Indium-mediated consecutive 1,2-shift reaction and regioselective allylation of vinyl epoxides

Article abstract of DOI:10.1016/S0040-4039(03)00418-0

Allyl indium, prepared from allyl bromide and indium metal in aprotic solvent, reacts with terminal vinyl epoxides at room temperature to afford various bishomoallyl alcohols in moderate to high yields via consecutive 1,2-shift reaction and regioselective

Full text of DOI:10.1016/S0040-4039(03)00418-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2911–2913
Indium-mediated consecutive 1,2-shift reaction and regioselective
allylation of vinyl epoxides
Byung Kyu Oh, Joo Hwan Cha, Yong Seo Cho, Kyung Il Choi, Hun Yeong Koh, Moon Ho Chang
and Ae Nim Pae*
Biochemicals Research Center, Korea Institute of Science and Technology, PO Box 131 Cheongryang, Seoul 130-650,
Republic of Korea
Received 28 January 2003; revised 11 February 2003; accepted 13 February 2003
Abstract—Allyl indium, prepared from allyl bromide and indium metal in aprotic solvent, reacts with terminal vinyl epoxides at
room temperature to afford various bishomoallyl alcohols in moderate to high yields via consecutive 1,2-shift reaction and
regioselective allylation. © 2003 Elsevier Science Ltd. All rights reserved.
The use of organometallic reagents for organic syn-
thetic purpose has been growing in scope and in impor-
tance.1 In particular, organoindium reagents have
attracted much attention due to their compatibility with
many common organic functional groups and stability
under aqueous conditions. Allyl indium reagents, gener-
ated in situ from indium metal with activated halide
(e.g. allyl halide, a-halo ester) in organic solvent is
known to be sesquihalide,2 (allyl)3In2X2 that reacts with
various electrophiles, such as carbonyl compounds to
give homoallyl alcohols. Epoxides are good elec-
trophiles capable of reacting with organometallic
reagents, such as allyl magnesium, allyl zinc and allyl-
silane.3–5 However, most of these reagents are sensitive
to air or moisture in contrast with allyl indium. Vinyl
epoxides are commonly used starting materials in
organic synthesis. Ring opening reaction of vinyl epox-
ides nucleophile goes to two pathways which are 1,4-
nucleophilic addition and 1,2-nucleophilic addition6
(Scheme 1).
We attempted indium mediated regioselective allylation
with vinyl epoxides with various allylbromides via ring
opening reaction. Unexpectedly, we could obtain the
consecutive 1,2-shift reaction to generate terminal alde-
hyde and then allylation products instead of 1,2-addi-
tion or 1,4-addition product (Scheme 2). We extended
this result to the reactions using several kinds of vinyl
epoxides and various allyl bromides.
The 1,2-shift reaction of epoxides to give aldehydes
using indium(III) chloride has been reported.7 The ter-
minal epoxides undergo allylation reaction at less hin-
dered position using indium and allyl bromides without
1,2-shift reaction.8 In the case of vinyl epoxides, alkenyl
group could stabilize the generated carbocation in
migrating intermediate without Lewis acid. Herein we
report a facile and high regioselective method for 1,2-
shift and allylation reaction of vinyl epoxides using
indium.
Firstly, we carried out the reaction of vinyl epoxide and
methyl vinyl epoxide with various allyl bromides in
THF at room temperature (Table 1). We applied two
reaction methods, Grignard type (method a)9 and Bar-
bier type (method b).10 Grignard type reaction is gener-
ally called a method for the generation of allyl indium
before addition of substrates. For the Barbier type,
generation of allyl indium and the allylation reaction
Scheme 1.
* Corresponding author. Tel.: +82-2-958-5185; fax: +82-2-958-5189;
e-mail: anpae@kist.re.kr
Scheme 2.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00418-0

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B. K. Oh et al. / Tetrahedron Letters 44 (2003) 2911–2913
Table 1. Tandem 1,2-shift reaction and allylation of vinyl-
oxirane and methyl vinyloxirane
Table 3. Tandem 1,2-shift reaction and allylation of cyclo-
hexenyloxirane
The reactions of cyclohexenyloxirane were accom-
plished in THF to give two products A and B in high
yield (78–88%) shown in Table 3. In this cyclic alkenyl
system, 1,2-addition reaction was more favorable than
1,2-shift reaction and allylation in ratio of 1–8.7 to 1
(B/A).
Instead of terminal vinyl epoxides, we have tried with
epoxides having heterocyclic ring (Table 4). These reac-
tions gave same products as other vinyl epoxide reac-
tions, 1,2-addition reaction product and tandem
1,2-shift and allylation product. Thiophenyl epoxides
occurred in situ. In this case (Table 1), all the reactions
were accomplished by Grignard type and we could get
single bishomoallyl alcohols (A) in high yield (61–91%).
Exceptionally, 2-bromomethyl acrylate led to homoal-
lylic alcohol which underwent further cyclization to
give lactone (B). We further studied the reactions of
conjugated aromatic vinyl epoxide (Table 2) and cyclo-
hexenyloxirane system (Table 3).
Table 4. Tandem 1,2-shift reaction and allylation of con-
jugated heterocyclic epoxides
When trans-cinnamyloxirane was treated with allyl
indium in DMF, it also produced 1,2-addition reaction
product (B) via inside attack of epoxide as well as
tandem 1,2-shift reaction and allylation product (A) in
ratio of 1.4–8.5 to 1 (A/B). In the case of 2-bromo-
methyl acrylate, no reaction occurred.
Table 2. Tandem 1,2-shift reaction and allylation of trans-
cinnamyloxirane

B. K. Oh et al. / Tetrahedron Letters 44 (2003) 2911–2913
2913
Table 5. Tandem 1,2-shift reaction and propargylation of
various epoxides
5. Dao-Li, D.; Zhong-Hui, L. Youji Huaxue. 1995, 15, 95.
6. Keith, F.; Mark, L. Org. Lett. 2000, 2, 2319.
7. Raun, B. C.; Jana, U. J. Org. Chem. 1998, 63, 8212.
8. Yadav, J. S.; Anjaneyulu, S.; Ahmed, M. M.; Reddy, B.
V. S. Tetrahedron Lett. 2001, 42, 2557.
9. (a) Grignard type reaction (typical procedure, entry 11): A
suspension of indium powder (157.1 mg, 1.36 mmol) and
allyl bromide (248.0 mg, 2.05 mmol) in 2 mL of DMF
was stirred until the metal dissolved completly. To the
allyl indium reagent generated as above, a solution of
2-styryloxirane (100 mg, 0.68 mmol) was added and
stirred for 1.5 h. After completion of the reaction, the
reaction mixture was quenched with 1N HCl and
extracted with methylene chloride. The organic layer was
dried with anhydrous MgSO4 and purified by column
chromatography (ethyl acetate:hexane=1:6) to afford the
products (80.6 mg; 11A, 9.5 mg; 11B, 70%).
Compound 11A: 1H NMR (300 MHz, CDCl3): l 7.32 (m,
5H), 6.51 (d, J=15.9 Hz, 1H), 6.27 (m, 1H), 5.87 (m,
1H), 5.19 (m, 2H), 3.18 (m, 1H), 2.42 (m, 4H); 13C NMR
(75 MHz, CDCl3): l 137.7, 135.0, 133.5, 128.9, 127.7,
126.6, 126.5, 118.5, 70.7, 41.7, 40.8; IR (KBr): 3501, 2940,
1655, 1477 cm−1; HRMS (CI, M−H+) calcd for C13H15O:
187.1123; found: 187.1122.
gave higher ratio of 1,2-shift and allylation than furanyl
epoxides, it might be due to the electron rich sulfur
stabilizing carbocation intermediate.
Compound 11B: 1H NMR (300 MHz, CDCl3): l 7.22 (m,
5H), 6.43 (d, J=15.9 Hz, 1H), 6.00 (dd, J=15.9, 8.5 Hz,
1H), 5.74 (m, 1H), 5.01 (m, 2H), 3.62 (m, 1H), 3.49 (m,
1H), 2.43 (m, 1H), 2.22 (m, 2H); 13C NMR (75 MHz,
CDCl3): l 137.5, 136.5, 132.7, 131.1, 128.9, 127.8, 126.6,
116.9, 66.0, 46.14, 13.6; IR (KBr): 2943, 2904, 2301, 1588,
1480 cm−1; HRMS (CI, M−H+) calcd for C13H15O:
187.1123; found: 187.1119.
Propargylation of several vinyl epoxides were per-
formed with propargyl bromide (Table 5). In these
reactions, we could only obtain tandem 1,2-shift reac-
tion and propargylation or allenylation reaction. In the
case of entry 30, we also obtained a small amount of
further propagylation product C of product A.11
10. (b) Barbier type reaction (typical procedure, entry 20):
2-Oxiranylfuran (100 mg, 0.91 mmol) is added to the
solution of indium powder (208.5 mg, 1.82 mmol) and
allyl bromide (351.4 mg, 2.72 mmol) in 2 mL of THF and
stirred for 1 h. After completion of the reaction, the
reaction mixture was quenched with 1N HCl and
extracted with methylene chloride. The organic layer was
dried with anhydrous MgSO4 and purified by column
chromatography (ethyl acetate:hexane=1:7) to afford
products (70.6 mg; 20A, 46.8 mg; 20B, 85%).
In summary, we have described a facile and highly
efficient consecutive 1,2-shift reaction and allylation of
vinyl epoxides using indium metal and allylbromide or
propagyl bromide to afford bishomoallyl alcohols in
high yields.
Acknowledgements
This work was financially supported by the Korea
Ministry of Science and Technology (Critical
Technology-21).
1
Compound 20A: H NMR (300 MHz, CDCl3): l 7.27 (t,
J=1.0 Hz, 1H), 6.24 (t, J=2.6 Hz, 1H), 6.04 (d, J=3.1
Hz, 1H), 5.70 (m, 1H), 5.09 (m, 2H), 3.90 (m, 1H), 2.76
(m, 2H), 2.20 (m, 2H); 13C NMR (75 MHz, CDCl3): l
153.0, 142.0, 134.8, 118.5, 110.7, 107.4, 69.9, 41.5, 35.8;
IR (KBr): 3450, 2940, 2804, 1588 cm−1; HRMS (CI,
M−H+) calcd for C9H11O2: 151.0759; found: 151.0758.
References
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Compound 20B: H NMR (300 MHz, CDCl3): l 7.28 (t,
J=1.0 Hz, 1H), 6.24 (t, J=2.9 Hz, 1H), 6.05 (dd, J=3.2,
0.5 Hz, 1H), 5.68 (m, 1H), 4.98 (m, 2H), 3.70 (m, 2H),
2.93 (m, 1H), 2.35 (m, 2H); 13C NMR (75 MHz, CDCl3):
l 156.1, 141.9, 136.1, 117.4, 110.4, 106.7, 65.0, 42.0, 34.8;
IR (KBr): 3454, 2840, 2804, 1608 cm−1; HRMS (CI,
M−H+) calcd for C9H11O2: 151.0759; found: 151.0755.
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