KI-catalyzed aminobromination of olefins with TsNH2-NBS combination

Article abstract of DOI:10.1039/b904789a

An efficient KI-catalyzed aminobromination of olefins has been developed with good to excellent yields and high regio- and stereoselectivities under transition metal-free conditions. A series of olefins, including α,β-unsaturated carbonyl compounds and simple olefins, was studied. The reaction was performed in CH₂Cl₂ using KI as the catalyst and TsNH₂ and NBS as the nitrogen and bromine sources. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b904789a

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www.rsc.org/obc | Organic & Biomolecular Chemistry
KI-catalyzed aminobromination of olefins with TsNH2–NBS combination†
Jun-fa Wei,* Li-hui Zhang, Zhan-guo Chen, Xian-ying Shi and Jing-jing Cao
Received 9th March 2009, Accepted 26th May 2009
First published as an Advance Article on the web 24th June 2009
DOI: 10.1039/b904789a
An efficient KI-catalyzed aminobromination of olefins has been developed with good to excellent yields
and high regio- and stereoselectivities under transition metal-free conditions. A series of olefins,
including a,b-unsaturated carbonyl compounds and simple olefins, was studied. The reaction was
performed in CH2Cl2 using KI as the catalyst and TsNH2 and NBS as the nitrogen and bromine sources.
necessitates the use of up to 50 (or 75) mol% of the expensive
hypervalent iodine. Aminochlorination in the presence of CO2
Introduction
seems an attractive protocol12, but the use of high pressure and
the poor substrate scope would limit its applications. Therefore,
the development of more effective and non-toxic catalysts for this
transformation is highly desirable.
Aminohalogenation of unsaturated carbon–carbon bonds rep-
resents an important difunctionalization reaction for the trans-
formation of olefins to vicinal haloamine derivatives, which are
versatile synthetic intermediates for the synthesis of functional
materials and biologically active compounds, such as aziridines,
amino alcohols, amino aldehydes and lactams, by replacement
of halogen with multifarious nucleophiles.1–4 Since several new
methodologies for the aminohalogenation of olefins have been
developed by Li and co-workers5 and others6, the preparation of
vicinal haloamine derivative has become more accessible through
the direct difunctionalization of olefins. However, despite substan-
tial improvements in recent years, significant limitations still exist,
such as procedural difficulties (including temperature control, the
need for inert atmosphere protection, unsuitability for one-pot
operation and so on), high catalyst loading, and, in particular,
the need for a variety of heavy or transition metals as catalysts.
The last mentioned shortcoming limits the attractiveness of these
methods in some cases such as the preparation of pharmaceuticals.
One of the most important uses of aminohalogenation in organic
syntheses is in the preparation of pharmaceutical products.7
In general, residual metals in pharmaceutical products (and
electronic organics) are strictly controlled to rather low levels, but
the removal of residual metals from the products is quite difficult.8
Very recently, a few reports concerning transition metal-free
aminohalogenation reactions have emerged in the literature.
For example, Li and co-workers reported an aminochlorination
of chalcones with 2-NsNCl2 in a large quantity of expensive
ionic liquid with high stereoselectivity (1:5 to one isomer), in
which the substrate range was relatively narrow and in order
to achieve a good chemical yield a higher temperature (80 ◦C)
was required.9 The aminochlorination of electron-deficient olefins
with Chloramine-T in water promoted by sulfuric acid was
also reported;10 however, the use of 1.2 equiv. of sulfuric acid
would lead to problems of acidic wastewater disposal. Amino-
bromination of olefins mediated by PhI(OAc)2 under mechanical
milling conditions11 is quite convenient, however, this protocol
We are interested in exploring more efficient and benign
methodologies for the difunctionalization of olefins. During our
endeavors to seek new catalytic methods of aminohalogenation, we
found KI and NaI to be two efficient alternative catalysts for this
transformation. Compared to heavy metal catalysts, KI and NaI
are easily removed from the reaction products by simple extraction
and water washing, and this protocol should be particularly
suitable for the synthesis of vicinal bromoamines with substrates
sensitive to acids including Lewis and Brønsted acids. Herein
we wish to describe a KI-catalyzed aminobromination of a,b-
unsaturated carbonyl compounds and simple olefins with the
TsNH2–NBS combination.13
Results and discussion
In our initial experiments, we used 1,3-diphenylpropen-1-one
as the prototypical substrate for discovery of suitable reaction
conditions and examination of the activities of the catalysts. All of
the reactions were carried out by stirring at room temperature a
mixture of the catalyst, chalcone, NBS and TsNH2 in commercial
and not degassed CH2Cl2 under aerobic conditions (Table 1).
As can be seen, both KI and NaI were found to catalyze
the aminobromination reactions, and the former was slightly
more effective. With only 1 mol% of KI, the reaction proceeded
successfully to give the desired product in a 70.3% yield. I2 gave
inferior results (28% yield), excluding I2 as the actual catalytic
species in the reaction. Considering KI is cheaper and more
effective than NaI and Bu4NI, we chose KI as the catalyst for
screening solvents and the suitable amount of catalyst. Among
the solvents screened, the use of CH2Cl2 gave the best results. A
higher loading of KI improved the yield insignificantly.
The optimized reaction conditions, 1 mol% KI, 1.0 equiv. of
TsNH2, and 1.2 equiv. of NBS in CH2Cl2 at room temperature,
were applied to the aminobromination of a number of functional-
ized a,b-unsaturated ketones and cinnamic esters. The results are
summarized in Table 2.
School of Chemistry and Materials Science, Shaanxi Normal University,
Xi’an, 710062, P. R. China. E-mail: weijf@snnu.edu.cn.; Fax: +086-029-
85307774; Tel: +086-029-85303734
† Electronic supplementary information (ESI) available: 1H and 13C NMR
spectra; X-ray structure for 31b. CCDC reference number 723422. For
ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/b904789a
Drastic differences in both reactivity and regioselectivity of
the reactions was observed between the substrates with and
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Table 1 Aminobromination of chalcone promoted by various iodides in
the aminobromination substantially, affording products in high
yields (2a–6a) within a shortened reaction time. The substrates
possessing a strong electron-withdrawing group located para to
the double bond, however, gave rather low yields (9a–11a) and
were accompanied by dibrominated product, i.e., 1-phenyl-3-
(2,3-dibromo-4-nitrophenyl)propan-1-one (9e, see ESI†). Notably,
these substrates did not proceed with the aminobromination in
cases where Cu powder14 was the catalyst. When there was no
substituent incorporated para to the double bond (R3 = Ph),
moderate yields were obtained and were influenced insignificantly
by the group on the benzene ring para to the carbonyl (1a,
11a–13a). Reactions in which a weak electron-withdrawing group
such as halogen was incorporated para to the double bond
underwent reaction with a slightly lower yield (14a–16a).
Notice that OCH3 on a benzene ring does not always promote
the aminobromination of chalcones; when one or two OCH3 were
positioned meta to the double bond (7a, 8a), electrophilic aromatic
substitution reaction on the benzene ring (7d–8d) took place
instead of the addition reaction on the double bond, probably
owning to the activation by OCH3 of the benzene ring.15
different solventsa
Loading
(mol %)
Entry
Catalyst
Solvent
Temp./◦C
Yieldb (%)
1
2
3
4
5
6
7
8
9
KI
1
1
1
1
1
1
1
1
3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
DMF
25
25
25
25
25
25
25
25
25
25
70.3
68.1
62.4
29.0
48.2
37.5
43.4
45.8
70.5
71.3
NaI
Bu4NI
I2
KI
KI
KI
KI
KI
KI
THF
Dioxane
CH2Cl2
CH2Cl2
10
10
a Conditions: chalcone (5.0 mmol), TsNH2 (5.0 mmol), NBS (6.0 mmol),
solvent 10 mL, 25 ◦C, 24 h. b Isolated yield by chromatography; no syn-
products were detected.
With aromatic enones as the starting olefins (17a–19a),
the reaction proceeded well to give the aminobromo ketones
(17c–19c) with excellent isolated yields.
Table 2 KI-catalyzed aminobromination of a,b-unsaturated ketones
with TsNH2 and NBSa
The substituents on the phenyl ring of the cinnamates also
influence the reaction remarkably (20a–25a, Table 2). An electron-
withdrawing group incorporated para to the double bond reduces
the yield. For example, ethyl 4-chlorocinnamate (25a) generated
a lower yield than ethyl cinnamate (21a). However, electron-
donating groups increase the yields, as seen by comparing 22a
and 23a with 20a, 21a, and 25a. Interestingly, in these cases the
regioselectivities were reversed (22a and 23a), consistent with those
observed in the reactions of a,b-unsaturated ketones. It is also
interesting that the alkyl group of the cinnamates influences the
reaction remarkably; methyl cinnamates are clearly more reactive
than their ethyl analogues (comparing 20a with 21a and 22a with
23a), presumably due to less hindrance from the methyl group.
With ethyl or butyl acrylate as the starting olefin, the reaction
did not occur, indicating that the aryl attached to the double bond
plays a crucial role in the aminobrominations of a,b-unsaturated
esters.
The utility of the protocol was further demonstrated using
several simple olefins under our reaction conditions. Table 3
presents six examples with yields ranging from 54–92%. All styrene
type olefins gave excellent yields of aminobromo products in which
the amine functionality was generally introduced at the benzylic
position (Table 3, entries 1–3). Moderate yields were found for
cyclic and acyclic alkenes (entries 4–6).
The stereochemical outcome indicates that the KI-catalyzed
aminobromination was stereoselective and gave exclusively vicinal
haloamine derivatives with a trans relative stereochemistry. More
importantly, two opposite regioselectivities were found for the
present protocol, dependent on whether an OCH3 group was
incorporated para to the double bond of the a,b-unsaturated
carbonyl compounds or not. In the reactions of the substrates
without a 4-methoxy group, the amine and bromine functionalities
were selectively introduced at the a- and b-positions respectively,
with a trans relative relationship (Table 2, 1b, 9b–16b, 20b, 21b,
and 25b). The substrates bearing an OCH3 group incorporated
para to the double bond resulted exclusively in the trans products
Sub. R3
R4
Prod. Yieldb (%) Time (h)
1a
2a
3a
4a
5a
6a
7a
8a
9a
Ph
Ph
Ph
4¢-ClC6H4
1b
2c
3c
70
90
98
98
97
78
93
89
43
24
1
2
1
2
24
1
1
24
24
24
24
24
24
24
24
1
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
3,4,5-(MeO)3C6H2
3,5-(MeO)2C6H3
3-MeOC6H4
4-NO2C6H4
4¢-NO2C6H4 4c
4¢-MeOC6H4 5c
4¢-NO2C6H4 6c
Ph
7dc
4¢-MeOC6H4 8dc
Ph
9b
10b 34
10a 4-NO2C6H4
4¢-ClC6H4
11a Ph
4¢-NO2C6H4 11b 68
4¢-MeOC6H4 12b 62
12a Ph
13a Ph
4¢-ClC6H4
Ph
13b 52
14b 45
14a 4-BrC6H4
15a 4-FC6H4
16a 4-FC6H4
17a 4-MeOC6H4
18a 3,4,5-(MeO)3C6H2
19a 2-Br-4,5-(MeO)2C6H2 Me
20a Ph
21a Ph
22a 4-MeOC6H4
23a 4-MeOC6H4
24a 3,4,5-(MeO)3C6H2
25a 4-ClC6H4
4¢-MeOC6H4 15b 58
4¢-ClC6H4
16b 51
Me
Me
17c
18c
19c
98
81
78
2
2
OMe
OEt
OMe
OEt
OEt
OEt
OEt
OBu-n
20b 76
21b 69
24
24
3
5
5
24
24
24
22c
23c
24c
92
81
72
25b 55
26a
27a
H
H
–
–
NR
NR
a Conditions: a,b-unsaturated compounds (5.0 mmol), TsNH2 (5.0 mmol),
NBS (6.0 mmol), catalyst (1 mol % KI), CH2Cl2 10 mL, 25 ◦C. b Isolated
yield by chromatography; no syn-products were detected. c Aromatic
substitution product.
without a strong electron-donating group incorporated para to
the double bond. The presence of a strong electron-donating
group on the benzene ring para to the double bond facilitated
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Table 3 KI-catalyzed aminobromination of simple olefins with TsNH2
and NBSa
Entry
1
Olefin
Product
Time (h)
24
Yieldb (%)
91
2
3
24
3
90
92
4
5
24
24
54
87
6
24
64
a Conditions: olefin (5.0 mmol), ◦TsNH2 (5.0 mmol), NBS (6.0 mmol),
KI (1 mol%), CH2Cl2 10 mL, 25 C. b Isolated yield by chromatography,
average of at least two experiments; no syn-products were detected.
Fig. 1 Molecular (top) and packing (bottom) structure of 31b.
with a reversed regioselectivity wherein the amine functionality
added at the b-position and bromo at the a-position (Table 2,
2c–6c, 17c–19c, and 22c–24c), as evident by MS analysis in which
the prominent fragmented ions, [R3CHNHTs]+ and [R4CO]+, were
presented. This result implies that when an OCH3 substituent on
the benzene ring is incorporated para to the double bond, not only
are the yields improved remarkably but the regioselectivities are
also reversed. Clearly the electronic effects arising from the strong
electron-donating group accelerate the reactions and contribute
to the reversed regioselectivity.
Simple olefins underwent the reaction in an anti manner too.
Asymmetric olefins such as styrene and indene gave the products
in which amine and bromine functionalities were selectively added
at the a- and b-positions. 1-Hexene gave the same regioselec-
tivity, as revealed by two major peaks, [C4H9CHNHTs+] and
[TsNHCHCH2Br+], in the MS spectrum. Cycloalkenes yielded
trans products. X-ray crystallographic analysis of a typical amino-
bromo product, trans-1-bromo-2-(tosylamido)cyclohexane (31b),
clearly shows that tosylamido and bromine functionalities were
added at the two carbons (C6, C7) in a trans relative relationship
(Fig. 1). Interestingly, both the amine and bromine are unusually
in axial rather than equatorial positions on the cyclohexane ring. A
possible explanation is that the formation of an eight-membered
ring via two H-bonds, O2 ◊ ◊ ◊ H–N1¢ and O2¢ ◊ ◊ ◊ H–N1, between
two molecules results in a gauche conformation around the
S1–N1 bond with a C1–S1–N1–C6 dihedral angle of 68.46◦, in
which the benzene ring on S1 forces the cyclohexane ring on N1
to take the diaxial chair-conformation. This tendency is further
reinforced by the benzene ring of the third molecule which accesses
the cyclohexane ring.
We have no definitive hypothesis for the exact mechanism and
the role of iodide in the reaction at the moment, however the
following observations suggest a possible bridged bromonium
mechanism in the present catalytic process: (i) the reaction
proceeded with high anti stereochemistry; (ii) in some cases,
the dibromides were obtained in considerable yields; (iii) the
reaction has an electrophilic feature as the electron-rich olefins
were drastically more reactive than the electron-poor ones; (iv)
electrophilic aromatic substitution reaction occurred in some
cases. This last mentioned observation is clear evidence of positive
bromine in the reaction.
Conclusions
In summary, we have developed a transition and heavy metal-
free catalytic method at ambient conditions for the preparation of
1,2-aminobrominated products in preparative yield and excellent
regio- and stereoselectivities from a variety of olefins, including
a,b-unsaturated carbonyl compounds and simple olefins. Con-
trary to the previous procedures, this method utilizes commercially
available KI as the aminobromination catalyst, and represents
a useful, inexpensive, and benign method, with the advantage
of needing no hazardous metals as the catalyst. In view of its
simplicity and the mild conditions, the present protocol provides
versatile and convenient access to vicinal haloamines under mild
conditions while obviating the need for heavy metal catalysts that
are frequently difficult to remove from the reaction products. The
role of KI in the reaction remains to be explored further, and
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efforts to extend the scope of this process to other synthetically
useful substrates are currently underway.
48.6, 20.8; Elemental analysis: C22H19BrN2O5S requires C, 52.49;
H, 3.80; N, 5.57 found: C, 52.51; H, 3.42; N, 5.51.
2,3-Dibromo-3-(4-nitrophenyl)-1-phenylpropan-1-one
(9e).
mp: 148–150 ◦C (EtOH) The title compound was obtained
according to the general procedure from 9a (1.27 g, 5 mmol)
with◦in 24 hours as a white solid 9e 0.62 g (30% yield); mp: 148–
150 C (EtOH) [and 9b 1.08 g (43% yield)];1H NMR (300 MHz,
CDCl3) d (ppm) 8.31 (d, J = 8.12 Hz, 2H), 8.11 (d, J = 7.69 Hz,
2H), 7.83–7.55 (m, 5H), 5.80–5.65 (t, 2H); 13C NMR (75.45 MHz,
CDCl3) d (ppm) 189.9, 147.7, 144.7, 133.9, 133.6, 128.98, 128.89,
128.6 (2), 128.4 (2), 123.6, 123.5, 46.7, 45.4; Elemental analysis:
C15H11Br2NO3 requires C, 43.62; H, 2.68 N, 3.39 found: C, 43.71;
H, 2.66; N, 3.30.
Experimental
General information
Unless otherwise stated, all reagents were purchased from com-
mercial sources and used without further purification. Reaction
progress was monitored by TLC using Merck silica gel 60 F-
254 with detection by UV or concentrated sulfuric acid as
chromogenic reagent. Flash chromatography was performed using
Merck silica gel 60 with freshly distilled solvents. Columns were
typically packed as slurry and equilibrated with the appropriate
solvent system prior to use. 1H NMR (300 MHz) and 13C
NMR (75.45 MHz) spectra were recorded on Bruker Avance
spectrometers using TMS as an internal standard. Data are
presented as follows: chemical shift (ppm), multiplicity (s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet b = broad),
coupling constant J (Hz) and integration. Elemental analysis
was carried on a PE-2400CHN (U.S) analyzer. Melting points
were uncorrected. The crystal structure was recorded on Bruker
APEX II CCD area-detector X-ray diffraction spectrometer. Mass
data were obtained with a GCMS-QP2010nc Plus mass spectro-
meter (EI).
3-Bromo-1-(4-chlorophenyl)-3-(4-nitrophenyl)-2-(tosylamino)-
propan-1-one (10b). mp: 185–186 ◦C (EtOH); 1H NMR
(300 MHz, CDCl3) d (ppm) 8.05 (d, J = 8.43 Hz, 2H), 7.85 (d,
J = 8.25 Hz, 2H), 7.49–7.35 (m, H), 6.99 (d, J = 7.62 Hz, 2H),
5.77 (d, J = 9.81 Hz, 1H), 5.45 (t, 1H), 5.06 (d, J = 9.81 Hz, 1H),
2.27 (s, 3H);13C NMR (75.45 MHz, CDCl3) d (ppm) 195.5, 147.4,
143.7, 143.2, 140.8, 136.0, 132.9, 129.9 (2), 129.1 (2), 128.9 (2),
128.7 (2), 126.4 (2), 123.2 (2), 59.2, 48.2, 20.8; Elemental analysis:
C22H18BrClN2O5S requires C, 49.13; H, 3.37; N, 5.21 found: C,
49.22; H, 3.39; N, 5.08.
3-Bromo-1-(4-nitrophenyl)-3-phenyl-2-(tosylamino)propan-1-
one (11b). mp: 183–184 ◦C (EtOH); 1H NMR (300 MHz, CDCl3)
d (ppm) 8.26 (d, J = 8.37 Hz, 2H), 8.00 (d, J = 8.22 Hz, 2H), 7.41
(d, J = 7.74 Hz, 2H), 7.32 (t, 3H), 7.04 (d, J = 7.59 Hz, 2H),
5.71 (d, J = 9.57 Hz 1H), 5.48 (t, 1H), 5.07 (d, J = 8.34 Hz, 1H),
2.29 (s, 3H);13C NMR (75.45 MHz, CDCl3) d (ppm) 196.1, 150.1,
143.4, 139.5, 136.0, 135.8, 129.4 (2), 129.1 (2), 128.7, 128.3 (2),
127.9 (2), 126.6 (2), 123.2 (2), 60.0, 50.9 20.9; Elemental analysis:
C22H19BrN2O5S requires C, 52.49; H, 3.80; N, 5.57 found: C, 52.62;
H, 3.78; N, 5.38.
General experimental procedure
A mixture of olefins (5 mmol), TsNH2 (0.86 g, 5 mmol), NBS
(1.07 g, 6 mmol) and KI catalyst (1 mol%), was taken in
CH2Cl2 (10 mL) with stirring at room temperature under aerobic
conditions. The reaction was monitored by TLC. After completion
of the reaction, it was diluted with EtOAc (20 mL) and washed with
water (3 ¥ 15 mL) and brine (3 ¥ 15 mL). The organic layer was
dried over anhydrous Na2SO4 and concentrated under reduced
pressure to give crude product, which was purified by column
chromatography packed with silica gel using petroleum ether–
ethyl acetate as eluents to afford pure product.
The identities of known compounds 1b, 2c–6c, 7d, 12b–13b, 15b,
17c–19c, 20b, 23c, 25b, 28b, 30b–33b were confirmed by compari-
son of their spectral data with the reported ones.13a,14 Physical and
spectroscopic data of the others synthesized compounds are given
below.
3-Bromo-3-(4-bromopheny)-1-phenyl-2-(tosylamino)propan-1-
one (14b). mp: 170–172 ◦C (EtOH); 1H NMR (300 MHz, CDCl3)
d (ppm) 7.86 (d, J = 7.47 Hz, 2H), 7.65 (m, 1H), 7.52–7.26 (m,
6H), 7.04 (d, J = 7.5 Hz, 2H), 5.55–5.44 (m, 2H), 5.01 (d, J =
7.05 Hz, 1H), 2.30 (s, 3H);13C NMR (75.45 MHz, CDCl3) d (ppm)
196.1, 143.2, 136.2, 135.3, 134.6, 133.8, 131.2 (2), 129.6 (2), 128.9
(2), 128.4 (2), 128.3 (2), 126.5 (2), 122.7, 59.9, 49.8, 20.9; Elemental
analysis: C22H19Br2NO3S requires C, 49.18; H, 3.56; N, 2.61 found:
C, 49.31; H, 3.44; N, 2.55.
3-(4-Bromo-3-meth◦oxylphenyl)-1-(4-methoxyphenyl) allylketone
1
(8d). mp: 127–128 C (EtOH); H NMR (300 MHz, CDCl3)
3-Bromo-1-(4-chlorophenyl)-3-(4-fluoropheny)-2-(tosylamino)-
propan-1-one (16b). mp: 140–141 ◦C (EtOH); 1H NMR
(300 MHz, CDCl3) d (ppm) 7.78 (d, J = 8.40 Hz, 2H), 7.42–
7.39 (m, 2H), 7.11 (d, J = 7.82 Hz, 2H), 6.82–7.02 (m, 2H), 5.58
(d, J = 6.00 Hz, 1H), 5.43–5.32 (m, 1H), 4.13–4.08 (m, 1H), 2.34 (s,
3H); 13C NMR (75.45 MHz, CDCl3) d (ppm) 195.6, 163.9, 160.7,
143.3, 140.4, 136.2, 133.2, 132.1 (2), 129.9 (2), 128.96 (2), 128.86
(2), 126.5 (2), 115.3, 114.9, 59.7, 49.8, 20.8; Elemental analysis:
C22H18BrClFNO3S requires C, 51.73; H, 3.55; N, 2. 74 found: C,
51.75; H, 3.56; N, 2.76.
d (ppm) 8.06 (m, 3H), 7.40 (m, 3H), 6.99 (d, J = 8.52 Hz,
2H), 6.84–6.80 (m, 1H), 3.89 (s, 3H), 3.85 (s, 3H); 13C NMR
(75.45 MHz, CDCl3) d 188.2, 163.1, 158.5, 141.8, 135.5, 133.5,
130.5 (2), 130.3, 124.7, 116.7, 115.9, 113.4 (2), 112.6, 55.13, 54.9;
Elemental analysis: C17H15BrO3 requires C, 58.81; H, 4.35 found:
C, 58.92; H, 4.33.
3-Bromo-3-(4-nitrophenyl)-1-phenyl-2-(tosylamino)propan-1-
one (9b). mp: 160–161◦C (EtOH); 1H NMR (300 MHz, CDCl3)
d 8.06 (d, J = 8.40 Hz, 2H), 7.88–7.85 (d, 2H), 7.77 (d, J =
7.32 Hz, 1H), 7.6–7.41 (m, 6H), 7.98 (d, J = 7.59 Hz, 2H), 5.62
(d, J = 9.69 Hz, 1H), 5.54–5.48 (m, 1H), 5.09 (d, J = 8.07 Hz,
1H), 2.25 (s, 3H); 13C NMR (75.45 MHz, CDCl3) d (ppm) 196.1,
147.4, 143.5, 143.4, 143.3, 143.2, 136.1, 134.5, 134.1, 129.2, 129.1,
128.97, 128.93, 128.7, 128.68, 128.66, 128.5, 126.4, 123.2, 59.6,
Ethyl 3-bromo-3-phenyl-2-(tosylamino)propionate (21b). mp:
◦
1
121–123 C (EtOH); H NMR (300 MHz, CDCl3) d (ppm) 7.63
(d, J = 7.8 Hz, 2H), 7.41–7.23 (m, 8H), 5.18–5.12 (m, 2H), 4.48–
4.43 (m, 1H), 3.98 (q, 2H), 2.41 (s, 3H), 1.10 (t, 3H);13C NMR
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(75.45 MHz, CDCl3) d (ppm) 168.1, 143.3, 136.1, 135.8, 129.1 (2),
128.5 (2), 128.1, 127.8 (2), 126.9 (2), 61.7, 61.4, 51.4, 20.9, 13.3;
Elemental analysis: C18H20BrNO4S requires C, 50.71; H, 4.73; N,
3.29 found C, 50.75; H, 4.74; N, 3.30.
Shaanxi Province (2006B20), and the Innovation Foundation of
Postgraduate Cultivation of Shaanxi Normal University.
References
Methyl 2-bromo-3-(4-methoxyphenyl)-3-(tosylamino)propionate
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◦
1
(22c). mp: 90–91 C (EtOH); H NMR (300 MHz,CDCl3) d
(ppm) 7.56 (d, J = 7.95 Hz, 2H), 7.25 (d, J = 5.52 Hz, 2H), 7.12
(d, J = 7.59 Hz, 2H), 7.02 (d, J = 8.37 Hz, 2H), 6.69 (d, J =
8.37 Hz, 2H), 6.19 (d, J = 9.15 Hz, 1H), 4.85–4.83 (m, 1H), 4.45
(d, J = 5.76 Hz, 1H), 3.74 (s, 3H), 3.65 (s, 3H), 2.35 (s, 3H);13C
NMR (75.45 MHz, CDCl3) d (ppm) 168.2, 159.1, 142.6, 137.1 (2),
128.7 (2), 127.7 (2), 126.7 (2), 113.5 (2), 59.1, 54.7, 52.6, 46.3, 20.9;
Elemental analysis: C18H20BrNO5S requires C, 48.88; H, 4.56; N,
3.17 found: C, 49.01; H, 4.50; N, 3.00.
Ethyl
2-bromo-3-(3,4,5-trimethoxyphenyl)-3-(tosylamino)-
propionate (24c). mp: 144–145 ◦C (EtOH); 1H NMR (300 MHz,
CDCl3) d (ppm) 7.56 (d, J = 7.89 Hz, 2H), 7.12 (d, J = 7.77 Hz,
2H), 6.46 (d, J = 9.03 Hz, 1H), 6.28 (s, 2H), 4.82 (m, 1H), 4.45
(d, J = 6.00 Hz, 1H), 4.16 (q, 2H), 3.77 (s, 9H), 2.33 (s, 3H),
1.23 (t, 3H); 13C NMR (75.45 MHz, CDCl3) d (ppm) 167.9,
152.6 (2), 142.7, 137.4, 137.1, 132.1, 131.3, 128.6 (2), 126.6 (2),
104.9, 103.8, 62.0, 60.2, 60.0, 55.5, 46.1, 20.8; Elemental analysis:
C21H26BrNO7S requires C, 48.84; H, 5.07; N, 2.71 found: C, 48.87;
H, 5.00; N, 2.63.
1-Bromo-1,2-diphenyl-2-(tosylamino)ethane (29b). mp: 159–
◦
1
160 C (EtOH); H NMR (300 MHz, CDCl3) d (ppm) 7.45 (d,
J = 8.94 Hz, 2H), 7.20–7.05 (m, 10H), 6.89 (d, J = 7.29 Hz, 2H),
5.17 (m, 2H), 4.78 (m, 1H), 2.34 (s, 3H); 13C NMR (75.45 MHz,
CDCl3) d (ppm) 143.2, 136.7, 136.2, 129.3, 129.29, 129.2, 128.9,
128.7, 128.65, 128.5, 128.4, 128.3, 128.1, 128.06, 127.9, 127.8,
127.15, 127.1, 63.1, 58.3, 21.4; Elemental analysis: C21H20BrNO2S
requires C, 58.61; H, 4.68; N, 3.25 found: C, 58.63; H, 4.69; N, 3.26.
◦
1-Bromo-2-(tosylamino)hexane (33b). mp: 84–86 C (EtOH);
1H NMR (300 MHz, CDCl3) d (ppm) 7.78 (d, J = 7.88 Hz,
2H), 7.32 (d, J = 7.62 Hz, 2H), 4.70 (s, 1H), 3.41–3.30 (m, 3H),
2.43 (s, 3H), 1.55–0.78 (m, 9H);13C NMR (75.45 MHz, CDCl3) d
(ppm) 143.7, 137.8, 129.8 (2), 127.5 (2), 60.4, 38.2, 32.9, 27.3,
22.1, 21.5, 14.2; MS m/z (% rel. intensity): 334 (M+, 8), 240
(50)C4H9CH(NHTs); Elemental analysis: C13H20BrNO2S requires
C, 46.71; H, 6.03; N, 4.19 found: C, 46.72; H, 6.04; N, 4.21.
Crystal data for 31b. C13H18BrNO2S M = 332.25, Triclinic,
˚
space group P1, a = 7.0140(14), b = 9.4940(19), c = 11.755(2) A,
3
˚
a = 74.26(3), b = 79.41(3), g = 86.75(3), V = 740.6(3) A , T =
˚
293(2) K, Z = 2, m-(Mo-Ka) = 0.71073 A, colourless block, crystal
dimensions 0.12 ¥ 0.10 ¥ 0.08 mm, crystal density 1.490. Full
matrix least squares based on F2 gave R1 = 0.0625 and wR2 =
0.1679 for 2730 (I ≥2s(I)), GOF = 0.998 for 168 parameters.
13 For selected examples on aminobromination of olefin with TsNH2
and NBS as the nitrogen and bromine sources, see: (a) V. V. Thakur,
S. K. Talluri and A. Sudalai, Org. Lett, 2003, 5, 861; (b) D. Chen, C.
Timmons, S. Chao and G. Li, Eur. J. Chem., 2004, 3097; (c) X. Huang
and W-J. Fu, synthesis, 2006, 1016.
14 Z.-G. Chen, J.-F. Wei, R.-T. Li, X.-Y. Shi and P.-F. Zhao, J. Org. Chem.,
2009, 74, 1371.
Acknowledgements
The authors are grateful to the National Foundation of Natural
Science (Grant No.20572066), the Natural Science Foundation of
15 R. Rajagopal, D. V. Jarikote, R. J. Lahoti, T. Daniel and K. V.
Srinivasan, Tetrahedron Lett., 2003, 44, 1815.
3284 | Org. Biomol. Chem., 2009, 7, 3280–3284
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The Royal Society of Chemistry 2009
©