Kim a b , Kyung Il Choi a , Ae Nim Pae a , Hun Yeong Koh a , Jung Hoon Choi b & Yong
Seo Cho a
a Biochemicals Research Center, Korea Institute of Science and Technology, Cheongryang,
Seoul, Korea
b Department of Chemistry, Hanyang University, Sungdong-Gu, Seoul, Korea
Published online: 17 Aug 2006.
To cite this article: Hye Yeon Kim , Kyung Il Choi , Ae Nim Pae , Hun Yeong Koh , Jung Hoon Choi & Yong Seo Cho (2003):
In/InCl3-Mediated 1,2-Addition of Allyl Group to α,β-Unsaturated Carbonyl Compounds, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:11, 1899-1904
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 11, pp. 1899–1904, 2003
In/InCl3-Mediated 1,2-Addition of Allyl Group to
a,b-Unsaturated Carbonyl Compounds
Hye Yeon Kim,1,2 KyungIl Choi, Ae Nim Pae,1
1
1
Hun YeongKoh, JungHoon Choi, and YongSeo Cho
2
1,
*
1Biochemicals Research Center, Korea Institute of
Science and Technology, Cheongryang, Seoul, Korea
2Department of Chemistry, Hanyang University,
Sungdong-Gu, Seoul, Korea
ABSTRACT
In/InC13-mediated addition of allyl iodide to a,b-unsaturated
carbonyl compounds gave moderate to high yields of 1,2-addition
products. The reactions covered acylic and cyclic a,b-unsaturated
carbonyl compounds. Indium trichloride was effective for these
Barbier-type allylation reactions.
Key Words: Indium; Indium trichloride; 1,2-Addition; Allylation.
*Correspondence: Yong Seo Cho, Biochemicals Research Center, Korea Institute
of Science and Technology, P.O. Box 13R Cheongryang, Seoul 130-650, Korea;
Fax: þ82-2-958-5189; E-mail: ys4049@kist.re.kr.
1899
DOI: 10.1081/SCC-120020201
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1900
Kim et al.
Indium-mediated reactions play a significant role in carbon–carbon
bond formation, and arewidely applied to preparehomoallylic alcohols.
Although much attention has focused on the allylation of carbonyl
compounds, to our best knowledge, there are only a few examples of
study on 1,2-allylation to a,b-unsaturated carbonyl compounds such as
trans-cinamaldehyde, 3,7-dimethyl-2,6-octadiene carboxaldehyde.[1–3]
Herein, we wish to report the indium-mediated 1,2-addition of allyl
group to a,b-unsaturated carbonyl compounds in the presence of
indium trichloride(Sch. 1).
For the examination of allylation of conjugated carbonyl compounds
in acyclic system, 1-acetyl cyclohexene was chosen. In general, indium-
mediated allylations and combination of allylindium and Lewis acid[4] to
carbonyl compounds undergo smoothly in aqueous media via Barbier
[5]
typereaction.
At the first attempt, however, no reaction occurred in
aqueous media such as water, aqueous ethanol, and aqueous THF. In
anhydrous THF, 1,2-addition product was only given in 36% yield. Next,
several additives such as lanthanium triflate, indium tnflate, cupper triflate,
and indium trichloride in the THF solution were examined. Encouragingly,
indium trichloride gave the dramatic improvement of reaction yields
(89%). La(OTf )3 is also effective for the reaction to give 71% yield.
But In(OTf )3 and Cu(OTf )2 were not so effective for the reaction. After
a survey of the amount of indium chloride (0.05 to 1 equiv. based on
substrate), the highest yield (89%) was obtained by applying 1.0 equiv.
of InC13.
Theresults of the1,2-addition of allyl iodideto thecyclic and acyclic
a,b-unsaturated carbonyl compounds using indium and indium trichlor-
ide were summarized in Table 1. The reactivities of the a,b-unsaturated
carbonyl compounds were dependent upon the nature of the substrate.
The reactions of ketones (Entries 1–5) smoothly underwent in THF or
DMF solution. However, in the cases of cyclic ketones, the solvent played
crucial role. Most of the cyclic compounds gave much-improved yields in
DMF than THF except Entries 5 and 6. Especially, 3-methyl-2-cyclo-
hexen-l-one (Entry 8), 2-cyclopenten-l-one (Entry 11), and 2-methyl-2-
cyclopenten-l-one (Entry 12) did not afford the desired products in THF.
Scheme 1.

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In/InCl3-Mediated 1,2-Addition of Allyl Iodide
1901
Table 1. 1,2-Addition of allyl group to a,b-unsaturated carbonyl compounds.a
Yield (%)
Entry
1
SubstrateProduct
Time(h)
1
A
Time(h)
1
B
96
61
2
3
3
90
99
3
1
93
85
0.5
4
5
4
98
75
0.5
4
46
89
1.5
6
7
2
2
61
92
4
75
30
0.5
8
9
4
4
54
90
2
5
0
44
10
2
99
4
77
11
12
2
61
1
1
0
0
1.5
55b
Method A: Isolated yield using DMF as solvent; Method B: Isolated yield using
THF as solvent.
aAll reactions were carried out in 1.0 mmol scale.
bThis reaction was carried out at ꢀ5–0ꢁC.

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1902
Kim et al.
In the case of 2-methyl-2-cyclopenten-1-one (Entry 12), the 1,2-addition
product could only be obtained under low temperature (ꢀ5–0ꢁC).
In conclusion, thereaction of allyl iodideto a,b-unsaturated carbonyl
compounds using indium and indium trichloridegavemoderateto high
yields of 1,2-allylation products.
EXPERIMENTAL
1H NMR spectra were obtained on Varian Gemini 300 and Bruker
Avance 300 spectrometers. Chemical shifts were reported in ppm.
Infrared spectra were obtained on Perkin Elmer 16FPC FT-IR
spectromter. GC/MS spectra were obtained on Hewlett Packard 5890.
Analytical thin layer chromatographies (TLC) were carried out on
precoated silica gel plates (Merck Kieselgel 60F254, layer thickness
0.25 mm). Flash column chromatography was conducted with silica gel 60
(Merck, 230–400 mesh).
Typical Experimental Procedure
Method A: 2-Cyclohex-l-enyl-pent-4-en-2-ol (5): A mixtureof 1-acetyl-
1-cyclohexene (128 mg, 1 mmol), allyl iodide (183 mL, 2 mmol), indium
powder (171 mg, 1.5 mmol), and indium trichloride (226 mg, l mmol) in
freshly distilled tetrahydrofuran (2 mL) was stirred at room temperature
for 4 h. The reaction mixture was quenched with 0.5 mL of 1 N HCl, then
filtered through celite and it was washed with ethyl acetate. The filtrate was
neutralized with saturated sodium bicarbonate solution (pH ¼ 6), then
organic layer was washed with brine, dried over anhydrous magnesium
sulfate. Then the solvent was evaporated off under reduced pressure. The
residue was purified on neutral alumina (ether:hexane ¼ 1:10 to 1:5) to give
148 mg (89%) of product as a light yellow oily compound. Rf ¼ 0.36
(EtOAc:Hexane ¼ 1:6). 1H NMR (300 MHz, CDC13): ꢀ 5.77–5.66 (m, 2H),
5.11 (m, 2H), 2.25 (dd, J ¼ 8.4 Hz, 1H), 2.05 (m, 4H), 1.62 (m, 4H),
1.29 (s, 3H) ppm. 13C NMR (75 MHz, CDC13): ꢀ 142.39, 134.53, 120.54,
118.98, 74.55, 45.42, 27.49, 25.46, 25.28, 23.46, 22.75 ppm. MS
(m/e): 148 (Mþ–H2O), 125 (basepaek); IR (KBr): 3388, 2932, 1658,
1372, 918 cmꢀ1
.
1-Allyl-2-methyl-cyclopent-2-enol (12): A mixtureof 2-mtehyl-2-
cyclopenten-1-one (98 mg, 1 mmol), allyl iodide (183 mL, 2 mmol),

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In/InCl3-Mediated 1,2-Addition of Allyl Iodide
1903
indium powder (171 mg, 1.5 mmol), and indium trichloride (221 mg,
l mmol) in freshly distilled N,N-dimethylforamide (2 mL) was stirred at
ꢀ5–0ꢁC for 1.5 h. The reaction mixture was quenched with 0.5 mL 1 N
HCl, then filtered through celite and the celite, pad was washed with
ethyl acetate. The organic layer was neutralized with saturated sodium
bicarbonatesolution (pH ¼ 6), then rewashed with brine, dried over
anhydrous magnesium sulfate. Then the solvent was evaporated off in
vacuum. The residue was purified on neutral alumina (dilute with ether:
hexane ¼ 1:10, 1:5) to give76 mg (55%) as a light yellow oily compound.
l
Rf ¼ 0.35 (EtOAc:hexane ¼ 1:6). H NMR (300 MHz, CDC13): ꢀ 5.78
(m, 1H), 5.50 (s, 1H), 5.17–4.99 (m, overlap, 2H), 2.46–2.09 (m, 3H),
1.82 (m, 1H), 1.69 (s, 3H), 1.62 (m, 2H) ppm.
Method B: 2-Cyclohex-1-enyl-pent-4-en-2-ol (5): A mixtureof
1-acetyl-1-cyclohexene (128 mg, 1 mmol), allyl iodide (183 mL, 2 mmol),
indium powder (171 mg, 1.5 mmol) and indium trichloride (226 mg,
1 mmol) in N,N-dimethylforamide (2 mL) was stirred at room tempera-
ture for 1.5 h. The reaction mixture was quenched with 0.5 mL of 1 N HCl,
then filtered through celite and it was washed with ethyl acetate. The
filtrate was neutralized with saturated sodium bicarbonate solution
(pH ¼ 6), then organic layer was washed with brine, dried over anhydrous
magnesium sulfate. Then the solvent was evaporated off under reduced
pressure. The residue was purified on neutral alumina (ether:hexane ¼
1:10 to 1:5) to givea light yellow oily compound (148 mg, 89%).
ACKNOWLEDGMENT
This project was financially supported by the Korea Ministry of
Science and Technology (Critical technology 21) and Korea Institute of
Science and Technology.
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4. Wang, R.; Lim, C.; Tan, C.; Lim, B.; Sim, K.; Loh, T. Tetrahedron
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1904
Kim et al.
5. (a) Li, C.J.; Chan, T.H. Organic Reactions in Aqueous Media; John
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Received in Japan February 17, 2002