Iodobenzene dichloride mediated sequential C-Cl bond formation: A safe, convenient and efficient method for the direct α,α-dichlorination of β-dicarbonyl compounds

Article abstract of DOI:10.1055/s-0034-1379973

Various β-keto esters, 1,3-diketones, and β-oxo amides are directly converted into their corresponding α,α-dichloro-β-keto esters, 2,2-dichloro-1,3-diketones, and α,α-dichloro-β-oxo amides, respectively, in moderate to high yields, using iodobenzene dichl

Full text of DOI:10.1055/s-0034-1379973

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 777–782
paper
777
X. Duan et al.
Paper
Synthesis
Iodobenzene Dichloride Mediated Sequential C–Cl Bond
Formation: A Safe, Convenient and Efficient Method for the Direct
α,α-Dichlorination of β-Dicarbonyl Compounds
Xiyan Duan*
Huiyun Zhou
Xinlei Tian
O
O
PhICl2 (2.2 equiv)
O
O
R1
R2
R1
R2
4 Å MS
CH2Cl2, r.t.
Cl Cl
Jianwei Liu
Junying Ma*
12 examples
up to 88% yield
R
R
1 = alkyl, aryl
2 = alkyl, aryl, OMe,OEt, NAr
School of Chemical Engineering & Pharmaceutics, Henan
University of Science and Technology, Luoyang 471003, Henan,
P. R. of China
duanxiyan@tju.edu.cn
majy379@163.com
Received: 18.10.2014
Accepted after revision: 11.12.2014
Published online: 26.01.2015
of employing heavy metals in chlorine substitution, the de-
velopment of metal-free systems for dichlorination reac-
tions are worthwhile.
DOI: 10.1055/s-0034-1379973; Art ID: ss-2014-h0628-op
path a
Abstract Various β-keto esters, 1,3-diketones, and β-oxo amides are
directly converted into their corresponding α,α-dichloro-β-keto esters,
2,2-dichloro-1,3-diketones, and α,α-dichloro-β-oxo amides, respective-
ly, in moderate to high yields, using iodobenzene dichloride in dichloro-
methane in the presence of 4 Å molecular sieves at room temperature.
This process is postulated to proceed via the iodobenzene dichloride
mediated sequential oxidative α-chlorination of the β-dicarbonyl sub-
strates.
O
O
O
O
Pd(OAc)2
N
N
H
CuCl2, CH2Cl2
H
Cl Cl
path b
O
O
O
O
NCS
Key words iodobenzene dichloride, α,α-dichlorination, β-dicarbonyl
compounds, hypervalent iodine, C–Cl bond formation
N
H
N
H
H2O, r.t.
Cl Cl
path c
O
Carbon–chlorine bond formation is a valuable and fun-
damental transformation in organic chemistry, and has
gained significant attention due to the occurrence of this
type of bond in many biological and pharmaceutical mole-
cules.1 In particular, α,α-dichloro dicarbonyl compounds
are important and valuable synthetic intermediates in or-
ganic synthesis and medicinal chemistry. For example, the
antibiotic drugs, chloramphenicol2 and fluorothiampheni-
col,3 have a wide spectrum of applications in the pharma-
ceutical and agrochemical industries. Existing methods for
the formation of α,α-dichloro dicarbonyl compounds can
be summarized as three general approaches: (1) palladi-
um(II)-catalyzed sequential C–Cl bond formation (Scheme
1, path a);4 (2) dichlorination of dicarbonyl compounds by
reaction with N-chlorosuccinimide (NCS) (Scheme 1, path
b);5 (3) reaction with aluminum chloride/lead(IV) acetate
[AlCl3/Pb(OAc)2] (Scheme 1, path c).6 However, these meth-
ods suffer from drawbacks which include the use of hazard-
ous reagents, harsh reaction conditions or long reaction
times. In view of the cost as well as environmental concerns
AlCl3
Pb(OAc)4
O
O
O
R1
R2
R1
R2
MeCN, r.t.
Cl Cl
O
path d
O
O
O
PhICl2
R1
R2
R1
R2
4 Å MS
Cl Cl
CH2Cl2, r.t.
this work
Scheme 1 General methods for the α,α-dichlorination of β-dicarbonyl
compounds
Significant advances have been made in the develop-
ment of hypervalent iodine chemistry. Due to their ready
availability and low toxicity in comparison with classic
heavy-metal oxidants, hypervalent iodine reagents have
been applied in a large number of diverse and useful chem-
ical transformations.7 Specifically, iodobenzene dichloride
(PhICl2), a hypervalent organoiodine(III) reagent of low tox-
icity, has been widely used as an oxidant as well as a halo-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 777–782

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X. Duan et al.
Paper
Synthesis
gen source in organic reactions.8 A literature study revealed
that iodobenzene dichloride has been employed for the
chlorination of alkenes, aromatic rings, allylic alcohols and
ketones.9 Herein, we report a method for the synthesis of
2,2-dichloro dicarbonyl compounds starting from β-dicar-
bonyl compounds, via direct dichlorination processes in the
presence of iodobenzene dichloride and molecular sieves in
dichloromethane at room temperature (Scheme 1, path d).
We utilized 1,3-diphenylpropane-1,3-dione (1a) as a
model 1,3-dicarbonyl compound in order to optimize the
reaction conditions. Selected data are listed in Table 1. Ini-
tially, the amount of iodobenzene dichloride was investi-
gated. Increasing the number of equivalents of iodobenzene
dichloride (from 1.2 to 2.2) resulted in complete consump-
tion of the 1,3-dicarbonyl compound 1a and α,α-dichloro
dicarbonyl compound 2a was obtained in 75% yield, a two-
fold increase compared to the original yield (Table 1, entries
1 and 2). The addition of 4 Å molecular sieves led to an in-
creased yield of 88% (Table 1, entry 3). Solvent-screening
experiments revealed that the reaction occurred in polar as
well as nonpolar solvents (Table 1, entries 3–8), but the re-
action in dichloromethane gave the best yield within a rela-
tively short period of time (Table 1, entry 3).
We next tested different additives in this system, and
observed that trifluoroacetic acid (TFA) was effective, af-
fording the desired product, 2,2-dichloro-1,3-diphenylpro-
pane-1,3-dione (2a), in 83% yield (Table 1, entry 9). When
acetic acid (AcOH) or trimethylsilyl trifluoromethanesul-
fonate (TMSOTf) were used, the desired product 2a was ob-
tained in moderate yields (Table 1, entries 10 and 11). In the
presence of sodium tert-butoxide (t-BuONa), the reaction
proceeded smoothly to afford 2a in 78% yield (Table 1, entry
12). An examination of other bases as additives revealed
that 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and potassi-
um carbonate (K2CO3) gave decreased yields of 2a (Table 1,
entries 13 and 14).
Our investigations of the reaction conditions revealed
that C–Cl bond formation took place in the absence of addi-
tives (acid or base). We assume this is due to the fact that β-
dicarbonyl compounds, especially β-diketones, exist in
solution as a mixture of keto and enol tautomers.10 1H NMR
spectroscopic analysis showed that substrates 1e and 1f (in
CDCl3) exist in the enol form (see the Supporting Informa-
tion).
Under the optimum conditions (Table 1, entry 3), vari-
ous 1,3-dicarbonyl compounds were examined to probe the
scope and generality of this method, and the results are giv-
en in Table 2. The dichlorination of the β-keto esters, meth-
yl 3-oxo-3-phenylpropanoate (1b) and ethyl 3-oxo-3-phen-
ylpropanoate (1c), gave the dichlorinated products 2b and
2c in 77% and 70% yields, respectively (Table 2, entries 2 and
3). Substrate 1d with an electron-donating group at the
Table 1 Optimization of the Reaction Conditions for the Conversion of
β-Dicarbonyl Compound 1a into α,α-Dichloro Dicarbonyl Product 2aa
PhICl2
O
O
O
O
4 Å MS
solvent
r.t.
Cl Cl
1a
2a
Entry
PhICl2
(equiv)
Additive
Solvent
Time (h) Yield
(%)b
1c
2c
1.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
–
CH2Cl2
CH2Cl2
CH2Cl2
DCE
0.5
0.25
0.25
0.25
2
33
75
88
72
82
33
78
59
83
55
70
78
35
39
–
3
–
4
–
5
–
MeCN
THF
6
–
3
7
–
1,4-dioxane
EtOH
2
8
–
3
9d
10d
11d
12d
13d
14d
TFA
AcOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
3
3
TMSOTf
t-BuONa
DBU
3
3
3
K2CO3
3
a Reaction conditions: 1a (1 mmol), PhICl2 (2.2 mmol), 4 Å MS (50 mg),
CH2Cl2 (2 mL), r.t.
b Yield of isolated product.
c The reaction was carried out in the absence of molecular sieves.
d Reaction conditions: 1a (1 mmol), PhICl2 (2.2 mmol), 4 Å MS (50 mg), ad-
ditive (1.0 equiv), CH2Cl2 (2 mL), r.t.
para position of the benzene moiety afforded the corre-
sponding dichlorinated product 2d in 60% yield (Table 2,
entry 4). Replacing the ester group in 1d with a keto car-
bonyl group (substrate 1e) gave the corresponding α,α-di-
chloro dicarbonyl product 2e in 48% yield. The use of 1d
and 1e substrates bearing electron-donating groups at the
para position of the benzene moiety gave reduced yields.
Dicarbonyl compound 1f, without an electron-donating
group at the para position of the benzene ring, gave a high-
er yield (72%) of the corresponding product 2f. Next, vari-
ous β-oxo-N-amides (1g–l) were converted into the corre-
sponding products 2g–l in yields of 70–86% (Table 2, entries
7–12). The reaction conditions appeared to be quite toler-
ant of 3-oxo-N-amides with respect to the electronic nature
of the substituents (electron-withdrawing or electron-
donating groups) and their position on the aryl ring. Next,
several simple substituted ketones were evaluated by ap-
plying the optimized conditions, however, no reactions oc-
curred in these cases (Table 3, entries 1–4).
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Table 2 Investigation of the Scope of the Procedurea
O
O
O
O
PhICl2 (2.2 equiv)
R1
R2
R1
R2
4 Å MS
Cl Cl
CH2Cl2, r.t.
1
2
Entry
1
Substrate
Product
Time (min)
15
Yield (%)b
88
O
O
O
O
1a
2a
Cl Cl
O
O
O
O
2
3
4
1b
1c
1d
2b
2c
2d
20
15
15
77
70
60
OMe
OEt
OMe
OEt
Cl Cl
O
O
O
O
Cl Cl
O
O
O
O
OMe
OMe
Cl Cl
MeO
MeO
MeO
MeO
O
O
O
O
O
5
6
1e
1f
2e
2f
30
30
48
72
Cl Cl
O
O
O
Cl Cl
O
O
O
O
7
8
1g
1h
1i
2g
2h
2i
30
20
30
30
86
70
74
72
N
N
H
H
Cl Cl
OEt
OEt
O
O
O
O
O
O
N
N
H
H
Cl Cl
MeO
O
MeO
O
O
9
N
H
N
H
Cl Cl
OMe
OMe
O
O
O
10
1j
2j
N
N
H
H
Cl Cl
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Synthesis
Table 2 (continued)
Entry
Substrate
Product
Time (min)
25
Yield (%)b
63
O
O
O
O
O
11
1k
1l
2k
N
H
N
H
Cl Cl
Cl
Cl
O
O
O
12
2l
30
83
N
H
N
H
Cl Cl
a Reaction conditions: 1 (1 mmol), PhICl2 (2.2 mmol), 4 Å MS (50 mg), CH2Cl2 (2 mL), r.t.
b Yield of isolated product.
Table 3 Attempted Direct α,α-Dichlorination of Simple Ketones Using
Iodobenzene Dichloride
zene dichloride and elimination of iodobenzene occurs via
the same sequence as described above, to give the dichlori-
nated products 2.
O
In conclusion, we have reported a simple and mild
method for the synthesis of α,α-dichloro-β-dicarbonyl
compounds via the reactions between various β-dicarbonyl
compounds and iodobenzene dichloride in dichlorometh-
ane. The advantages of the described method include the
ready availability of the starting materials, the mild reac-
tion conditions, and economic application to the synthesis
of α,α-dichloro-β-dicarbonyl compounds. Further studies
on the application of this method to other more valuable
compounds, and detailed investigations of the reaction
mechanism are in progress.
PhICl2 (2.2 equiv)
O
Cl
R1
R1
4 Å MS, CH2Cl2
r.t., 30 min
Cl
4
3
Entry Substrate
Product
Yield
(%)
O
O
Cl
1
3a
4a
0
Cl
F
F
O
O
Commercially available, analytical grade reagents and solvents were
used as received. Solvents were purified and dried according to
known procedures. Flash column chromatography was performed
over silica gel (200–300 mesh; Qingdao Haiyang Chemical Co., Ltd)
using EtOAc–PE as the eluent. Petroleum ether (PE) refers to the frac-
tion boiling in the 60–90 °C range. Yields refer to chromatographically
and spectroscopically (1H NMR) homogeneous materials, unless oth-
erwise stated. Melting points were determined with a micromelting
point apparatus and are not corrected. IR spectra were obtained using
a Bio-Rad FTS 6000 Fourier infrared spectrophotometer. 1H and 13C
NMR spectra were recorded on a Bruker AV 400 MHz spectrometer
using CDCl3 as the solvent. The signals were internally referenced to
the residual non-deuterated solvent signal at 7.26 ppm (1H NMR), and
that at 77.16 ppm (13C NMR). Standard abbreviations are used to de-
fine the multiplicities. High-resolution mass spectra (HRMS) were
obtained using an FTICR-MS (Ionspec 7.0T) spectrometer.
Cl
2
3
4
3b
3c
3d
4b
4c
4d
0
0
0
Cl
Br
Br
O
O
Cl
Cl
O
O
Cl
Cl
A possible mechanistic pathway is outlined in Scheme 2.
Dichlorination; General Procedure
Initially, the 1,3-dicarbonyl compound 1 tautomerizes into
its enol isomer B, which reacts with iodobenzene dichloride
to give α-iodo-1,3-dicarbonyl intermediate C. The reductive
removal of iodobenzene from C affords α-chloro-1,3-dicar-
bonyl intermediate D, which tautomerizes into its enol iso-
mer E. Further reaction with a second molecule of iodoben-
To a solution of PhICl2 (2.2 mmol) in anhydrous CH2Cl2 (1 mL) was
added 4 Å MS (50 mg) and the mixture was stirred at r.t. for ca.
15 min. Next, a solution of 1,3-dicarbonyl compound 1 (1 mmol) in
CH2Cl2 (1 mL) was added dropwise and the mixture was stirred at r.t.
until TLC indicated that consumption of the 1,3-dicarbonyl compound
was complete. The reaction mixture was quenched with sat. aq NaH-
CO3 solution and extracted with CH2Cl2 (3 × 10 mL). The combined or-
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O
O
OH
Ph
O
O
O
R1
R2
R1
R2
R1
R2
– PhI
B
I
1
Ph
Cl
Cl
C
I
Cl
OH
O
O
O
O
O
O
O
R1
R2
R1
R2
Cl
R1
R2
R1
R2
– PhI
Cl
I
Cl
Cl Cl
Cl
Ph
E
2
D
Cl
Cl
F
Ph
I
Scheme 2 Proposed mechanistic pathway
ganic phase was dried over anhydrous Na2SO4, filtered, and evaporat-
ed under reduced pressure. The residue was purified by flash column
chromatography on silica gel to give the desired product.
13C NMR (100 MHz, CDCl3): δ = 182.10, 165.03, 164.49, 132.92,
123.23, 114.13, 82.03, 55.77, 55.13.
HRMS (ESI): m/z [M + H]+ calcd for C11H11Cl2O4: 277.0034; found:
277.0030.
2,2-Dichloro-1,3-diphenylpropane-1,3-dione (2a)11
Yield: 257 mg (88%); white solid; mp 59–61 °C (Lit.11 58–59 °C).
1H NMR (400 MHz, CDCl3): δ = 7.98–7.96 (m, 4 H, ArH), 7.55–7.53 (m,
2,2-Dichloro-1-(4-methoxyphenyl)hexane-1,3-dione (2e)
Yield: 138 mg (48%); colorless oil.
2 H, ArH), 7.41–7.37 (m, 4 H, ArH).
13C NMR (100 MHz, CDCl3): δ = 185.46, 134.39, 131.55, 130.59,
IR (neat): 3078, 2968, 2936, 2843, 1746, 1725, 1669, 1599, 1573,
1512, 1259, 1177, 1123, 1028, 854, 609 cm–1
.
128.81, 87.67.
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 9.2 Hz, 2 H, ArH), 6.93 (d, J =
8.8 Hz, 2 H, ArH), 3.87 (s, 3 H), 2.67 (t, J = 7.2 Hz, 2 H), 1.74–1.63 (m, 2
H), 0.90 (t, J = 7.6 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C15H11Cl2O2: 293.0136; found:
293.0132.
13C NMR (100 MHz, CDCl3): δ = 195.09, 184.35, 164.58, 133.26,
123.64, 114.07, 87.30, 55.74, 39.34, 18.11, 13.52.
Methyl 2,2-Dichloro-3-oxo-3-phenylpropanoate (2b)12
HRMS (ESI): m/z [M + H]+ calcd for C13H15Cl2O3: 289.0398; found:
289.0388.
Yield: 257 mg (77%); colorless oil.
1H NMR (400 MHz, CDCl3): δ = 8.04–8.02 (m, 2 H, ArH), 7.63–7.61 (m,
1 H, ArH), 7.49–7.45 (m, 2 H, ArH), 3.85 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 183.36, 164.74, 134.41, 130.75,
130.23, 128.82, 81.78, 55.13.
2,2-Dichloro-1-phenylhexane-1,3-dione (2f)
Yield: 186 mg (72%); colorless oil.
HRMS (ESI): m/z [M + H]+ calcd for C10H9Cl2O3: 246.9929; found:
246.9918.
IR (neat): 3063, 2968, 2935, 2877, 1746, 1708, 1681, 1596, 1580,
1230, 1186, 1126, 689 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 8.0 Hz, 2 H, ArH), 7.62–7.57
(m, 1 H, ArH), 7.49–7.46 (m, 2 H, ArH), 2.71 (t, J = 7.2 Hz, 2 H), 1.70 (m,
2 H), 0.91 (t, J = 7.2 Hz, 3 H).
Ethyl 2,2-Dichloro-3-oxo-3-phenylpropanoate (2c)13
Yield: 182 mg (70%); colorless oil.
13C NMR (100 MHz, CDCl3): δ = 195.08, 185.90, 134.50, 131.17,
130.63, 128.76, 86.91, 39.24, 18.02, 13.49.
HRMS (ESI): m/z [M + NH4]+ calcd for C12H16Cl2O2N: 276.0558; found:
276.0553.
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.0 Hz, 2 H, ArH), 7.61 (t, J =
7.2 Hz, 1 H, ArH), 7.47 (t, J = 8.0 Hz, 2H, ArH), 4.31 (q, J = 7.2 Hz, 2 H),
1.17 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 183.35, 164.18, 134.34, 131.00,
130.21, 128.79, 82.05, 64.81, 13.69.
HRMS (ESI): m/z [M + H]+ calcd for C11H11Cl2O3: 261.0085; found:
261.0080.
2,2-Dichloro-3-oxo-N-phenylbutanamide (2g)5
Yield: 210 mg (86%); white solid; mp 41–42 °C (Lit.5 41–42 °C).
1H NMR (400 MHz, CDCl3): δ = 8.41 (s, 1 H), 7.55 (d, J = 7.6 Hz, 2 H,
ArH), 7.38 (t, J = 7.6 Hz, 2 H, ArH), 7.22 (t, J = 7.2 Hz, 1 H, ArH), 2.54 (s,
3 H).
Methyl 2,2-Dichloro-3-(4-methoxyphenyl)-3-oxopropionate (2d)14
Yield: 156 mg (60%); colorless oil.
13C NMR (100 MHz, CDCl3): δ = 191.82, 160.98, 136.09, 129.38,
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 9.2 Hz, 2 H, ArH), 6.94 (d, J =
126.09, 120.41, 83.29, 24.59.
9.2 Hz, 2 H, ArH), 3.88 (s, 3 H), 3.86 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 777–782

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HRMS (ESI): m/z [M + H]+ calcd for C10H10Cl2NO2: 246.0089; found:
246.0087.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379973.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
2,2-Dichloro-N-(4-ethoxyphenyl)-3-oxobutanamide (2h)4
Yield: 202 mg (70%); white solid; mp 52–55 °C..
1H NMR (400 MHz, CDCl3): δ = 8.34 (s, 1 H), 7.44 (d, J = 8.8 Hz, 2 H,
ArH), 6.88 (t, J = 8.8 Hz, 2 H, ArH), 4.01 (q, J = 7.2, Hz, 2 H), 2.52 (s, 3
H), 1.40 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 191.83, 160.87, 157.03, 128.89,
122.24, 115.01, 83.35, 63.83, 24.55, 14.87.
References
(1) (a) Park, Y.-D.; Kim, J.-J.; Cho, S.-D.; Lee, S.-G.; Falck, J. R.; Yoon,
Y.-J. Synthesis 2005, 1136. (b) Mei, Y.; Bentley, P. A.; Du, J. Tetra-
hedron Lett. 2008, 49, 3802. (c) Fei, N.; Yin, H.; Wang, S.-Z.;
Wang, H.-Q.; Yao, Z.-J. Org. Lett. 2011, 13, 4208. (d) Pitta, B. R.;
Fleming, F. F. Org. Lett. 2010, 12, 2810. (e) Stowers, K. J.; Sanford,
M. S. Org. Lett. 2009, 11, 4584. (f) Yin, Q.; You, S.-L. Org. Lett.
2014, 16, 1810. (g) Bergeron-Brlek, M.; Teoh, T.; Britton, R. Org.
Lett. 2013, 15, 3554. (h) Tunge, J. A.; Mellegaard, S. R. Org. Lett.
2004, 6, 1205. (i) Ayala, C. E.; Villalpando, A.; Nguyen, A. L.;
McCandless, G. T.; Kartika, R. Org. Lett. 2012, 14, 3676.
(2) (a) Voloshchuk, N.; Lee, M. X.; Zhu, W. W.; Tanrikulu, I. C.;
Montclare, J. K. Bioorg. Med. Chem. Lett. 2007, 17, 5907. (b) Park,
J. N.; Ko, S. Y.; Koh, H. Y. Tetrahedron Lett. 2000, 41, 5553.
(c) Loncaric, C.; Wulff, W. D. Org. Lett. 2001, 3, 3675.
(3) (a) Wang, Z.-H.; Zheng, C.; Li, F.; Zhao, L.; Chen, F.-E.; He, Q.-Q.
Synthesis 2012, 44, 699. (b) Wu, G.; Schumacher, D. P.; Tormos,
W.; Clark, J. E.; Murphy, B. L. J. Org. Chem. 1997, 62, 2996.
(c) Wang, Z.; Li, F.; Zhao, L.; He, Q.; Chen, F.; Zheng, C. Tetrahe-
dron 2011, 67, 9199. (d) Lu, W.; Chen, P.; Lin, G. Tetrahedron
2008, 64, 7822.
HRMS (ESI): m/z [M + H]+ calcd for C12H14Cl2NO3: 290.0351; found:
290.0351.
2,2-Dichloro-N-(2-methoxyphenyl)-3-oxobutanamide (2i)4
Yield: 203 mg (74%); white solid; mp 45–46 °C.
1H NMR (400 MHz, CDCl3): δ = 9.17 (s, 1 H), 8.27 (dd, J = 8.0, 1.2 Hz, 1
H, ArH), 7.17–7.13 (m, 1 H, ArH), 7.01–6.97 (m, 1 H, ArH), 6.93 (dd, J =
8.0, 0.8 Hz, 1 H, ArH), 3.94 (s, 3 H), 2.53 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 191.56, 160.58, 148.65, 126.04,
125.67, 121.25, 119.72, 110.35, 83.66, 56.11, 24.45.
HRMS (ESI): m/z [M + H]+ calcd for C11H12Cl2NO3: 276.0194; found:
276.0192.
2,2-Dichloro-N-(4-methoxyphenyl)-3-oxobutanamide (2j)5
Yield: 198 mg (72%); white solid; mp 43–45 °C (Lit.5 42–44 °C).
1H NMR (400 MHz, CDCl3): δ = 8.41 (s, 1 H), 7.44 (d, J = 9.2 Hz, 2 H,
ArH), 6.88 (d, J = 8.8 Hz, 2 H, ArH), 3.79 (s, 3 H), 2.51 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 191.81, 160.94, 157.65, 129.06,
(4) Liu, W.; Tan, L.; Zhou, P.; Chen, C.; Zhang, Q. Synthesis 2013, 45,
2600.
(5) Wang, J.; Li, H.; Zhang, D.; Huang, P.; Wang, Z.; Zhang, R.; Liang,
Y.; Dong, D. Eur. J. Org. Chem. 2013, 5376.
(6) Kim, J.-J.; Kweon, D.-K.; Cho, S.-D.; Kim, H.-K.; Lee, S.-G.; Yoo, Y.-
J. Synlett 2006, 194.
122.33, 114.42, 83.33, 55.58, 24.48.
HRMS (ESI): m/z [M + H]+ calcd for C11H12Cl2NO3: 276.0194; found:
(7) For selected reviews on hypervalent iodine chemistry and
organic polyvalent iodine compounds, see: (a) Samanta, R.;
Matcha, K.; Antonchick, A. P. Eur. J. Org. Chem. 2013, 5769.
(b) Stang, P. J.; Zhdankin, V. V. Chem. Rev. 1966, 66, 243.
(c) Stang, P. J. Chem. Rev. 1996, 96, 1123. (d) Wirth, T.; Hirt, U. H.
Synthesis 1999, 1271. (e) Zhdankin, V. V.; Stang, P. J. Chem. Rev.
2002, 102, 2523. (f) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008,
108, 5299.
276.0192.
2,2-Dichloro-3-oxo-N-(o-tolyl)butanamide (2k)5
Yield: 163 mg (63%); white solid; mp 61–63 °C (Lit.5 62–65 °C).
1H NMR (400 MHz, CDCl3): δ = 8.29 (s, 1 H), 7.71 (d, J =8.4 Hz, 1 H,
ArH), 7.23–7.19 (m, 3 H, ArH), 2.56 (s, 3 H), 2.29 (s, 3 H).
2,2-Dichloro-N-(4-chlorophenyl)-3-oxobutanamide (2l)4
Yield: 231 mg (83%); white solid; mp 62–64 °C (Lit.15 62–63 °C).
(8) Liu, L.; Zhang-Negrerie, D.; Du, Y.; Zhao, K. Org. Lett. 2014, 16,
436.
(9) (a) Yu, J.; Zhang, C. Synthesis 2009, 2324. (b) Heasley, V. L.; Rold,
K. D.; McKee, D. B.; Heasley, G. E. J. Org. Chem. 1976, 41, 1287.
(c) Zanka, A.; Takeuchi, H.; Kubota, A. Org. Process Res. Dev.
1998, 2, 270. (d) Kalyani, D.; Sanford, M. S. J. Am. Chem. Soc.
2008, 130, 2150. (e) Kalyani, D.; Satterfield, A. D.; Sanford, M. S.
J. Am. Chem. Soc. 2010, 132, 8419. (f) Nicolaou, K. C.; Simmons,
N. L.; Ying, Y. C.; Heretsch, P. M.; Chen, J. S. J. Am. Chem. Soc.
2011, 133, 8134. (g) Tao, J.; Tran, R.; Murphy, G. K. J. Am. Chem.
Soc. 2013, 135, 16312.
1H NMR (400 MHz, CDCl3): δ = 8.43 (s, 1 H), 7.50 (d, J = 8.8 Hz, 2 H,
ArH), 7.33 (d, J = 8.8 Hz, 2 H, ArH), 2.54 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 191.98, 161.05, 134.71, 131.30,
129.43, 121.79, 83.10, 24.55.
HRMS (ESI): m/z [M + H]+ calcd for C10H9Cl3NO2: 279.9699; found:
279.9698.
(10) Stuurman, N. F.; Conradie, J. J. Organomet. Chem. 2009, 694, 259.
(11) Sokolov, S. D.; Rudchenko, V. F.; Turchin, K. F.; Pleshkova, A. P.;
Zolotoi, A. B. Dokl. Chem. 1981, 258, 249.
(12) Mei, Z.-W.; Omote, T.; Mansour, M.; Kawafuchi, H.; Takaguchi,
Y.; Jutand, A.; Tsuboi, S.; Inokuchi, T. Tetrahedron 2008, 64,
10761.
Acknowledgment
We acknowledge the Scientific Research Foundation of Henan Univer-
sity of Science and Technology (2014QN022, 09001680) and the
Foundation of Scientific and Technological Project of Henan Province
(082102330019).
(13) Kitamura, T.; Tazawa, Y.; Morshed, M. H.; Kobayashi, S. Synthesis
2012, 44, 1159.
(14) Matsuki, M.; Sobukawa, M.; Kawai, A.; Inoue, H.; Takeda, M.
Chem. Pharm. Bull. 1993, 41, 643.
(15) Hodgkinson, A. J.; Staskun, B. J. Org. Chem. 1969, 34, 1709.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 777–782