Potassium carbonate catalyzed regioselective aminohalogenation of β-nitrostyrenes by using benzyl carbamate/N-chlorosuccinimide as a new nitrogen/chlorine source

Article abstract of DOI:10.1055/s-0030-1260245

A combination of benzyl carbamate and N-chlorosuccinimide was developed as a new system for aminohalogenation of β-nitrostyrenes catalyzed by potassium carbonate in dichloromethane at room temperature. The reaction tolerates a wide range of substituents o

Full text of DOI:10.1055/s-0030-1260245

3680
PAPER
Potassium Carbonate Catalyzed Regioselective Aminohalogenation of
b-Nitrostyrenes by Using Benzyl Carbamate/N-Chlorosuccinimide as a
New Nitrogen/Chlorine Source
Xiaoyun Ji,a Haibo Mei,a Yu Qian,a Jianlin Han,*a Guigen Li,a,c Yi Pan*a,b
a
School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. of China
Fax +86(25)83593153 ; E-mail: hanjl@nju.edu.cn; fax +86(25)83592846; E-mail: yipan@nju.edu.cn
State Key Lab of Coordination Chemistry, Nanjing University, Nanjing 210093, P. R. of China
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
b
c
Received 29 July 2011; revised 18 August 2011
In subsequent decades, very few reports on these types of
reaction appeared,3f mainly because of their moderate
chemical yields and low regioselectivities. Although, re-
cent studies on aminohalogenation of b-nitrostyrenes with
Abstract: A combination of benzyl carbamate and N-chlorosuccin-
imide was developed as a new system for aminohalogenation of b-
nitrostyrenes catalyzed by potassium carbonate in dichloromethane
at room temperature. The reaction tolerates a wide range of substit-
uents on the b-nitrostyrene, and proceeds smoothly in good-to- similar nitrogen sources have reported marked improve-
excellent chemical yields (77–99%). The new system shows a high
ments in regio- and stereoselectivities, the transforma-
efficiency and it markedly shortens the reaction time for aminochlo-
tions usually suffer from long reaction times of more than
rination. N,N-Dichlorobenzyl carbamate was also found to be a
24 hours.10a–d,11 The efficient and selective aminohaloge-
highly efficient source of both nitrogen and chlorine for the amino-
nation of b-nitrostyrenes, therefore, still remains an im-
halogenation reaction.
portant and challenging problem. In our work on the
Key words: aminations, chlorinations, alkenes, carbamates,
aminohalogenation reaction, we found that benzyl car-
amides
bamate can be used as an efficient source of nitrogen for
the aminohalogenation of b-nitrostyrenes. Here, we
would like to report a simple and highly efficient ami-
Aminohalogenations and related reactions of functional-
ized olefins are becoming increasingly useful as tools for
nochlorination of b-nitrostyrenes with benzyl carbamate
(CbzNH2, 1) as a new source of nitrogen in the presence
of potassium carbonate as a catalyst (Scheme 1). This new
the simultaneous construction of C–N and C–halogen
bonds in a tandem fashion.1–4 The resulting vicinal ha-
reaction can be complete within eight hours, which great-
loamines belong to an important class of building blocks
ly shortens the reaction time. It also gives higher yields
in both organic synthesis and medicinal chemistry.5 The
than the previous methods.7–11
products can also be readily converted into numerous oth-
er valuable derivatives by replacing the halogen atoms
through either intramolecular or intermolecular substitu-
O
O
O
NH2
tion reactions.6 In the past decade, many new catalytic
systems have been developed for the aminohalogenation
of a range of functionalized alkenes, such as a,b-unsatur-
ated carboxylic esters,7 a,b-unsaturated nitriles,8 or a,b-
unsaturated ketones.9 However, the sources of nitrogen
for these aminohalogenation reactions lack diversity, as
sulfonamides are used in most cases.7–9 Recently, b-ni-
trostyrenes, which are a particularly important class of
substrates, were reported to undergo aminohalogenation
and, as a result, they have attracted a great deal of research
interest.10,11 Furthermore, the resulting haloamine prod-
ucts can be easily converted into the corresponding vicinal
diamines.12
HN
O
Ph
K2CO3, CH2Cl2, r.t.
within 8 h
1
NO2
Cl
+
Ar
Cl
NO2
NCS
3
+
Ar
up to 99% chemical yields
2
Scheme 1 Aminohalogenation with benzyl carbamate as a nitrogen
source
In the initial study, we used b-nitrostyrene (2a) as the
starting material under the previous aminochlorination
conditions.10 The reaction was carried out at room temper-
ature with benzyl carbamate as a nitrogen source and N-
chlorosuccinimide (NCS) as a source of chlorine with 4-
(N,N-dimethylamino)pyridine as the catalyst in dichlo-
romethane without protection by an inert atmosphere. No
reaction was detected and most of the starting materials
remained even with a prolonged reaction time (Table 1,
entry 1). We then examined triphenylphosphine as an al-
ternative organocatalyst (entry 2) and several metal cata-
lysts (entries 3–5), but almost none of the desired
haloamine products were obtained. Further optimization
of the catalyst showed that the transformation proceeds
In the 1960s, N,N-dichlorocarbamates were used for ami-
nohalogenation of simple or electron-deficient olefins.13
This pioneering work showed that the reaction has many
of the characteristics of a free-radical addition reaction.13a
SYNTHESIS 2011, No. 22, pp 3680–3686
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x.
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Advanced online publication: 29.09.2011
DOI: 10.1055/s-0030-1260245; Art ID: H74711SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Aminohalogenation of b-Nitrostyrenes
3681
Table 1 Aminohalogenation of 2a with Various Catalysts
Table 2 Optimization of Conditions for Aminohalogenation of 2a
O
O
O
O
HN
O
Ph
HN
O
Ph
NO2
+
cat.
O
NH2
NO2
+
NO2
Cl
NO2
Cl
K2CO3
NCS
+
O
NH2
CH2Cl2
r.t.
NCS
+
Cl
Cl
2a
1
3a
2a
1
3a
Entrya
Catalyst (mol%)
DMAP (20%)
Ph3P (20%)
Time (h)
24
Yield (%)b
NRc
NR
NR
NR
NR
94
Entrya 2a/CbzNH2/NCS Temp
Solvent
Time Yield
(equiv)
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:1:2
1:2:2
1:1:3
1:2:3
(°C)
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
45
(h)
10
10
10
10
10
10
10
7
(%)b
1
2
1
2
CH2Cl2
toluene
THF
94
24
61
3
CuCl (20%)
24
3
89
4
Ni(OAc)2 (20%)
24
4
DMSO
MeOH
MeCN
DMF
NRc
29
5
Mn(OAc)2 (20%)
K2CO3 (20%)
K2CO3 (10%)
K2CO3 (15%)
K2CO3 (30%)
KOH (20%)
24
5
6
10
6
88
7
10
63
7
NR
65
8
10
85
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
9
10
94
9
8
93
10
24
88
10
11
12
13
14
15
16
17
9
94
a Conditions: 2a (0.5 mmol), NCS (1.5 mmol), CbzNH2 (1.5 mmol),
CH2Cl2 (3 mL), r.t.
3
35
b Isolated yield.
c NR = no reaction was observed.
45
5
88
45
7
95
smoothly in the presence of 20 mol% of potassium car-
bonate, giving the desired product 3a in 94% yield, with
the reaction going to completion within ten hours (entry
6). The amount of catalyst was found to be critical for the
reaction, and lower chemical yields were obtained when
10 or 15 mol% of potassium carbonate was used (entries
7 and 8). Although potassium hydroxide was also found to
work well as a catalyst in the reaction, giving a good
chemical yield (88%), 24 hours were needed before the
starting material was completely consumed (entry 10).
r.t.
r.t.
r.t.
r.t.
8
46
8
70
8
31
8
79
a Conditions: 2a (0.5 mmol), K2CO3 (20 mol%), solvent (3 mL).
b Isolated yield.
c NR = no reaction was observed.
decreasing the amount of any one of them resulted in a
lower yield (entries 14–17).
We then examined various solvents with potassium car-
bonate as catalyst to improve the efficiency of the reaction
(Table 2). The solvent was found to play an important role
in the system and the choice of solvent had a marked ef-
fect on the yield. No aminohalogenation product was ob-
tained when N,N-dimethylformamide or dimethyl
sulfoxide was used (entries 4 and 7). The reaction in tet-
rahydrofuran or acetonitrile as solvent was also complete
within ten hours, but the yields were slightly lower (en-
tries 3 and 6). Dichloromethane was the best choice of sol-
vent, giving the highest yield (94%; entry 1). After careful
studies, we found that the reaction time could even be re-
duced to eight hours with an excellent yield (93%; entry
9), whereas a shorter reaction time resulted in a lower
yield (65%; entry 8). Increasing the temperature did not
have much effect on the efficiency of the reaction, al-
though it was complete within a slightly shorter time (en-
tries 11–13). The use of three equivalents each of benzyl
carbamate and NCS was necessary for the reaction, and
Having optimized the conditions for the aminohalogena-
tion reaction, we examined its scope by using a variety of
b-nitrostyrenes (Table 3). The reaction proceeded
smoothly with a wide range of substrates, resulting in
good-to-excellent chemical yields (77–99%). The substit-
uent groups on the aromatic rings did not have much ef-
fect on the reaction. Both electron-rich and electron-
deficient substrates were suitable for the reaction, and ex-
cellent yields were obtained with fluoro (entries 7 and 10),
trifluoromethyl (entry 11), or methoxy (entries 17 and 18)
substituents. Surprisingly, in the case of the 4-chloro de-
rivative 2d and the 3-bromo derivative 2e, the reaction
needed a longer time before all the starting materials were
consumed (entries 4 and 5). We then examined a substrate
with a disubstituted aromatic ring 2h, and we found it also
worked well, giving an excellent yield of the correspond-
ing product (99%; entry 8). Note also that the 1-naphthyl
Synthesis 2011, No. 22, 3680–3686 © Thieme Stuttgart · New York

3682
X. Ji et al.
PAPER
analogue 2l also gave a high chemical yield (99%; entry
12). Furthermore, excellent regioselectivities were detect-
ed in all the cases, and a single regioisomer was obtained
from each reaction.
Table 3 Scope of the Aminohalogenation Reaction
O
O
K2CO3
HN
O
Ph
NO2
(20 mol%)
Ar
O
NH2
NO2
Cl
+
NCS
+
Ar
CH2Cl2, r.t.
2
1
3
Cl
Entrya Substrate Ar
Time (h) Product Yield (%)b
1
2
2a
2b
2c
2d
2e
2f
Ph
8
8
3a
3b
3c
3d
3e
3f
94
99
99
87
90
99
99
99
87
93
89
99
91
79
77
93
97
97
91
2-ClC6H4
3-ClC6H4
4-ClC6H4
3-BrC6H4
2-BrC6H4
4-FC6H4
Figure 1 ORTEP diagram for compound 3a
3
8
bamate/NCS system. Furthermore, this system also gave
excellent regioselectivities, and only one regioisomer was
obtained from each of the b-nitrostyrenes that we exam-
ined.
4
20
32
8
5
6
On the basis of a previous report on the aminohalogena-
tion of b-nitrostyrene,10 and the regioselectivity that we
obtained with the current aminohalogenation system, we
propose that the reaction proceeds by a pathway involving
a Michael addition (Scheme 2).
7
2g
2h
2i
8
3g
3h
3i
8
3-Br-4-MeOC6H3
4-BrC6H4
8
9
8
In the initial step, potassium carbonate reacts with benzyl
carbamate to give the intermediate A, which adds to the a-
position of b-nitrostyrene (2a), giving the Michael inter-
mediate B. The Cl+ cation derived from NCS adds to the
negatively charged intermediate B, giving the monohalo
amine intermediate C. The final step is the formation of
the dichlorinated compound 3a by deprotonation/electro-
philic chlorination of precursor D.14 The reaction with the
N,N-dichlorobenzyl carbamate as the nitrogen/chlorine
10
11
12
13
14
15
16
17
18
19
2j
3-FC6H4
8
3j
2k
2l
4-F3CC6H4
1-naphthyl
4-NCC6H4
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-MeOC6H4
4-MeOC6H4
2-BnOC6H4
8
3k
3l
8
2m
2n
2o
2p
2q
2r
2s
8
3m
3n
3o
3p
3q
3r
3s
8
8
8
Table 4 Aminochlorination of b-Nitrostyrene Derivatives with
N,N-Dichlorobenzyl Carbamate
8
O
O
8
K2CO3
(20 mol%)
HN
O
Ph
O
NCl2
NO2
+
Ar
8
NO2
Cl
CH2Cl2, r.t.
Ar
a Conditions: substrate (0.5 mmol), NCS (1.5 mmol), CbzNH2 (1.5
mmol), K2CO3 (20 mol%), CH2Cl2 (3 mL), r.t.
b Isolated yield.
2
1
3
Cl
Entrya
Substrate Ar
Time
(h)
Product Yield
(%)b
1
2
3
4
5
6
7
2a
2c
2f
Ph
8
8
8
8
8
8
8
3a
3c
3f
99
99
99
89
95
99
91
The structure of the resulting dichlorinated halo amides
was unambiguously confirmed by X-ray diffraction anal-
ysis of the phenyl derivative 3a (Figure 1).
3-ClC6H4
2-BrC6H4
4-FC6H4
Next we tried to develop a better system for the aminoha-
logenation of b-nitrostyrenes (Table 4) by using N,N-
dichlorobenzyl carbamate (CbzNCl2) as the source of ni-
trogen and chlorine instead of a combination of benzyl
carbamate and NCS. As shown in Table 4, the reaction
was complete within eight hours for all the substrates ex-
amined, and the desired halo amide products were ob-
tained in high chemical yields. In the cases of 2a, 2k, and
2n, the yields were higher than those from the benzyl car-
2g
2k
2l
3g
3k
3l
4-F3CC6H4
1-naphthyl
2-MeC6H4
2n
3n
a Conditions: substrate (0.5 mmol), CbzNCl2 (1 mmol), K2CO3 (20
mol%), CH2Cl2 (3 mL), at r.t.
b Isolated yield.
Synthesis 2011, No. 22, 3680–3686 © Thieme Stuttgart · New York

PAPER
Aminohalogenation of b-Nitrostyrenes
3683
O
ous phase was extracted with EtOAc (3 × 25 mL) and the combined
organic phase was dried (Na2SO4). The solvent was removed to give
a crude product that was purified by TLC (PE–EtOAc, 4:1).
O
K2CO3
O
NH
O
NH2
A
Benzyl (2,2-Dichloro-2-nitro-1-phenylethyl)carbamate (3a)
White solid; yield: 98%; mp 85–87 °C.
NHCbz
NO2
NO2
NHCbz
NO2
NCS
Ph
Ph
2a
IR (KBr): 3418, 3290, 3034, 2927, 1603, 1694, 1583, 1249, 1050
cm–1.
Ph
C
Cl
B
1H NMR (300 MHz, CDCl3): d = 7.27–7.50 (m, 10 H), 6.02 (d,
J = 10.2 Hz, 1 H), 5.76 (d, J = 9.7 Hz, 1 H), 5.01–5.19 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 155.26, 135.59, 132.88, 129.93,
128.99, 128.83, 128.69, 128.54, 128.36, 115.81, 68.01, 64.46.
NHCbz
NCS
NO2
Cl
Ph
Cl
3a
HRMS (ESI): m/z [M + Na]+ calcd for C16H14Cl2N2NaO4: 391.0223;
Scheme 2 Proposed mechanism for the reaction
found: 360.0225.
Crystallographic data for compound 3a have been deposited with
the Cambridge Crystallographic Data Centre as supplementary pub-
lication CCDC 825669; copies can be obtained free of charge on ap-
plication to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:
+44(1223)336033 or email: deposit@ccdc.cam.ac.uk].
source is presumably to proceed through a previously re-
ported chloronium process.10a
In summary, the regioselective aminochlorination of b-ni-
trostyrenes with a combination of benzyl carbamate as a
nitrogen source and NCS as a source of chlorine under
mild catalytic conditions has been developed. The synthe-
sis is convenient to perform because it is catalyzed by po-
tassium carbonate at room temperature and does not
require protection by an inert gas. The new process is
highly efficient, and only eight hours is needed to com-
plete the reaction. Good chemical yields and excellent re-
gioselectivities can be achieved with a wide range of b-
nitrostyrenes. Further studies on this new system will fo-
cus on the aminohalogenation of a,b-unsaturated carbox-
ylic ester and ketones.
Benzyl [2,2-Dichloro-1-(2-chlorophenyl)-2-nitroethyl]carbam-
ate (3b)
White solid; yield: 99%; mp 83–85 °C.
IR (KBr): 3413, 3304, 3035, 2973, 1710, 1587, 1526, 1235, 1060
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.66–7.13 (m, 9 H), 6.81 (d,
J = 10.2 Hz, 1 H), 5.83 (d, J = 10.1 Hz, 1 H), 5.17–4.92 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 154.63, 135.60, 135.32, 131.88,
130.93, 130.36, 129.71, 128.63, 128.53, 128.43, 127.35, 115.19,
68.09, 59.54.
HRMS (ESI): m/z [M + Na]+ calcd for C16H13Cl3N2NaO4: 424.9833;
found: 424.9836.
Unless otherwise stated, all reagents were purchased from commer-
cial sources and used without further purification. CbzNCl2 was
prepared according to the literature.15 The progress of the reactions
was monitored by TLC on silica gel 60F-254 with detection by UV.
Flash chromatography was performed using silica gel 60 (200–300
mesh) with freshly distilled solvents. Melting points are uncorrect-
ed. IR spectra were recorded on a Bruker Vector 22 spectrometer in
Benzyl [2,2-Dichloro-1-(3-chlorophenyl)-2-nitroethyl]carbam-
ate (3c)
White solid; yield: 99%; mp 104–105 °C.
IR (KBr): 3415, 3314, 3066, 2961, 1716, 1587, 1506, 1330, 1229,
1050 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.57–7.15 (m, 9 H), 6.04 (d,
J = 10.4 Hz, 1 H), 5.80 (d, J = 9.9 Hz, 1 H), 5.06–5.13 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 154.74, 135.26, 134.76, 130.12,
130.00 (2 C), 128.94, 128.68, 128.62, 128.41, 127.16, 114.94,
68.17, 63.68.
1
KBr pellets. H and 13C NMR spectra were recorded on a Bruker
ARX300 spectrometer with TMS as the internal standard. High-
resolution mass spectra for all the new compounds were obtained by
using a MicroMass Q-Tof instrument in the ESI mode. The crystal
structure was recorded on an X-ray diffraction spectrometer.
HRMS (ESI): m/z [M + Na]+ calcd for C16H13Cl3N2NaO4: 424.9833;
found: 424.9835.
Aminohalogenation of b-Nitrostyrenes with CbzNH2/NCS;
Typical Procedure
A dry round-bottomed flask was charged with the b-nitrostyrene
(0.5 mmol), NCS (1.5 mmol), CbzNH2 (1.5 mmol), and anhyd
K2CO3 (0.1 mmol). CH2Cl2 (3 mL) was then added and the soln was
stirred at r.t., with no protection by inert gas, until the reaction was
complete (TLC). Sat. aq Na2SO3 (3 mL) was added to quench the
reaction. The aqueous phase was extracted with EtOAc (3 × 25 mL)
and the combined organic phase was dried (Na2SO4). The solvent
was removed to give a crude product that was purified by TLC (PE–
EtOAc, 4:1).
Benzyl [2,2-Dichloro-1-(4-chlorophenyl)-2-nitro]ethylcarbam-
ate (3d)
White solid; yield: 87%; mp 70–71 °C.
IR (KBr): 3420, 3319, 3065, 2961, 1717, 1587, 1493, 1332, 1228,
1094, 1050 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.33–7.38 (m, 9 H), 6.03 (d,
J = 9.8 Hz, 1 H), 5.80 (d, J = 9.2 Hz, 1 H), 5.05–5.13 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 154.75, 136.13, 135.30, 131.30,
130.15, 129.04, 128.68, 128.62, 128.39, 115.10, 68.13, 63.66.
Aminohalogenation of b-Nitrostyrenes with N,N-Dichloroben-
zyl Carbamate; Typical Procedure
HRMS (ESI): m/z [M + Na]+ calcd for C16H13Cl3N2NaO4: 424.9833;
A dry round-bottomed flask was charged with the b-nitrostyrene
(0.5 mmol), CbzNCl2 (1 mmol), and anhyd K2CO3 (0.1 mmol).
CH2Cl2 (3 mL) was then added and the soln was stirred at r.t. with
no protection by inert gas until the reaction was complete (TLC).
Sat. aq Na2SO3 (3 mL) was added to quench the reaction. The aque-
found: 424.9836.
Benzyl [1-(3-Bromophenyl)-2,2-dichloro-2-nitroethyl]carbam-
ate (3e)
White solid; yield: 90%; mp 87–89 °C.
Synthesis 2011, No. 22, 3680–3686 © Thieme Stuttgart · New York

3684
X. Ji et al.
PAPER
IR (KBr): 3408, 3305, 3034, 2961, 1706, 1586, 1331, 1233, 1050
cm–1.
13C NMR (75 MHz, CDCl3): d = 154.80, 135.31, 132.00, 131.85,
130.44, 128.68, 128.61, 128.37, 124.36, 115.03, 68.13, 63.76.
1H NMR (300 MHz, CDCl3): d = 7.78–7.17 (m, 9 H), 5.93–6.03 (m,
2 H), 5.03–5.11 (m, 2 H).
HRMS (ESI): m/z [M + Na]+ calcd for C16H13BrCl2N2NaO4:
468.9328; found: 468.9324.
13C NMR (75 MHz, CDCl3): d = 154.89, 135.31, 135.06, 133.04,
131.88, 130.27, 128.69, 128.61, 128.38, 127.71, 122.77, 115.05,
68.19, 63.70.
HRMS (ESI): m/z [M + Na]+ calcd for C16H13BrCl2N2NaO4:
468.9328; found: 468.9343.
Benzyl [2,2-Dichloro-1-(3-fluorophenyl)-2-nitroethyl]carbam-
ate (3j)
White solid; yield: 93%; mp 96–98 °C.
IR (KBr): 3419, 3317, 3035, 2962, 1716, 1587, 1506, 1336, 1233,
1049 cm–1.
Benzyl [1-(2-Bromophenyl)-2,2-dichloro-2-nitroethyl]carbam-
ate (3f)
1H NMR (300 MHz, CDCl3): d = 7.54–7.01 (m, 9 H), 6.09 (d,
J = 9.3 Hz, 1 H), 5.89 (d, J = 9.3 Hz, 1 H), 5.14 (m, 2 H).
White solid; yield: 99%; mp 62–63 °C.
1
13C NMR (75 MHz, CDCl3): d = 162.54 (d, JCF = 248.1 Hz),
IR (KBr): 3413, 3308, 3065, 2966, 1714, 1587, 1507, 1335, 1231,
1054 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.69 (d, J = 7.6 Hz, 1 H), 7.51 (d,
J = 7.1 Hz, 1 H), 7.45–7.20 (m, 7 H), 6.86 (d, J = 10.0 Hz, 1 H),
5.77 (d, J = 10.0 Hz, 1 H), 5.28–4.93 (m, 2 H).
154.91, 135.34, 135.13 (d, 3JCF = 6.6 Hz), 130.38 (d, 3JCF = 7.9 Hz),
128.67, 128.60, 128.37, 124.84, 116.98 (d, 2JCF = 21.2 Hz), 116.04
(d, 2JCF = 22.8 Hz), 115.9, 68.09, 63.66.
HRMS (ESI): m/z [M + Na]+ calcd for C16H13Cl2FN2NaO4:
409.0129; found: 409.0123.
13C NMR (75 MHz, CDCl3): d = 154.61, 135.31, 133.75 (2 C),
131.15, 128.62, 128.55, 128.47, 127.97, 126.47, 115.23, 68.11,
61.86.
HRMS (ESI): m/z [M + Na]+ calcd for C16H13BrCl2N2NaO4:
468.9328; found: 468.9326.
Benzyl {2,2-Dichloro-2-nitro-1-[4-(trifluoromethyl)phenyl]eth-
yl}carbamate (3k)
Colorless oil; yield: 89%.
IR (KBr): 3408, 3308, 3036, 2964, 1711, 1587, 1533, 1327, 1237,
1130, 1070 cm–1.
Benzyl [2,2-Dichloro-1-(4-fluorophenyl)-2-nitroethyl]carbam-
ate (3g)
White solid; yield: 99%; mp 73–75 °C.
1H NMR (300 MHz, CDCl3): d = 7.69 (d, J = 8.2 Hz, 2 H), 7.58 (d,
J = 8.1 Hz, 2 H), 7.32–7.35 (m, 5 H), 6.12 (d, J = 10.1 Hz, 1 H),
5.95 (d, J = 10.0 Hz, 1 H), 5.22–5.04 (m, 2 H).
IR (KBr): 3420, 3314, 3035, 2963, 1713, 1585, 1511, 1329, 1228,
1166, 1051 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.52–7.29 (m, 7 H), 7.21–6.96 (m,
2 H), 6.04 (d, J = 10.1 Hz, 1 H), 5.80 (d, J = 10.1 Hz, 1 H), 5.23–
5.03 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 154.85, 136.77, 135.27, 131.99 (q,
2JCF = 32.8 Hz), 129.45, 128.68, 128.64, 128.35, 125.72 (q,
3JCF = 3.0 Hz), 123.64 (q, 1JCF = 272.3 Hz), 114.84, 68.20, 63.83.
HRMS (ESI): m/z [M + Na]+ calcd for C17H13Cl2F3N2NaO4:
459.0097; found: 459.0094.
13C NMR (75 MHz, CDCl3): d = 163.44 (d, JCF = 250.3 Hz),
1
Benzyl [2,2-Dichloro-1-(naphth-1-yl)-2-nitroethyl]carbamate
(3l)
White solid; yield: 99%; mp 96–98 °C.
154.89, 135.38, 130.77 (d, 3JCF = 8.6 Hz), 128.75, 128.67, 128.59,
128.36, 115.89 (d, 2JCF = 21.8 Hz), 115.38, 68.09, 63.66.
HRMS (ESI): m/z [M + Na]+ calcd for C16H13Cl2FN2NaO4:
409.0129; found: 409.0123.
IR (KBr): 3413, 3315, 3035, 2958, 1713, 1503, 1326, 1232, 1057
cm–1.
Benzyl [1-(3-Bromo-4-methoxyphenyl)-2,2-dichloro-2-nitro-
ethyl]carbamate (3h)
Colorless oil; yield: 99%.
1H NMR (300 MHz, CDCl3): d = 8.36 (d, J = 8.1 Hz, 1 H), 7.87–
7.93 (m, 2 H), 7.47–7.67 (m, 4 H), 7.24–7.30 (m, 5 H), 7.08–7.11
(m, 1 H), 5.85 (d, J = 9.6 Hz, 1 H), 5.07–5.10 (m, 2 H).
IR (KBr): 3405, 3314, 3033, 2961, 1713, 1585, 1498, 1293, 1259,
1230, 1056 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.65 (d, J = 2.2 Hz, 1 H), 7.45–
7.28 (m, 6 H), 6.90 (t, J = 7.5 Hz, 1 H), 6.00 (d, J = 10.1 Hz, 1 H),
5.88 (d, J = 9.5 Hz, 1 H), 5.24–5.01 (m, 2 H), 3.92 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 155.09, 135.39, 133.75, 131.96,
130.63, 130.33, 129.05, 128.63, 128.52, 128.38, 127.48, 126.42,
125.40, 124.95, 123.17, 116.14, 68.05, 57.98.
HRMS (ESI): m/z [M + Na]+ calcd for C20H16Cl2N2NaO4: 441.0379;
found: 441.0382.
13C NMR (75 MHz, CDCl3): d = 157.01, 154.86, 135.36, 133.42,
129.45, 128.67, 128.57, 128.36, 126.15, 115.37, 111.96, 111.63,
68.09, 63.32, 56.35.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15BrCl2N2O5Na:
498.9434; found: 498.9438.
Benzyl [2,2-Dichloro-1-(4-cyanophenyl)-2-nitroethyl]carbam-
ate (3m)
Colorless oil; yield: 91%.
IR (KBr): 3320, 3065, 2961, 2232, 1732, 1586, 1509, 1231, 1051
cm–1.
Benzyl [1-(4-Bromophenyl)-2,2-dichloro-2-nitroethyl]carbam-
ate (3i)
White solid; yield: 87%; mp 70–72 °C.
1H NMR (300 MHz, CDCl3): d = 7.65 (d, J = 8.1 Hz, 2 H), 7.54 (d,
J = 8.2 Hz, 2 H), 7.24–7.32 (m, 5 H), 6.11 (d, J = 9.4 Hz, 1 H), 5.97
(d, J = 9.2 Hz, 1 H), 5.05–5.09 (m, 2 H).
IR (KBr): 3405, 3311, 3065, 2962, 1713, 1585, 1515, 1491, 1330,
1233, 1076 cm–1.
13C NMR (75 MHz, CDCl3): d = 154.77, 137.87, 135.19, 132.44,
129.79, 128.69, 128.33, 117.90, 114.51, 113.91, 68.26, 63.83.
1H NMR (300 MHz, CDCl3): d = 7.55 (d, J = 8.4 Hz, 2 H), 7.32 (m,
7 H), 6.04 (d, J = 10.1 Hz, 1 H), 5.84–5.88 (b, 1 H), 5.04–5.12 (m,
2 H).
HRMS (ESI): m/z [M + Na]+ calcd for C17H13Cl2N3NaO4: 416.0175;
found: 416.0213.
Synthesis 2011, No. 22, 3680–3686 © Thieme Stuttgart · New York

PAPER
Aminohalogenation of b-Nitrostyrenes
3685
Benzyl [2,2-Dichloro-2-nitro-1-(2-tolyl)ethyl]carbamate (3n)
Colorless oil; yield: 79%.
1H NMR (300 MHz, CDCl3): d = 7.29–7.33 (m, 7 H), 6.87 (d,
J = 8.6 Hz, 2 H), 5.95 (d, J = 10.0 Hz, 1 H), 5.77 (d, J = 10.3 Hz, 1
H), 5.24–5.02 (m, 2 H), 3.79 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 160.63, 154.95, 135.50, 130.05,
128.64, 128.52, 128.37, 124.63, 115.82, 114.14, 67.95, 63.87,
55.34.
IR (KBr): 3406, 3304, 3032, 2964, 1768, 1704, 1584, 1507, 1230,
1044 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.45 (d, J = 7.4 Hz, 1 H), 7.21–
7.29 (m, 8 H), 6.43 (d, J = 10.0 Hz, 1 H), 5.78 (d, J = 9.7 Hz, 1 H),
4.97–5.08 (m, 2 H), 2.58 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C17H16Cl2N2NaO5: 421.0328;
found: 421.0325.
13C NMR (75 MHz, CDCl3): d = 155.01, 138.17, 135.43, 132.63,
131.20, 129.64, 128.65, 128.53, 128.36, 126.62, 126.46, 115.97,
67.98, 59.14, 20.29.
HRMS (ESI): m/z [M + Na]+ calcd for C17H16Cl2N2NaO4: 405.0379;
found: 405.0377.
Benzyl {1-[2-(Benzyloxy)phenyl]-2,2-dichloro-2-nitroethyl}car-
bamate (3s)
Colorless oil; yield: 91%.
IR (KBr): 3416, 3319, 3065, 3034, 2953, 2888, 1732, 1585, 1498,
1228, 1045 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.42–7.29 (m, 12 H), 6.95–7.00
(m, 2 H), 6.38–6.46 (m, 2 H), 5.07–5.09 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 156.95, 155.23, 136.06, 135.78,
131.11, 130.89, 128.85, 128.60, 128.36, 128.32, 128.23, 127.40 (2
C), 121.16, 116.21, 112.94, 70.76, 67.68, 61.69.
Benzyl [2,2-Dichloro-2-nitro-1-(3-tolyl)ethyl]carbamate (3o)
White solid; yield: 77%; mp 106–108 °C.
IR (KBr): 3416, 3315, 3034, 2962, 1715, 1585, 1501, 1334, 1230,
1053 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.18–7.32 (m, 9 H), 5.97 (d,
J = 10.4 Hz, 1 H), 5.80–5.84 (m, 1 H), 5.03–5.12 (m, 2 H), 2.35 (s,
3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C23H20Cl2N2O5Na: 497.0641;
found: 497.0642.
13C NMR (75 MHz, CDCl3): d = 154.96, 138.59, 135.48, 132.70,
130.63, 129.57, 128.65 (2 C), 128.53, 128.39, 125.79, 115.66,
67.98, 64.29, 21.46.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
HRMS (ESI): m/z [M + Na]+ calcd for C17H16Cl2N2NaO4: 405.0379;
found: 405.0374.
Primary Data for this article are available online at
http://www.thieme-connect.com/ejournals/toc/synthesis and can be
cited using the following DOI: 10.4125/pd0019th.
Benzyl [2,2-Dichloro-2-nitro-1-(4-tolyl)ethyl]carbamate (3p)
Colorless oil; yield: 93%.
IR (KBr): 3415, 3316, 3034, 2961, 1713, 1585, 1513, 1336, 1233,
1051 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.30–7.14 (m, 9 H), 5.97 (d,
J = 9.9 Hz, 1 H), 5.87 (d, J = 9.6 Hz, 1 H), 5.11–5.01 (m, 2 H), 2.33
(s, 3 H).
13C NMR (75 MHz, CDCl3): d = 155.02, 139.99, 135.53, 129.80,
129.47, 128.70, 128.66, 128.51, 128.37, 115.80, 67.95, 64.14,
21.23.
Acknowledgment
We gratefully acknowledge financial support from the National Na-
tural Science Foundation of China (No. 21102071) and the Funda-
mental Research Funds for the Central Universities (No.
1107020522 and No. 1082020502). Y.P. also acknowledges the
support of the Jiangsu 333 program.
HRMS (ESI): m/z [M + Na]+ calcd for C17H16Cl2N2NaO4: 405.0379;
found: 405.0381.
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Synthesis 2011, No. 22, 3680–3686 © Thieme Stuttgart · New York

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Synthesis 2011, No. 22, 3680–3686 © Thieme Stuttgart · New York