Formation of homoallylic bromohydrins in indium-mediated allylation reactions of phenacyl bromides in aqueous solution

Article abstract of DOI:10.1016/j.tet.2013.07.012

A method is described for carrying out indium-mediated allylation reactions of phenacyl bromides in aqueous solution that form homoallylic bromohydrins. By employing subsequent base treatment, the homoallylic bromohydrins were converted to allylic epoxide

Full text of DOI:10.1016/j.tet.2013.07.012

Tetrahedron 69 (2013) 8263e8268
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Formation of homoallylic bromohydrins in indium-mediated
allylation reactions of phenacyl bromides in aqueous solution
*
Mei-Huey Lin , Chung-Kai Kuo, Wei-Cheng Lin, Yen-Chih Huang, Yu-Ting Tsai,
Kung-Yu Liang, Yi-Syuan Li, Tsung-Hsun Chuang
Department of Chemistry, National Changhua University of Education, Changhua 50007, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 May 2013
Received in revised form 3 July 2013
Accepted 5 July 2013
Available online 16 July 2013
A method is described for carrying out indium-mediated allylation reactions of phenacyl bromides in
aqueous solution that form homoallylic bromohydrins. By employing subsequent base treatment, the
homoallylic bromohydrins were converted to allylic epoxides. Finally, the process has been used as a key
step in a concise sequence for the synthesis of 3-allylbenzofuran.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Indium
Phenacyl bromides
Homoallylic bromohydrins
Epoxides
Allylation
1. Introduction
magnesium are employed in allylation of a-bromocarbonyl com-
pounds, epoxides are produced as major products.8 To the best of
our knowledge, a metal-mediated Barbier type process trans-
Because water is readily available and environmentally benign,
considerable attention has been given to its employment as a sol-
vent for organic chemical reactions.1 In particular, metal-mediated
CeC bond forming reactions occurring in aqueous media have been
intensively investigated.2 While bromohydrins and their homo-
allylic counterparts are useful building blocks in synthetic organic
chemistry,3 only a few examples exist in which direct allylation
forming
a-bromoketones to homoallylic bromohydrins has not
been described to date. In continuation of our efforts aimed at the
development of CeC bond forming reactions in water,9 we explored
the use of phenacyl bromides as substrates in aqueous metal-
mediated Barbier type allylation reactions that form highly func-
tionalized homoallylic bromohydrins.
reactions of
form homoallylic bromohydrins in good yields.4 Although indium-
mediated aqueous allylation reactions of -chlorocarbonyl com-
a-bromocarbonyl compounds have been employed to
2. Results and discussion
a
pounds to form homoallylic chlorohydrins have been reported,5 the
scope of the reaction is limited by the low availability of the phe-
nacyl chloride substrates. In contrast, phenacyl bromides are
readily available and the formed homoallylic bromohydrins should
be useful and versatile substrates in organic synthesis. The results
of a previous effort showed that diallylation products are produced
This effort began with an investigation of metal-mediated ally-
lation reactions of phenacyl bromide (1a) with allyl bromide, in
which various metals were screened for their reactivity in aqueous
solution. The conditions employed and the results of the reactions
are presented in Table 1. The results showed that only indium is
useful in promoting this process in an efficient and functional group
tolerant manner.10
when indium is employed to mediate allylation reactions of
a-
bromocarbonyl compounds (phenacyl bromides) in THF.6 The
homoallylic bromohydrins can be obtained through indium-
It has been reported that reaction of indium with allyl halides
is easier than that with a
-halo carbonyl compounds at rt.2 Owing
mediated allylation of a
-diazocarbonyl compounds in THF.7 How-
to concern about competitive reductive dehalogenation reactions,
a minimum amount of indium was utilized in an exploratory
effort probing solvent effects on the allylation reaction of phe-
nacyl bromide (1a) with allyl bromide to form homoallylic bro-
mohydrin 2a. The results (Table 2) show that although 2a was
ever, when metals with high nucleophilicity such as zinc or
* Corresponding author. Tel.: þ886 4 7232105x3543; fax: þ886 4 7211190; e-mail
address: mhlin@cc.ncue.edu.tw (M.-H. Lin).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.012

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M.-H. Lin et al. / Tetrahedron 69 (2013) 8263e8268
Table 1
Table 3
Metal screeninga
Indium-mediated allylation reactions of phenacyl bromidesa
Ar
O
Ph
O
In
Br
Br
Metal
THF H
Br
+
Br
Ar
Br
Br
+
THF/H2O
rt
OH
Ph
1
2
/
O
(3/1)
2
rt
H
O
2a
1a
Entry
1
Substrate
Product
Yielda (%)
78
Entry
Metal
Reaction time (h)
Yield (%)
O
OH
1
2
3
4
5
Indium
14
8
12
12
12
58
0
0
0
0
Br
1a
Zinc dust
Bismuth
Gallium
Br
2a
O
OH
Aluminium
Br
2
3
4
5
95
73
86
96
a
Conditions: 1a (1.0 mmol), allyl bromide (2.0 mmol) and indicated metal
Br
1b
2b
Me
Me
MeO
Br
(1.0 mmol) in THF (1.5 mL)/water (0.5 mL) at rt.
O
OH
Br
formed when water was used as solvent, the process was sluggish
and did not proceed to completion even after 8 h (Table 2, entry
1). Moreover, no reaction took place in THF11 (Table 2, entry 2)
but when a mixture of THF and water was employed as solvent,
reaction took place to completely consume 1a and form the de-
sired product in moderate isolated yield (Table 2, entries 3 and 4).
THF/H2O (1:3) was found to be the optimum solvent system for
the allylation reaction, which affords the desired product in good
yield along with trace amounts of starting material and the re-
duction product, acetophenone (Table 2, entry 5). In contrast to
Yadav’s results giving diallylation product,6 homoallylic bromo-
hydrin 2a was obtained as the only product in 80% when the
optimum solvent system (THF/H2O¼1:3) was applied (Table 2,
entry 6). It is likely that the nucleophilicity of the allylindium
species generated in aqueous media differs from that in Yadav’s
condition.12
Br
1c
2c
MeO
Br
O
O
OH
Br
Br
1d
2d
OH
Br
Br
1e
2e
Cl
Cl
O
OH
Br
6
88
85
98
96
81
Br
1f
2f
OH
O
OH OH
Br
1g
7
Br
OH
2g
O
O
O
NC
Br
Br
NC
Br
Table 2
8
Solvent optimization studiesa
Br
1h
2h
Ph
O
In
solvent
rt
OH
Br
Br
Br
+
Br
Ph
9
OH
Br
1i
2i
1a
2a
OH
Entry
Solvent
Reaction time (h)
Yield (%)
HO
Br
HO
1
2
H2O
8
8
69b
0
10
THFc
Br
1j
2j
3
4
THF/H2O (1:1)
THF/H2O (3:1)
THF/H2O (1:3)
THF/H2O (1:3)
15
14
14
24.5
67
58
78
80
OMe O
OMe
OMe OH
Br
5
6d
11
99
78
Br
1k
2k
a
Conditions: 1a (1.0 mmol), allyl bromide (2.0 mmol) and indium metal
OMe
(1.0 mmol) in solvent (2.0 mL) at rt.
b
O
OH
No isolation was performed and conversion (%) was given due to separation
12
Br
issues.
c
Commercially available THF contains trace amount of water.
Condition: 1a (1.0 mmol), allyl bromide (2.5 mmol) and indium metal
Br
1l
2l
d
O2N
O2N
(2.5 mmol) in solvent (2.0 mL) at rt.
a
Conditions:
1
(1.0 mmol), allyl bromide (2.0 mmol), and indium metal
(1.0 mmol) in THF (0.5 mL)/water (1.5 mL) at rt.
The results of an investigation exploring the scope of this in-
dium promoted allylation process, show that under the optimized
conditions a variety of aryl ring substituted phenacyl bromide de-
rivatives are converted to the corresponding homoallylic bromo-
hydrins in moderate to excellent yields (Table 3). It is worthy to
note that none or trace amount of the reductive dehalogenation
products are formed in all of the reactions in Table 3.
We also probed the outcome of this allylation process when it is
followed by addition of aqueous sodium hydroxide to the crude
reaction mixture. We observed that this one-pot operation pro-
duces even labile epoxides efficiently (Table 4).
To demonstrate a synthetic application of the methodology,
bromohydrin (2g), formed from ortho-hydroxyphenacyl bromide
(1g), was converted to 3-allylbenzofuran (3g) in high yield via
a two-step sequence involving sequential base and acid treatment
(Eq. 1). Many substances containing the benzofuran motif are
known to be biologically active. Preparation of 3-allylbenzofuran
employing different approaches has been reported.13 Thus, the
method described above provides an alternative route to access 3-
allylbenzofuran (3g).

M.-H. Lin et al. / Tetrahedron 69 (2013) 8263e8268
8265
4. Experimental section
4.1. General
acetone,rt
2) cat. TsOH,PhH,reflux
82% 2 steps
H
O
OH
Br
ð1Þ
O
2g
3g
All commercially available chemicals were used without further
purification. TLC analyses were run on a TLC glass plate (Silica gel 60
F254) and were visualized using UV and a solution of phosphomo-
lybdic acid in ethanol (5 wt %) or p-anisaldehyde stain. Flash
chromatography was performed using silica gel (70e230 mesh). 1H
and 13C NMR spectra were recorded on a 300 MHz spectrometer.
Table 4
One-pot epoxide formation from phenacyl bromidesa
Chemical shifts are reported relative to CHCl3 [dH 7.24, dC (central
OH
O
1) In, allyl bromide
2) NaOH
line) 77.0]. Mass spectra were recorded under atmospheric pressure
chemical ionization (APCI) or electron spray interface (ESI) condi-
tions. High-resolution mass spectra were recorded by orbitrap mass
spectrometer or electron spray interface (ESI) conditions with
a magnetic sector analyzer.
Br
Ar
Ar
O
THF/H2O
rt
THF/H2O
rt
Br
2
Ar
3
1
Entry
1
Substrate
Product 3
Yielda (%)
O
O
Br
4.2. Synthesis
77
1a
3a
4.2.1. General procedure for indium-mediated allylation reactions of
O
O
a-bromoketones. A mixture of allyl bromide (2.0 mmol), indium
Br
2
3
4
5
76
75
79
81
powder (1.0 mmol), and -bromoketone (1.0 mmol) in THF/H2O
a
1b
3b
Me
MeO
Br
Me
(0.5 mL:1.5 mL) was stirred at ambient temperature. Reaction was
monitored by TLC until no starting material was observed and
normally the reaction mixture was stirred at rt overnight. The re-
action mixture was then extracted with Et2O (5 mLꢀ2). The com-
bined organic layers were washed with brine (3 mLꢀ2), dried over
MgSO4, and concentrated in a rotary evaporator. The residue was
purified by silica-gel chromatography using Et2O/hexanes (1:20) as
eluent to give the product.
O
O
Br
1c
3c
MeO
Br
O
O
O
Br
1d
3d
O
4.2.1.1. 1-Bromo-2-phenylpent-4-en-2-ol (2a). Following the
general procedure, the title compound was obtained (188 mg, 78%).
An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.45; 1H NMR (300 MHz, CDCl3)
Br
1e
3e
Cl
Cl
d
2.55 (s, 1H), 2.72 (dd, J¼6.6, 0.9 Hz, 2H), 3.75 (d, J¼10.5 Hz, 1H),
O
O
3.77 (d, J¼10.5 Hz, 1H), 5.05e5.14 (m, 2H), 5.50e5.64 (m, 1H),
Br
7.25e7.39 (m, 5H); 13C NMR (75 MHz, CDCl3)
d
44.5 (CH2), 44.8
6
7
8
9
77
84
76
73
(CH2), 74.6 (C), 119.6 (CH2), 125.3 (CHꢀ2), 127.4 (CH), 128.3 (CHꢀ2),
132.4 (CH), 142.6 (C); APCI-MS m/z (rel intensity) 223
([MþHꢁH2O]þ, 23), 193 (36), 178 (65), 161 (100); HRMS
[MþHꢁH2O]þ for C11H12Br: 223.0117, found 223.0124. These data
are in agreement with those reported in the literature.7
1f
3f
3h
3i
O
O
O
NC
Br
Br
NC
Br
1h
O
Br
4.2.1.2. 1-Bromo-2-p-tolylpent-4-en-2-ol (2b). Following the
general procedure, the title compound was obtained (242 mg, 95%).
An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.50; 1H NMR (300 MHz, CDCl3)
1i
OMe O
Br
OMe O
OMe
d
2.34 (s, 3H), 2.56 (s, 1H), 2.72 (d, J¼7.2 Hz, 2H), 3.72 (d, J¼11.1 Hz,
1H), 3.76 (d, J¼11.1 Hz, 1H), 5.07e5.29 (m, 2H), 5.52e5.66 (m, 1H),
1k
3k
7.18 (d, J¼8.1 Hz, 2H), 7.30 (d, J¼8.1 Hz, 2H); 13C NMR (75 MHz,
OMe
CDCl3)
d 20.9 (CH3), 44.6 (CH2), 44.8 (CH2), 74.5 (C), 119.4 (CH2),
O
O
125.2 (CHꢀ2), 129.0 (CHꢀ2), 132.6 (CH), 137.0 (C), 139.7 (C); APCI-
MS m/z (rel intensity) 237 ([MþHꢁH2O]þ, 50), 192 (20), 175 (100),
159 (57); HRMS [MþHꢁH2O]þ for C12H14Br: 237.0273, found
237.0281. These data are in agreement with those reported in the
literature.7
Br
10
67
1l
3l
O2N
O2N
a
The isolated yield was determined from phenacyl bromide 1. Labile epoxides 3b
and 3c would undergo rearrangement reaction during chromatography process to
form aldehydes.
4.2.1.3. 1-Bromo-2-(4-methoxyphenyl)pent-4-en-2-ol
(2c). Following the general procedure, the title compound was
obtained (198 mg, 73%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.35;
1H NMR (300 MHz, CDCl3)
d
2.51 (s, 1H), 2.70 (dd, J¼7.2, 0.9 Hz, 2H),
3. Conclusion
3.70 (d, J¼10.5 Hz, 1H), 3.72 (d, J¼10.5 Hz, 1H), 3.79 (s, 3H),
5.05e5.14 (m, 2H), 5.50e5.64 (m,1H), 6.87 (d, J¼8.1 Hz, 2H), 7.32 (d,
The investigation described above has led to the development of
a method for the synthesis of homoallylic bromohydrins in an
aqueous medium. In addition, we showed that the homoallylic
bromohydrins can be directly converted to allylic epoxides and
a 3-allylbenzofuran.
J¼8.1 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d 44.7 (CH2), 44.8 (CH2),
55.2 (CH3), 74.4 (C), 113.6 (CHꢀ2), 119.5 (CH2), 126.6 (CHꢀ2), 132.6
(CH), 134.7 (C), 158.8 (C); APCI-MS m/z (rel intensity) 255 (87), 253
([MþHꢁH2O]þ, 100), 208 (12), 191 (24); HRMS [MþHꢁH2O]þ for

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M.-H. Lin et al. / Tetrahedron 69 (2013) 8263e8268
C12H14BrO: 253.0223, found 253.0230. These data are in agreement
with those reported in the literature.7
4.2.1.9. 1-Bromo-2-(3-bromophenyl)pent-4-en-2-ol
(2i). Following the general procedure, the title compound was
obtained (307 mg, 96%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.50;
4. 2.1. 4. 1-Bromo-2-(4-bromophenyl)pent-4-en-2-ol
(2d). Following the general procedure, the title compound was
obtained (275 mg, 86%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.45;
1H NMR (300 MHz, CDCl3)
d
2.57 (s, 1H), 2.68 (d, J¼7.2 Hz, 2H), 3.71
(s, 2H), 5.08e5.14 (m, 2H), 5.49e5.63 (m, 1H), 7.19e7.32 (m, 2H),
7.39e7.42 (m, 1H), 7.58 (t, J¼1.8 Hz, 1H); 13C NMR (75 MHz, CDCl3)
1H NMR (300 MHz, CDCl3)
d
2.58 (s, 1H), 2.68 (dd, J¼7.2, 0.9 Hz, 2H),
d 43.9 (CH2), 44.8 (CH2), 74.4 (C), 120.0 (CH2), 122.7 (C), 124.0
3.68 (d, J¼10.8 Hz, 1H), 3.72 (d, J¼10.8 Hz, 1H), 5.06e5.12 (m, 2H),
(CH), 128.7 (CH), 129.8 (CH), 130.6 (CH), 131.9 (CH), 145.2 (C);
IR (neat) 3543, 3080, 1562 cmꢁ1; APCI-MS m/z (rel intensity)
301 ([MþHꢁH2O]þ, 5), 223 (93), 221 (100), 157 (38); HRMS
[MþHꢁH2O]þ for C11H11Br2: 300.9222, found 300.9223.
5.48e5.62 (m, 1H), 7.27 (d, J¼8.1 Hz, 2H), 7.47 (d, J¼8.1 Hz, 2H); 13
C
NMR (75 MHz, CDCl3) d 44.0 (CH2), 44.8 (CH2), 74.5 (C), 120.0 (CH2),
121.5 (C), 127.3 (CHꢀ2), 131.4 (CHꢀ2), 132.0 (CH), 141.8 (C); IR (neat)
3536, 2927, 1493 cmꢁ1; APCI-MS m/z (rel intensity) 305 (47), 303
(100), 301 ([MþHꢁH2O]þ, 52); HRMS [MþHꢁH2O]þ for C11H11Br2:
300.9222, found 300.9233.
4.2.1.10. 3-(1-Bromo-2-hydroxypent-4-en-2-yl)phenol
(2j). Following the general procedure, the title compound was
obtained (208 mg, 81%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.30;
4.2.1.5. 1-Bromo-2-(4-chlorophenyl)pent-4-en-2-ol
(2e). Following the general procedure, the title compound was
obtained (265 mg, 96%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.42;
1H NMR (300 MHz, CDCl3)
d
2.64 (s, 1H), 2.69 (d, J¼7.2 Hz, 2H), 3.71
(s, 2H), 5.06e5.14 (m, 2H), 5.50e5.61 (m, 2H), 6.74 (d, J¼8.1 Hz, 1H),
6.88e6.95 (m, 2H), 7.20 (d, J¼8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3)
1H NMR (300 MHz, CDCl3)
d
2.57 (s, 1H), 2.68 (d, J¼7.8 Hz, 2H), 3.68
d 44.2 (CH2), 44.8 (CH2), 74.7 (C), 112.7 (CH), 114.5 (CH), 117.6 (CH),
(d, J¼10.5 Hz, 1H), 3.72 (d, J¼10.5 Hz, 1H), 5.07e5.13 (m, 2H),
119.8 (CH2), 129.6 (CH), 132.3 (CH), 144.6 (C), 155.7 (C); IR (neat)
5.48e5.62 (m, 1H), 7.29 (d, J¼8.1 Hz, 2H), 7.34 (d, J¼8.1 Hz, 2H); 13
C
3527, 3323, 1592 cmꢁ1
; APCI-MS m/z (rel intensity) 241
NMR (75 MHz, CDCl3)
d
44.1 (CH2), 44.8 (CH2), 74.5 (C), 120.0 (CH2),
([MþHꢁH2Oþ2]þ, 20), 239 ([MþHꢁH2O]þ, 22), 177 (100), 159 (57);
126.9 (CHꢀ2), 128.4 (CHꢀ2), 132.0 (CH), 133.3 (C), 141.3 (C); APCI-
MS m/z (rel intensity) 261 (8), 259 (32), 257 ([MþHꢁH2O]þ, 27),
177 (100); HRMS [MþHꢁH2O]þ for C11H11BrCl: 256.9727, found
256.9735. These data are in agreement with those reported in the
literature.4
HRMS [MþHꢁH2O]þ for C11H12BrO: 239.0066, found 239.0072.
4.2.1.11. 1-Bromo-2-(2,5-dimethoxyphenyl)pent-4-en-2-ol
(2k). Following the general procedure, the title compound was
obtained (298 mg, 99%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.35;
1H NMR (300 MHz, CDCl3)
d
2.67 (dd, J¼13.8, 7.8 Hz, 1H), 2.99 (dd,
4.2.1.6. 1-Bromo-2-(naphthalen-2-yl)pent-4-en-2-ol
(2f). Following the general procedure, the title compound was
obtained (256 mg, 88%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.42;
J¼13.8, 6.3 Hz, 1H), 3.32 (s, 1H), 3.75 (s, 3H), 3.79 (s, 3H), 3.83 (d,
J¼10.2 Hz, 1H), 4.03 (d, J¼10.2 Hz, 1H), 5.00e5.11 (m, 2H),
5.55e5.68 (m, 1H), 6.74e6.82 (m, 2H), 7.06 (d, J¼2.7 Hz, 1H); 13C
1H NMR (300 MHz, CDCl3)
d
2.70 (s, 1H), 2.80 (dd, J¼7.8, 0.9 Hz,
NMR (75 MHz, CDCl3) d 42.0 (CH2), 42.8 (CH2), 55.6 (CH3), 55.7
2H), 3.83 (d, J¼10.8 Hz, 1H), 3.86 (d, J¼10.8 Hz, 1H), 5.05e5.17 (m,
(CH3), 74.9 (C), 111.9 (CH), 112.8 (CH), 114.7 (CH), 118.5 (CH2), 131.4
2H), 5.52e5.66 (m, 1H), 7.45e7.51 (m, 3H), 7.81e7.93 (m, 4H); 13C
(C), 133.4 (CH), 150.0 (C), 153.3 (C); IR (neat) 3512, 2941, 1501 cmꢁ1
;
NMR (75 MHz, CDCl3)
d
44.4 (CH2), 44.8 (CH2), 74.9 (C), 119.7
APCI-MS m/z (rel intensity) 285 ([MþHꢁH2Oþ2]þ, 57), 283
(CH2), 123.2 (CH), 124.7 (CH), 126.1 (CH), 126.2 (CH), 127.5 (CH),
128.1 (CH), 128.2 (CH), 132.4 (CH), 132.5 (C), 133.0 (C), 140.1 (C);
APCI-MS m/z (rel intensity) 275 (80), 273 ([MþHꢁH2O]þ, 88), 211
(100), 193 (54); HRMS [MþHꢁH2O]þ for C15H14Br: 273.0273,
found 273.0287. These data are in agreement with those reported
in the literature.4
([MþHꢁH2O]þ, 63), 221 (79), 203 (100); HRMS [MþHꢁH2O]þ for
C13H16BrO2: 283.0328, found 283.0337.
4. 2.1.12. 1-Bromo-2-(4-nitrophenyl)pent-4-en-2-ol
(2l). Following the general procedure, the title compound was
obtained (223 mg, 78%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.42;
1H NMR (300 MHz, CDCl3)
d
2.71 (d, J¼7.2 Hz, 2H), 2.76 (s, 1H), 3.75
4.2.1.7. 2-(1-Bromo-2-hydroxypent-4-en-2-yl)phenol
(2g). Following the general procedure, the title compound was
obtained (219 mg, 85%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.12;
(d, J¼10.5 Hz, 1H), 3.78 (d, J¼10.5 Hz, 1H), 5.05e5.13 (m, 2H),
5.48e5.62 (m, 1H), 7.58 (d, J¼9.6 Hz, 2H), 8.19 (d, J¼9.6 Hz, 2H); 13
C
NMR (75 MHz, CDCl3) d 43.3 (CH2), 44.9 (CH2), 74.9 (C), 120.4 (CH2),
1H NMR (300 MHz, CDCl3)
d
2.83 (dd, J¼7.8, 0.9 Hz, 2H), 3.28 (s, 1H),
123.4 (CHꢀ2), 126.6 (CHꢀ2), 131.3 (CH), 147.1 (C), 150.2 (C); APCI-
MS m/z (rel intensity) 286 ([MþH]þ, 19), 268 (37), 239 (51), 159
(100); HRMS [MþH]þ for C11H13BrNO3: 286.0073, found 286.0080.
These data are in agreement with those reported in the literature.6
3.72 (d, J¼10.8 Hz, 1H), 3.91 (d, J¼10.8 Hz, 1H), 5.14e5.21 (m, 2H),
5.60e5.74 (m, 1H), 6.80e6.88 (m, 2H), 6.99 (dd, J¼7.8, 1.5 Hz, 1H),
7.15e7.21 (m, 1H), 8.73 (s, 1H); 13C NMR (75 MHz, CDCl3)
d 42.6
(CH2), 43.1 (CH2), 77.8 (C), 118.1 (CH), 119.6 (CH), 120.4 (CH2), 124.0
(C), 126.7 (CH), 129.7 (CH), 131.8 (CH), 156.2 (C); IR (neat) 3242,
2978, 1583 cmꢁ1; APCI-MS m/z (rel intensity) 241 (41), 239
([MþHꢁH2O]þ, 45), 177 (10), 159 (100); HRMS [MþHꢁH2O]þ for
4.2.2. General procedure for indium-mediated allylation reactions of
a-bromoketones to form epoxides in one-pot. A mixture of allyl
bromide (2.0 mmol), indium powder (1.0 mmol), and -bromoke-
a
C
11H12BrO: 239.0066, found 239.0072.
tone (1.0 mmol) in THF/H2O (0.5 mL:1.5 mL) was stirred at ambient
temperature. Reaction was monitored by TLC until no starting
material was observed and normally the reaction mixture was
stirred at rt overnight. NaOH (2 N) aqueous solution (2.5 mL) was
then added to the reaction mixture and the mixture was stirred at rt
for 2 h. The reaction mixture was then extracted with Et2O
(5 mLꢀ2). The combined organic layers were washed with brine
(3 mLꢀ2), dried over MgSO4, and concentrated in a rotary evapo-
rator. The residue was purified by silica-gel chromatography using
hexanes as eluent to give the product.
4.2.1.8. 3-(1-Bromo-2-hydroxypent-4-en-2-yl)benzonitrile
(2h). Following the general procedure, the title compound was
obtained (261 mg, 98%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.20;
1H NMR (300 MHz, CDCl3)
d
2.68 (d, J¼6.9 Hz, 2H), 2.82 (s, 1H), 3.71
(s, 2H), 5.04e5.10 (m, 2H), 5.49e5.58 (m, 1H), 7.24e7.63 (m, 3H),
7.73 (s, 1H); 13C NMR (75 MHz, CDCl3)
d
43.3 (CH2), 44.6 (CH2), 74.4
(C), 112.0 (C), 118.6 (CH), 120.1 (CH2), 128.9 (CH), 129.3 (CH), 129.9
(CH), 130.9 (CH), 131.3 (CH), 144.4 (C); IR (neat) 3468, 3075,
2229 cmꢁ1; APCI-MS m/z (rel intensity) 266 ([MþH]þ, 100), 248
(27), 186 (60), 168 (67); HRMS [MþH]þ for C12H13BrNO: 266.0175,
found 266.0185.
4.2.2.1. 2-Allyl-2-phenyloxirane (3a). Following the general
procedure, the title compound was obtained (123 mg, 77%). An oil;

M.-H. Lin et al. / Tetrahedron 69 (2013) 8263e8268
8267
TLC (Et2O/hexanes (1:4)) Rf¼0.67; 1H NMR (300 MHz, CDCl3)
d
2.64
5.64e5.78 (m, 1H), 7.42 (t, J¼7.5 Hz, 1H), 7.52e7.64 (m, 3H); 13C
(dd, J¼15.0, 7.2 Hz, 1H), 2.75 (d, J¼5.4 Hz, 1H), 2.87 (dd, J¼15.0,
NMR (75 MHz, CDCl3) d 38.7 (CH2), 54.7 (CH2), 58.3 (C), 112.3 (C),
7.2 Hz, 1H), 2.99 (d, J¼5.4 Hz, 1H), 5.06e5.16 (m, 2H), 5.70e5.84 (m,
118.4 (C), 119.0 (CH2), 129.0 (CH), 129.4 (CH), 130.2 (CH), 130.9 (CH),
131.7 (CH), 141.5 (C); IR (neat) 3068, 2232, 1484 cmꢁ1; EIMS m/z (rel
intensity) 185 (Mþ, 3), 154 (15), 130 (100), 116 (39); HRMS [M]þ for
1H), 7.24e7.39 (m, 5H); 13C NMR (75 MHz, CDCl3)
d 39.4 (CH2), 54.7
(CH2), 59.2 (C), 118.3 (CH2), 125.8 (CHꢀ2), 127.4 (CH), 128.2 (CHꢀ2),
132.6 (CH), 139.9 (C). These data are in agreement with those re-
ported in the literature.8a
C12H11NO: 185.0841, found 185.0833.
4.2.2.8. 2-Allyl-2-(3-bromophenyl)oxirane (3i). Following the
4.2.2.2. 2-Allyl-2-p-tolyloxirane (3b). Following the general pro-
general procedure, the title compound was obtained (182 mg, 76%).
cedure, the title compound was obtained (132 mg, 76%). An oil; TLC
An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.75; 1H NMR (300 MHz, CDCl3)
(Et2O/hexanes(1:4))Rf¼0.70;1HNMR(300MHz,CDCl3)
d
2.32(s, 3H),
d
2.59 (dd, J¼15.0, 6.6 Hz, 1H), 2.70 (d, J¼5.1 Hz,1H), 2.85 (dd, J¼15.0,
2.62 (dd, J¼15.0, 7.5 Hz, 1H), 2.73 (d, J¼5.4 Hz, 1H), 2.87 (ddt, J¼15.0,
7.5,1.5Hz,1H), 2.97(d,J¼5.4Hz,1H), 5.04e5.14(m, 2H),5.69e5.83(m,
1H), 7.13 (d, J¼7.8 Hz, 2H), 7.25 (d, J¼7.8 Hz, 2H); 13C NMR (75 MHz,
7.5 Hz, 1H), 2.98 (d, J¼5.1 Hz, 1H), 5.07e5.15 (m, 2H), 5.66e5.79 (m,
1H), 7.15e7.39 (m, 4H); 13C NMR (75 MHz, CDCl3)
d
39.1 (CH2), 54.7
(CH2), 58.6 (C), 118.8 (CH2), 122.4 (C), 124.5 (CH), 128.9 (CH), 129.8
(CH), 130.5 (CH), 132.1 (CH), 142.3 (C); IR (neat) 3086, 2912,
1571 cmꢁ1; EIMS m/z (rel intensity) 239 (Mþ, 5), 183 (100), 169 (28),
128 (83); HRMS [M]þ for C11H11BrO: 237.9993, found 237.9988.
CDCl3) d 21.0 (CH3), 39.5 (CH2), 54.8 (CH2), 59.1 (C), 118.3 (CH2), 125.8
(CHꢀ2),128.9(CHꢀ2),132.8(CH),136.9(C),137.1 (C). These data arein
agreement with those reported in the literature.8a
4.2.2.3. 2-Allyl-2-(4-methoxyphenyl)oxirane (3c). Following the
general procedure, the title compound was obtained (143 mg, 75%).
An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.50; 1H NMR (300 MHz, CDCl3)
4.2.2.9. 2-Allyl-2-(2,5-dimethoxyphenyl)oxirane (3k). Following
the general procedure, the title compound was obtained (161 mg,
73%). An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.44; 1H NMR (300 MHz,
d
2.62 (dd, J¼14.7, 7.5 Hz, 1H), 2.73 (d, J¼5.4 Hz, 1H), 2.83 (ddt,
CDCl3)
d
2.50 (dd, J¼14.7, 7.5 Hz,1H), 2.69 (d, J¼5.1 Hz,1H), 2.84 (dd,
J¼14.7, 7.5, 1.2 Hz, 1H), 2.96 (d, J¼5.4 Hz, 1H), 3.76 (s, 3H), 5.05e5.15
(m, 2H), 5.70e5.84 (m, 1H), 6.85 (d, J¼8.7 Hz, 2H), 7.29 (d, J¼8.7 Hz,
J¼14.7, 7.5 Hz, 1H), 2.94 (d, J¼5.1 Hz, 1H), 3.71 (s, 3H), 3.77 (s, 3H),
4.97e5.04 (m, 2H), 5.62e5.76 (m, 1H), 6.74 (s, 2H), 6.89 (m, 1H); 13
NMR (75 MHz, CDCl3) 39.5 (CH2), 53.0 (CH2), 55.4 (CH3), 55.5
(CH3), 58.6 (C), 111.1 (CH), 113.3 (CH), 113.6 (CH), 117.7 (CH2), 129.4
C
2H); 13C NMR (75 MHz, CDCl3)
d
39.5 (CH2), 54.6 (CH2), 55.0 (CH3),
d
58.8 (C), 113.4 (CHꢀ2), 118.1 (CH2), 127.0 (CHꢀ2), 131.8 (C), 132.8
(CH), 158.8 (C); IR (neat) 3048, 2938, 1518 cmꢁ1; EIMS m/z (rel in-
tensity) 190 (Mþ, 15), 161 (56), 135 (100), 121 (38); HRMS [M]þ for
(C), 132.8 (CH), 150.8 (C), 153.1 (C); IR (neat) 2940, 2833, 1500 cmꢁ1
;
EIMS m/z (rel intensity) 220 (Mþ, 43), 191 (24), 165 (100), 121 (41);
C
12H14O2: 190.0994, found 190.0991.
HRMS [M]þ for C13H16O3: 220.1099, found 220.1093.
4.2.2.4. 2-Allyl-2-(4-bromophenyl)oxirane (3d). Following the
4.2.2.10. 2-Allyl-2-(4-nitrophenyl)oxirane (3l). Following the
general procedure, the title compound was obtained (137 mg, 67%).
An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.37; 1H NMR (300 MHz, CDCl3)
general procedure, the title compound was obtained (189 mg, 79%).
An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.62; 1H NMR (300 MHz, CDCl3)
d
2.57 (dd, J¼15.0, 7.2 Hz, 1H), 2.66 (d, J¼5.4 Hz, 1H), 2.83 (dd,
d
2.62 (dd, J¼15.0, 7.2 Hz, 1H), 2.72 (d, J¼5.1 Hz, 1H), 2.93 (dd,
J¼15.0, 6.6 Hz, 1H), 2.95 (d, J¼5.4 Hz, 1H), 5.05e5.13 (m, 2H),
J¼15.0, 7.2 Hz, 1H), 3.05 (d, J¼5.1 Hz, 1H), 5.08e5.15 (m, 2H),
5.65e5.79 (m, 1H), 7.21 (d, J¼8.4 Hz, 2H), 7.41 (d, J¼8.4 Hz, 2H); 13
C
5.65e5.79 (m, 1H), 7.51 (d, J¼7.2 Hz, 2H), 8.16 (d, J¼7.2 Hz, 2H); 13
C
NMR (75 MHz, CDCl3)
d
38.9 (CH2), 54.5 (CH2), 58.5 (C), 118.5 (CH2),
NMR (75 MHz, CDCl3) d 38.7 (CH2), 54.9 (CH2), 58.6 (C), 119.0 (CH2),
121.2 (C), 127.5 (CHꢀ2), 131.1 (CHꢀ2), 132.1 (CH), 138.9 (C). These
123.3 (CHꢀ2), 126.7 (CHꢀ2), 131.6 (CH), 147.0 (C), 147.3 (C); EIMS m/
z (rel intensity) 205 (Mþ, 2),164 (9), 150 (100), 128 (52); HRMS [M]þ
for C11H11NO3: 205.0739, found 205.0743. These data are in
agreement with those reported in the literature.14
data are in agreement with those reported in the literature.8a
4.2.2.5. 2-Allyl-2-(4-chlorophenyl)oxirane (3e). Following the
general procedure, the title compound was obtained (158 mg, 81%).
An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.67; 1H NMR (300 MHz, CDCl3)
4.3. 3-Allylbenzofuran (3g)
d
2.59 (dd, J¼15.0, 7.2 Hz, 1H), 2.69 (d, J¼5.4 Hz, 1H), 2.84 (ddt,
J¼15.0, 7.2, 1.2 Hz, 1H), 2.98 (d, J¼5.4 Hz, 1H), 5.05e5.13 (m, 2H),
To a solution of 2g (257 mg, 1 mmol) in acetone (4 mL) was
added K2CO3 (414 mg, 3 mmol) at rt and the suspension was stirred
at rt for 3 h. CH2Cl2 (5 mL) and 10% aq NH4Cl (5 mL) were added. The
mixture was transferred to a separatory funnel and the aqueous
layer was extracted with CH2Cl2 (5 mLꢀ2). The organic layers were
combined, dried over MgSO4, and concentrated in a rotary evapo-
rator. The residue was dissolved in benzene (3.5 mL) and TsOH/H2O
(6 mg, 0.03 mmol) was added. The mixture was heated at reflux for
1 h and then the mixture was cooled to rt. Et2O (5 mL) and 10% aq
NaHCO3 (5 mL) were added. The mixture was transferred to a sep-
aratory funnel and the aqueous layer was extracted with Et2O
(5 mLꢀ2). The organic layers were combined, dried over MgSO4,
and concentrated in a rotary evaporator. The residue was purified
by silica-gel chromatography using Et2O/hexanes (1:10) as eluent
to give the product 3g (130 mg, 82%). An oil; TLC (hexanes) Rf¼0.5;
5.66e5.80 (m, 1H), 7.28 (br s, 4H); 13C NMR (75 MHz, CDCl3)
d
39.2
(CH2), 54.8 (CH2), 58.7 (C), 118.6 (CH2), 127.3 (CHꢀ2), 128.4 (CHꢀ2),
132.3 (CH), 133.2 (C), 138.4 (C). These data are in agreement with
those reported in the literature.8a
4.2.2.6. 2-Allyl-2-(naphthalen-2-yl)oxirane (3f). Following the
general procedure, the title compound was obtained (162 mg, 77%).
An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.57; 1H NMR (300 MHz, CDCl3)
d
2.73 (dd, J¼15.0, 7.2 Hz, 1H), 2.84 (d, J¼5.4 Hz, 1H), 3.00 (ddt,
J¼15.0, 7.2, 1.2 Hz, 1H), 3.07 (d, J¼5.4 Hz, 1H), 5.06e5.19 (m, 2H),
5.74e5.88 (m, 1H), 7.43e7.50 (m, 3H), 7.80e7.85 (m, 4H); 13C NMR
(75 MHz, CDCl3) d 39.2 (CH2), 54.6 (CH2), 59.3 (C), 118.3 (CH2), 123.5
(CH), 124.8 (CH), 125.8 (CH), 126.0 (CH), 127.4 (CH), 127.7 (CH), 127.8
(CH), 132.5 (CH), 132.5 (C), 132.9 (C), 137.2 (C). These data are in
agreement with those reported in the literature.8a
1H NMR (300 MHz, CDCl3)
2H), 6.00e6.13 (m, 1H), 7.24e7.35 (m, 2H), 7.44e7.60 (m, 3H); 13C
NMR (75 MHz, CDCl3) 28.0 (CH2), 111.3 (CH), 116.3 (CH2), 118.3 (C),
d
3.46 (d, J¼7.8 Hz, 2H), 5.14e5.27 (m,
4.2.2.7. 3-(2-Allyloxiran-2-yl)benzonitrile (3h). Following the
general procedure, the title compound was obtained (156 mg, 84%).
An oil; TLC (Et2O/hexanes (1:4)) Rf¼0.35; 1H NMR (300 MHz, CDCl3)
d
119.7 (CH), 122.2 (CH), 124.1 (CH), 128.0 (C), 135.3 (CH), 141.5 (CH),
155.4 (C); EIMS m/z (rel intensity) 158 (Mþ, 100), 131 (60), 113 (16),
77 (15); HRMS [M]þ for C11H10O: 158.0732, found 158.0730. These
data are in agreement with those reported in the literature.13
d
2.60 (dd, J¼15.0, 6.6 Hz, 1H), 2.70 (d, J¼5.1 Hz, 1H), 2.87 (dd,
J¼15.0, 6.6 Hz, 1H), 3.02 (d, J¼5.1 Hz, 1H), 5.07e5.14 (m, 2H),

8268
M.-H. Lin et al. / Tetrahedron 69 (2013) 8263e8268
A. Tetrahedron Lett. 1998, 39, 6281; (d) Wender, P. A.; Sieburth, S. M.; Petraitis, J.
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Financial support from the National Science Council of the
Republic of China, Taiwan (NSC102-2113-M-018-004-MY2) is
gratefully acknowledged.
6. Yadav, J. S.; Reddy, B. V. S.; Biswas, S. K.; Sengupta, S.; Vishnumurthy, P. Tetra-
hedron Lett. 2008, 49, 1034.
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Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.07.012.
9. (a) Lin, M.-H.; Hung, S.-F.; Lin, L.-Z.; Tsai, W.-S.; Chuang, T.-H. Org. Lett. 2011, 13,
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