Synthesis of β-haloketones by β-addition reactions of α,β-unsaturated ketones with BX3 (X = Br, Cl) as halide source

Article abstract of DOI:10.1002/jccs.201300394

A series of β-bromoketones and β-chloroketones were synthesized by the addition reactions of α,β-unsaturated ketones under BX ₃ (X = Br, Cl) and ethylene glycol reaction system. The α,β-unsaturated ester also was successfully converted to its corresponding β-bromoester under the reaction condition. A series of β-bromoketones and β-chloroketones were synthesized by the addition reactions of α,β-unsaturated ketones under BX₃ (X=Br, Cl) and ethylene glycol reaction system. Copyright

Full text of DOI:10.1002/jccs.201300394

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Synthesis of b-Haloketones by b-Addition Reactions of a,b-Unsaturated Ketones with
BX (X = Br, Cl) as Halide Source
3
Adam Shih-Yuan Lee,* Shu-Huei Wang and Yu-Ting Chang
Department of Chemistry, Tamkang University, New Taipei City, Taiwan 251
(Received: Aug. 1, 2013; Accepted: Sept. 25, 2013; Published Online: Dec. 9, 2013; DOI: 10.1002/jccs.201300394)
A series of b-bromoketones and b-chloroketones were synthesized by the addition reactions of a,b-unsat-
3
urated ketones under BX (X = Br, Cl) and ethylene glycol reaction system. The a,b-unsaturated ester also
was successfully converted to its corresponding b-bromoester under the reaction condition.
3
Keywords: b-Bromoketone; b-Chloroketone; a,b-Unsaturated ketone; b-Addition reaction; BBr ;
3
BCl .
INTRODUCTION
A b-substituted carbonyl compound is potentially bi-
ological active molecule and the important synthetic inter-
1
-4
mediate in organic synthesis. Synthetic methodologies
for synthesis of b-substituted carbonyl compounds are typ-
ically produced by the addition reactions such as Aldol-
5
,6
7,8
type reaction, organocopper addition reaction and Mi-
9
,10
chael addition reaction. Conjugate addition of organo-
metallic reagent to a,b-unsaturated carbonyl compound is
the commonly used method for specific introduction of a
3
with Lewis acid AlCl which serves as chloride source by
introducing promotion agents.
1
1
substituent to the b-position of carbonyl functionality.
RESULTS AND DISCUSSIONS
Recently, our laboratory reported the synthesis of b-meth-
oxyketones, b-aminoketones B, and b-amidoketones by a
Lewis acids promoted b-addition reactions of a,b-unsatu-
The first test of our approach was examined by reac-
tion of 1-phenyl-pent-3-en-2-one A and Lewis acid AlCl
with 2 drops of ammonia solution as promoting reagent in
CH Cl and the reaction mixture was stirred at room tem-
3
1
2,13
rated ketones under mild reaction conditions.
taminated b-chloroketone C was usually observed and
characterized when Lewis acids such as AlCl and ZrCl
A con-
2
2
perature (Scheme 2). The reaction mixture was stirred at
room temperature for 42 hours and the expected product
b-chloroketone C (47%) was obtained with recovery of
1-phenyl-pent-3-en-2-one A (18%).
3
4
were used for promotion of b-additional reaction of a,b-
unsaturated ketone (Scheme 1). The formation of b-chloro-
ketone as side product also was observed and reported by
The higher yield of b-chloroketone C (84%) was
achieved when promoter ethylene glycol (3 equivalents to
1
4,15
other addition reaction conditions.
1
Some synthetic ap-
6-22
plications
of b-halocarbonyl compounds such as b-bro-
AlCl
observed. We think that BCl
nucleophile easier than AlCl when ethylene glycol was in-
3
) was used and much shorter reaction time also was
moketone and b-bromoester have been reported in the liter-
atures. To our knowledge, only a few direct preparation of
b-chlorocarbonyl compounds which by reaction of a,b-un-
3
may release chloride as
3
troduced as promoter under the reaction condition. There-
fore, a reaction mixture of 1-phenyl-pent-3-en-2-one A
saturated ketone with excess Me
3
SiCl/H
tion and b-additional reaction of b-methylsulfonylester
with AlCl have been reported in the literatures. The diffi-
cult preparations of b-halocarbonyl compounds restrict
2
O reaction condi-
2
3
24
(1.0 equivalent), BCl
3
(1.0 equivalent) and ethylene glycol
Cl was investigated and stirred at 0
(1.0 equivalent) in CH
2
2
3
o
C. The experimental results showed that b-chloroketone C
was afforded with 85% and the reaction time was shortened
from 5 days to half an hour. The formation yield was dra-
2
3-26
their further synthetic applications.
Thus, we expected
that the preparation of b-chloroketone may be achieved by
the Michael addition reaction of a,b-unsaturated ketone
matically improved to 96% when 1.2 equivalents of BCl
3
*
Corresponding author. Tel: +8862-2621-5656#2543; Fax: +8862-2622-3830; E-mail: adamlee@mail.tku.edu.tw
364
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J. Chin. Chem. Soc. 2014, 61, 364-368

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Synthesis of b-Haloketones from a,b-Unsaturated Ketones and BX
3
and HOCH
system. Thus, we further investigated this method for the
preparation of b-bromoketone by reaction of BBr as bro-
2 2
CH OH to substrate were used as the reaction
3
mide source with 1-phenyl-pent-3-en-2-one under the re-
action condition. As shown in Scheme 2, b-bromoketone
was also obtained with high yield (96%) under the reaction
condition. Herewith, we wish to report the synthesis of
b-haloketones by the b-additional reactions of a,b-unsatu-
rated ketones with BX
tion system.
3 2 2
(X = Br, Cl)/HOCH CH OH reac-
To understand and expand the scope for synthesis of
b-haloketones by this reaction system BX (X = Br, Cl)/
HOCH CH OH, a series of a,b-unsaturated ketones was
3
2
2
investigated and the results are shown in Table 1. The ex-
perimental results showed that alkyl and aryl a,b-unsatu-
rated ketones were successfully converted to their corre-
sponding b-bromoketones and b-chloroketones under the
reaction condition.
28
agents. The b-bromoketone C was introduced into AIBN
(
azobis(isobutyronitrile)) and Bu SnH (tributyltin hydride)
3
in benzene and the reaction mixture was refluxed for 11
hours (Scheme 4).
A few previous reports showed that b-bromoester
was used for synthesis of some synthetic intermediates and
1
6-21
biologically active compounds.
invetigated the reaction of a,b-unsaturated ester under this
reaction condition. BBr was added dropwise to a solution
2
of methyl acrylate and ethylene glycol in CH Cl at 0 C
Therefore, we further
3
o
2
and then the reaction mixture was stirred at room tempera-
ture for 24 hours. As shown in Scheme 3, a 96% yield of
b-bromoester was obtained with longer reaction time
which compared to a,b-unsaturated ketone under this reac-
tion condition.
The experimental results showed that b-bromoketone
undergo dehalogenation reaction and which was converted
to its corresponding hydrogenated product D (83%) with
small amount of contaminated a,b-unsaturated ketone A
(5%). b-Chloroketone also underwent this dehalogenation
To understand and expand the synthetic applications
of b-haloketones, we further investigated the reduction re-
3
action of b-bromoketone by using AIBN/Bu SnH reducing
J. Chin. Chem. Soc. 2014, 61, 364-368
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365

Article
Lee et al.
reaction and a lower yield of product D (64%) was obtained
with small amount of 1-phenyl-pent-3-en-2-one A (4%).
This reaction scheme may provide an alternative method
for hydrogenation reaction of a,b-unsaturated ketone to
hydrogenated ketone.
(3H, H
1.66 (3H, H
J = 17.0, 6.0), 3.04 (1H, H
8
, t, J = 7.4), 1.20-1.32 (2H, H
, d, J = 6.6), 2.37 (2H, H
, dd, J = 17.0, 7.7), 4.27 (1H, H
7
, m), 1.46-1.56 (2H, H
6
, m),
1
5
, t, J = 7.4), 2.80 (1H, H
3
, dd,
3
2
, ddq, J
1
= 7.7, 6.0, 6.); C-NMR: d 13.6, 22.1, 25.4, 26.1, 43.4, 53.0,
3
3
3
207.2; IR: (neat) 2961 (sp -CH, w), 2934 (sp -CH, w), 1716
(C=O, s), 1379 (m), 1132 (m).
As a conclusion, we demonstrate here a simple and an
efficient method for the synthesis of b-bromoketones, b-
3-Chloro-1-cyclopropylbutan-1-one (Table 1, entry 2).
1
chloroketones and b-bromoesters under BX /HOCH
3
CH OH
2 2
H-NMR: d 0.88-0.95 (2H, m), 1.05-1.10 (2H, m), 1.55 (3H, H
, dd, J = 16.8, 7.3),
, dd, J = 16.8, 6.3), 4.48 (1H, H , ddq, J = 7.3, 6.6,
6.3); C-NMR: d 10.8, 20.9, 25.0, 52.2, 52.9, 206.9; IR: (neat)
4
,
reaction conditions.
d, J = 6.6), 1.88-1.96 (1H, m), 2.88 (1H, H
2
3
.10 (1H, H
2
3
1
3
EXPERIMENTAL
3
2982 (sp -CH, w), 2931 (sp -CH, w), 1698 (C=O, m), 1388 (m),
3
General. All reagents were purchased from Aldrich and
Riedel-deHaen and all were used directly without further purifi-
cation. All experiments were carried out under a nitrogen atmo-
sphere which was dried primarily by passing through a column of
1061 (m), 618 (C-Cl, m).
3-Bromo-1-cyclopropylbutan-1-one (Table 1, entry 2).
1
H-NMR: d 1.65 (3H, H
4
, d, J = 6.6), 2.01-2.10 (2H, m), 2.54 (2H,
, dd, J = 17.0, 5.6), 3.04 (1H, H , dd, J =
17.0, 8.1), 3.37 (2H, t, J = 6.6), 4.42 (1H, H , ddq, J = 8.1, 5.6,
6.6); C-NMR: d 25.9, 26.1, 32.9, 41.1, 42.8, 53.0, 205.5; IR:
potassium hydroxide (KOH) layered with calcium sulfate (CaSO
4
).
d, J = 7.0), 2.82 (1H, H
2
2
Thin-layer chromatography (TLC) analysis was performed on a
plastic plate (or aluminum sheet) precoated with silica gel
3
1
3
3
(neat) 2964 (sp -CH, w), 2922 (sp -CH, w), 1714 (C=O, s), 1375
3
(
Merck, 5554 Silica gel 60F254). Column chromatography was
performed using silica gel (Merck 230-400 mesh) and ethyl ace-
1
tate/hexane mixture as the eluent. The H NMR (proton nuclear
(m), 1241 (m).
1
3-Chloro-1-phenylbutan-1-one (Table 1, entry 3). H-
magnetic resonance) spectra were recorded at 300 MHz (Bruker-
NMR: d 1.62 (3H, H
4
, d, J = 6.6), 3.24 (1H, H
2
3
, dd, J = 17.0, 6.6),
, ddq, J = 6.6, 6.6,
AC300P) with deuteriochloroform (CDCl
3
, Aldrich 99.8 atom%
3.57 (1H, H , dd, J = 17.0, 6.6), 4.67 (1H, H
2
1
D) as the solvent and the internal standard. The C NMR (carbon
3
6.6), 7.44-7.49 (2H, m), 7.55-7.60 (1H, m), 7.93-7.96 (1H, m);
1
3
nuclear magnetic resonance) spectra were recorded at 75.5 MHz
C-NMR: d 25.2, 48.5, 52.6, 128.0, 128.6, 133.4, 136.6, 196.5;
HRMS: m/z 182.0492 (calcd. for C10 11ClO, 182.0498); MS: m/z
(
Bruker-AC300P) with CDCl
3
as the solvent and the internal stan-
H
dard. Mass spectra (MS) were recorded on JOEL SX-102A and
VG 70-250S spectrophotometers and are reported in m/z units for
the most abundant peaks. Infrared spectra (IR) were recorded on a
Bruker Tensor 37 as a liquid film (neat).
186 (6, M+4), 184 (3, M+2), 182 (6, M), 165 (1), 147 (15), 130
(8), 115 (8), 106 (7), 105 (base), 91 (6), 77 (43); IR: (neat) 3061
2
(sp -CH, w), 2982 (sp -CH, w), 2929 (sp -CH, w), 1683 (C=O, s),
3
3
1448 (m), 1217 (m), 753 (s), 688 (s), 616 (C-Cl, m).
1
3-Bromo-1-phenylbutan-1-one (Table 1, entry 3). H-
A representative procedure for synthesis of b-bromoketone
or b-chloroketone is as follows: BX
3
(X = Br, Cl) (1.2 mmol) was
NMR: d 1.81 (3H, H
4
, d, J = 6.7), 3.38 (1H, H
2
3
, dd, J = 17.3, 6.7),
, ddq, J = 6.9, 6.7,
added dropwise to a solution of a,b-unsaturated ketone (1.0
o
(5 mL) at 0 C.
3.71 (1H, H , dd, J = 17.3, 6.9), 4.69 (1H, H
2
mmol) and ethylene glycol (1.2 mmol) in CH
2
Cl
2
6.7), 7.44-7.49 (2H, m), 7.55-7.60 (1H, m), 7.93-7.96 (1H, m);
13
C-NMR: d 26.4, 43.3, 49.3, 128.0, 128.6, 133.4, 136.4, 196.5;
2
IR: (neat) 3061 (sp -CH, w), 2979 (sp -CH, w), 2922 (sp -CH, w),
o
The reaction mixture was stirred at 0 C for 30 minutes and dis-
tilled water (10 mL) was added slowly and then the reaction mix-
ture was extracted with ether (10 mL ´3). The combined organic
3
3
1682 (C=O, m), 1448 (m), 1218 (m), 759 (m).
layer was washed with brine (20 mL), dried with MgSO
4
, filtered,
3-Chloro-1-(4-methoxyphenyl)butan-1-one (Table 1,
1
and the organic solvent was removed under reduced pressure.
1
-Chlorooctan-4-one (Table 1, Entry 1). H-NMR: d 0.85
entry 4). H-NMR: d 1.61 (3H, H
4
, d, J = 6.6), 3.18 (1H, H
, dd, J = 16.8, 6.7), 3.86 (3H, OMe, s),
3
, ddq, J = 6.7, 6.6, 6.6), 6.94 (2H, d, J = 9.0), 7.93
2
, dd, J
2
= 16.8, 6.6), 3.52 (1H, H
4.65 (1H, H
(2H, d, J = 9.0); C-NMR: d 25.3, 48.2, 53.0, 55.5, 113.8, 130.0,
2
130.4, 163.8, 195.0; HRMS: m/z 212.0602 (calcd. for C11H13ClO ,
2
(
3H, H
8
, t, J = 7.3), 1.20-1.30 (2H, H
.48 (3H, H , d, J = 6.6), 2.38 (2H, H
, dd, J = 16.8, 7.7), 4.40 (1H, H
7
, m), 1.46-1.56 (2H, H
6
, m),
1
3
1
1
5
, t, J = 7.4), 2.66 (1H, H
3
, dd,
J = 16.8, 5.8), 2.90 (1H, H
3
2
, ddq, J
1
7.7, 7.4, 5.8); C-NMR: d 13.7, 22.2, 25.1, 25.5, 43.2, 52.4,
3
=
212.0604); MS: m/z 215 (11, M+3), 214 (20, M+2), 213 (31,
3
3
2
07.3); IR: (neat) 2960 (sp -CH, w), 2933 (sp -CH, w), 1715
C=O, m), 1377 (m), 1132 (m), 616 (C-Cl, m).
-Bromooctan-4-one (Table 1, entry 1). H-NMR: d 0.85
M+1), 212 (57, M), 177 (75), 134 (49), 135 (base), 107 (28); IR:
3
3
(
(neat) 2973 (sp -CH, w), 2934 (sp -CH, w), 1674 (C=O, s), 1597
(s), 1167 (s), 1023 (m), 830 (s), 596 (C-Cl, m).
1
2
366
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CHEMICAL SOCIETY
Synthesis of b-Haloketones from a,b-Unsaturated Ketones and BX
3
3
-Bromo-1-(4-methoxyphenyl)butan-1-one (Table 1,
205.0; HRMS: m/z 290.0312 (calcd. for C15H15BrO, 290.0306);
1
entry 4). H-NMR: d 1.78 (3H, H
17.0, 6.8), 3.64 (1H, H , dd, J = 17.0, 7.0), 3.84 (3H, OMe, s),
.68 (1H, H , ddq, J = 7.0, 6.8, 6.7), 6.91 (2H, d, J = 8.9), 7.91
2H, d, J = 8.9); C-NMR: d 26.4, 43.8, 48.9, 55.4, 113.8, 129.5,
4
, d, J = 6.7), 3.30 (1H, H
2
, dd, J
MS: m/z 293 (2, M+3), 292 (8, M+2), 291 (2, M+1), 290 (8, M),
=
2
210 (15), 142 (17), 141 (base), 139 (17), 115 (32), 69 (48); IR:
2
(neat) 3045 (sp -CH, w), 2987 (sp -CH, w), 2902 (sp -CH, w),
3
3
4
3
1
3
(
1714 (C=O, m), 1126 (m), 775 (s).
1
2
2
3
30.3, 163.7, 195.0; HRMS: m/z 256.0114 (calcd. for C11
H
13BrO
2
,
4-Chloro-1-(thiophen-3-yl)pentan-2-one (Table 1, entry
1
56.0099); MS: m/z 259 (10, M+3), 258 (9, M+2), 257 (10, M+1),
7). H-NMR: d 1.50 (3H, H
5
, d, J = 6.6), 2.74 (1H, H
, dd, J = 17.0, 7.6), 3.74 (2H, H
4
, ddq, J = 7.6, 6.6, 5.7), 6.95 (1H, dd, J = 4.9, 1.3), 7.11
3
, dd, J =
56 (8, M), 177 (38), 176 (26), 136 (8), 135 (base); IR: (neat)
17.0, 5.7), 2.99 (1H, H
(1H, H
3
1
, s), 4.44
2
3
006 (sp -CH, w), 2988 (sp -CH, w), 2923 (sp -CH, w), 1673
3
1
(1H, dd, J = 2.9, 1.3), 7.31 (1H, dd, J = 4.9, 2.9); C-NMR: d
3
(
C=O, m), 1597 (m), 1260 (m), 1166 (m), 764 (s).
-Chloro-1-phenyl-pentan-2-one (Table 1, entry 5). H-
NMR: d 1.48 (3H, H , d, J = 6.5), 2.74 (1H, H , dd, J = 17.0, 6.0),
.00 (1H, H , dd, J = 17.0, 7.6), 3.72 (2H, H , s), 4.45 (1H, H
ddq, J = 7.6, 6.6, 6.0), 7.19-7.38(5H, m); C-NMR: d 25.0, 50.7,
1.5, 52.3, 127.2, 128.7, 129.4, 133.4, 204.5; MS: m/z 198 (4,
M+2), 196 (12, M), 160 (8), 106 (21), 105 (71), 92 (18), 91 (base),
9 (10), 77 (52), 69 (64), 65 (28), 63 (10), 51 (6); IR: (neat) 3031
1
4
25.0, 44.9, 51.4, 52.3, 123.2, 126.1, 128.4, 133.0, 204.0; HRMS:
5
3
m/z 203.0816 (calcd. for C15H15ClO, 203.0811); MS: m/z 205
3
3
1
4
,
(M+2, 4), 204 (M+1, 8), 203 (M, 56), 191 (10), 167 (20), 161 (4),
138 (16), 128 (6), 111 (52), 107 (32), 105 (base); IR: (neat) 3104
1
3
2
(sp -CH, w), 2980 (sp -CH, w), 1715 (C=O, s), 1126 (m), 776
3
5
(C-Cl, m).
7
4-Bromo-1-(thiophen-3-yl)pentan-2-one (Table 1, entry
2
sp -CH, w), 2982 (sp -CH, w), 1715 (C=O, s), 1127 (m), 699
3
1
(
(
7). H-NMR: d 1.68 (3H, H
5
, d, J = 6.8), 2.88 (1H, H
, dd, J = 17.2, 7.6), 3.73 (2H, H
4
, ddq, J = 7.6, 6.8, 6.0), 6.95 (1H, dd, J = 4.9, 1.0), 7.10
3
, dd, J =
C-Cl, m).
17.2, 6.0), 3.13 (1H, H
(1H, H
3
1
, s), 4.35
1
-Bromo-1-phenylpentan-2-one (Table 1, entry 5). H-
4
1
(1H, dd, J = 2.9, 1.0), 7.30 (1H, dd, J = 4.9, 2.9); C-NMR: d
3
NMR: d 1.67 (3H, H
.13 (1H, H , dd, J = 17.2, 7.6), 3.71 (2H, H
ddq, J = 7.6, 6.6, 6.2), 7.20-7.38(5H, m); C-NMR: d 26.0, 42.9,
5
, d, J = 6.6), 2.88 (1H, H
3
, dd, J = 17.2, 6.2),
3
3
1
, s), 4.49 (1H, H
4
,
26.0, 42.9, 44.7, 52.1, 123.1, 126.0, 128.4, 132.9, 204.0; HRMS:
1
3
9
m/z 245.9430 (calcd. for C H11BrOS, 245.9714); MS: m/z 248
5
2
0.4, 52.1, 127.1, 128.7, 129.4, 133.3, 204.4; HRMS: m/z
40.0149 (calcd. for C11 13BrO, 240.0150); MS: m/z 243 (9,
(15, M+2), 247 (3, M+1), 246 (25, M), 245 (12), 166 (12), 151
(34), 147 (42), 131 (36), 97 (42), 69 (13), 43 (56), 28 (base); IR:
H
2
(neat) 3051 (sp -CH, w), 2962 (sp -CH, w), 2928 (sp -CH, w),
3
3
M+3), 242 (4, M+2), 241 (9, M+1), 240 (4, M), 161 (13), 149
1
713 (C=O, m), 1264 (m), 731 (s), 702 (s).
(
(
13), 123 (22), 121 (25), 92 (20), 91 (base), 90 (20), 89 (0), 65
2
55); IR: (neat) 3060 (sp -CH, w), 3029 (sp -CH, w), 2960 (sp -
2
3
3
CH, w), 2927 (sp -CH, w), 1714 (C=O, m), 1668 (m), 1285 (m),
ACKNOWLEDGMENTS
We thank the National Science Council of Taiwan
7
78 (s).
(
NSC 98-2119-M-032-002-MY3) and Tamkang Univer-
4
-Chloro-1-(naphthalen-5-yl)pentan-2-one (Table 1, en-
1
sity for financial support.
try 6). H-NMR: d 1.43 (3H, H
5
, d, J = 6.6), 2.67 (1H, H
, dd, J = 17.1, 7.6), 4.16 (2H, H
2.1, 15.9), 4.45 (1H, H , ddq, J = 7.6, 6.6, 5.7), 7.38~7.56 (4H,
3
, dd, J =
1
2
7.1, 5.7), 2.98 (1H, H
3
1
, dd, J =
REFERENCES
4
1
m), 7.81~7.90 (3H, m); C-NMR: d 25.0, 49.1, 51.1, 52.4, 123.7,
3
1. Mann, J. Nature (London) 1994, 367, 594.
2
3
4
. Panek, J. S.; Jain, N. F. J. Org. Chem. 2001, 66, 2747.
1
2
25.6, 126.0, 126.6, 128.3, 128.4, 128.8, 130.2, 132.2, 134.0,
05.1; HRMS: m/z 246.0816 (calcd. for C15 15ClO, 246.0811);
. Schreiber, S. L. Science 1991, 251, 283.
H
. Corey, E. J.; Trybulski, E. J.; Melvin, L. S., Jr.; Nicolaou, K.
C.; Secrist, J. A.; Lett, R.; Scheldarke, P. W.; Falck, J. R.;
Brunelle, D. J.; Haslanger, M. F.; Kim, S.; Yoo, S. J. Am.
Chem. Soc. 1978, 100, 4618.
MS: m/z 249 (2, M+3), 248 (6, M+2), 247 (6, M+1), 246 (18, M),
10 (1), 144 (18), 141 (base), 139 (9), 115 (22); IR: (neat) 3047
2
2
3
(
(
sp -CH, w), 2981 (sp -CH, w), 1714 (C=O, s), 1126 (m), 774
C-Cl, s).
5
6
. Mukaiyama, T.; Narasaka, K. Org. Synth. 1987, 65, 6.
. Evans, D. A. In Asymmetric Synthesis; Morrison, J. D. Ed.;
Academic Press Inc.: New York, 1984; Vol. 3, pp 1-274.
. Rossiter, B. E.; Swingle, N. M. Chem. Rev. 1992, 92, 771.
. Krause, N.; Gerold, A. Angew. Chem. Int. Ed. Engl. 1997,
4
-Bromo-1-(naphthalen-5-yl)pentan-2-one (Table 1, en-
1
try 6). H-NMR: d 1.62 (3H, H
5
, d, J = 6.6), 2.82 (1H, H
, dd, J = 17.3, 7.7), 4.15 (2H, H
2.4, 15.9), 4.49 (1H, H , ddq, J = 7.7, 6.6, 5.9), 7.39-7.57 (4H,
3
, dd, J =
7
8
1
2
7.3, 5.9), 3.13 (1H, H
3
1
, dd, J =
4
3
6, 186.
1
m), 7.82-7.90 (3H, m); C-NMR: d 26.1, 43.0, 48.8, 51.8, 123.7,
3
9
. Oare, D. A.; Heathcock, C. H. Top. Stereochem. 1989, 19,
227-407; 1991, 20, 87-170.
1
25.5, 125.9, 126.6, 128.2, 128.4, 128.8, 130.1, 132.1, 133.9,
J. Chin. Chem. Soc. 2014, 61, 364-368
© 2014 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
367

Article
Lee et al.
1
0. Yoshikoshi, A.; Miyashita, M. Acc. Chem. Res. 1985, 18,
84.
20. Ghosh, A. K.; Lee, H. Y.; Thompson, W. J.; Culberson, C.;
Holloway, M. K.; McKee, S. P.; Munson, P. M.; Duong, T. T.;
Smith, A. M.; Darke, P. L.; Zugay, J. A.; Emini, E. A.;
Schleif, W. A.; Huff, J. R.; Anderson, P. S. J. Med. Chem.
1994, 37, 1177.
2
11. Larock, R. C. Comprehensive Organic Transformations-A
nd
Guide to Functional Group Preparations, 2 ed.; John
Wiley & Sons Inc.: New York, 1999; Chapter 15, pp 1567-
1
616.
2. Lee, A. S.-Y.; Wang, S.-H.; Chang, Y.-T.; Chu, S.-F. Synlett
003, 2359.
21. Carroll, F. I.; Berrang, B. D.; Linn, C. P. J. Med. Chem. 1980,
23, 581.
1
1
1
2
22. Rieke, R. D.; Hanson, M. V.; Brown, J. D. J. Org. Chem.
1996, 61, 2726.
3. Lee, A. S.-Y.; Lin, M. C.; Lin, C. C.; Chang, Y.-T. J. Chin.
Chem. Soc. 2010, 57, 795.
23. Boudjouk, P.; Kim, B.-K.; Han, B.-H. Synth. Commun. 1996,
26, 3479.
4. Roscales, S.; Rincon, A.; Buxaderas, E.; Csaky, A. G.
Tetrahedron Lett. 2012, 53, 4721.
24. Azzena, U.; Delogu, G.; Melloni, G.; Piccolo, O. Tetrahedron
Lett. 1989, 30, 4555.
1
1
5. Bach, R. D.; Domagala, J. M. J. Org. Chem. 1984, 49, 4181.
6. Itoh, Y.; Kitaguchi, R.; Ishikawa, M.; Naito, M.; Hashimoto,
Y. Bioorg. Med. Chem. 2011, 19, 6768.
25. Ma, S.; Li, L.; Xie, H. J. Org. Chem. 1999, 64, 5325; Ma, S.;
Li, L.; Xie, H. J. Org. Chem. 1999, 64, 5325.
26. Le Roux, C.; Gaspard-Iloughmane, H.; Dubac, J. J. Org.
Chem. 1994, 59, 2238.
1
7. Napolitano, C.; Natoni, A.; Santocanale, C.; Evensen, L.;
Lorens, J. B.; Murphy, P. V. Bioorg. Med. Chem. Lett. 2011,
2
1, 1167.
8. Napolitano, C.; McArdle, P.; Murphy, P. V. J. Org. Chem.
010, 75, 7404.
9. Couladouros, E. A.; Mihou, A. P.; Bouzas, E. A. Org. Lett.
27. Li, H.; Zhang, F.-M.; Tu, Y.-Q.; Zhang, Q.-W.; Chen, Z.-M.;
Chen, Z.-H.; Li, J. Chem. Sci. 2011, 2, 1839.
28. Jonasson, C.; Ronn, M.; Backvall, J.-E. J. Org. Chem. 2000,
65, 2122.
1
1
2
2
004, 6, 977.
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J. Chin. Chem. Soc. 2014, 61, 364-368