Silicon powder: The first nonmetal elemental catalyst for aminobromination of olefins with TsNH2 and NBS

Article abstract of DOI:10.1021/ol9015833

Silicon powder was found, for the first time, to be an efficient alternative to transition metal catalysts for aminobromination of α,β-unsaturated carbonyl compounds and simple olefins with p-toluenesulfonamide (4-TsNH₂) and NBS, affording the

Full text of DOI:10.1021/ol9015833

ORGANIC
LETTERS
2009
Vol. 11, No. 18
4216-4219
Silicon Powder: The First Nonmetal
Elemental Catalyst for
Aminobromination of Olefins with TsNH2
and NBS
Jun-Fa Wei,*,† Zhan-Guo Chen,† Wei Lei,† Li-Hui Zhang,† Ming-Zheng Wang,†
Xian-Ying Shi,† and Run-Tao Li‡
School of Chemistry and Materials Science, Shaanxi Normal UniVersity, Shaanxi Xi’an
710062, P. R. China, and School of Pharmaceutical Sciences, Peking UniVersity,
Beijing 100083, P. R. China
weijf@snnu.edu.cn
Received July 11, 2009
ABSTRACT
Silicon powder was found, for the first time, to be an efficient alternative to transition metal catalysts for aminobromination of r,ꢀ-unsaturated
carbonyl compounds and simple olefins with p-toluenesulfonamide (4-TsNH2) and NBS, affording the aminobrominated products in high yields
and regio- and stereoselectivity. The high reactivity of electron-rich substrates reveals that the reaction has the electrophilic addition feature.
Aminohalogenations of olefinic double bonds have gained
great interest recently, and they constitute a synthetic tool
to prepare the vicinal haloamino functionality.1-6 These
reactions generally proceeded with transition metal salts or
their complexes as catalysts, such as CuI, CuCl2·2H2O,
CuCN, Cu(OAc)2, CuOTf, V2O5, MnSO4, Mn(III)-salen,
FeCl3-PPh3, Co(OAc)2·4H2O, NiCl2·6H2O, ZnCl2, LPdCl2
(L ) 1,10-phenanthroline), [(C3F7CO2)2Rh]2, Pd/C, and so
on.7,8 Very recently, we have reported that copper powder
promotes the aminobromination of R,ꢀ-unsaturated ketones
with NBS and TsNH2 as the nitrogen/bromine sources.9
However, the use of transition metals or related ligands is
generally limited for certain applications since the acceptable
level of transition metal residuals is highly regulated in
certain products, especially pharmaceutics and the removal
of metal impurities is a challenging issue. Although a few
noncatalyzed addition reactions have been reported10 and
several transition- or heavy-metal-free aminohalogenations
† Shaanxi Normal University.
‡ Peking University.
(1) (a) Kemp, J. E. G. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, U.K., 1991; Vol. 3, pp 471-513. (b)
Li, G.; Kotti, S. R. S. S.; Timmons, C. Eur. J. Org. Chem. 2007, 2745
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(2) (a) Daniher, F. A.; Butler, P. E. J. Org. Chem. 1968, 33, 4336. (b)
Daniher, F. A.; Butler, P. E. J. Org. Chem. 1968, 33, 2637. (c) Lessard, J.;
Driguez, H.; Vermes, J.-P. Tetrahedron Lett. 1970, 11, 4887. (d) Barton,
D. H. R.; Britten-Kelly, M. R.; Ferreira, D. J. Chem. Soc., Perkin Trans.
1978, 1, 1090. (e) Driguez, H.; Vermes, J.-P.; Lessard, J. Can. J. Chem.
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10.1021/ol9015833 CCC: $40.75
Published on Web 08/14/2009
 2009 American Chemical Society

were reported recently, significant shortcomings still remain
including the need of a large quantity of ionic liquid,11a
stoichiometric PhI(OAc)2,11b a large quantity of sulfuric
acid,11c or CO2 at high pressure.11d Thus, less costly, metal-
free, and operationally simple aminobromination methods
for obtaining aminobromo products from olefins are desir-
able.
Table 1. Catalytic Activity of Various Nonmetallic Elemental
Substances in the Aminobromination of Chalconea
entry
catalyst
amount (mol %)
yield (%)b
1
2
3
4
5
6
7
8
9
no catalyst
B
Si
Si
Si
Ge
P
S
Se
I2
0
1
10
5
1
1
1
1
1
1
23
73
75
74
74
19
10
NR
45
30
NR
18
In our continuous efforts to seek more benign catalysts
for difunctionalzations of carbon-carbon double bonds, we
found recently that elemental silicon powder is an efficient
yet still low-priced, comparatively nontoxic, metal- and
ligand-free catalyst for aminobrominations. The reactions
were carried out smoothly at room temperature in good to
excellent yields of the desired products. We herein wish to
report the use of elemental silicon powder as the catalyst
for aminobromination of carbon-carbon double bonds
including R,ꢀ-unsaturated ketones, cinnamic esters, and
simple alkenes with a TsNH2-NBS system. No report
involving the use of elemental silicon as a catalyst in organic
reactions was found in SCIfinder, though silicon is well-
known as a semiconductor and wafer material.
10
11
12
Br2
SiCl4
1
1
a Conditions: chalcone (5 mmol), TsNH2 (5 mmol), NBS (6 mmol),
silicon powder (amounts used in 1-10 mol %), CH2Cl2 (10 mL), 25 °C.
b Isolated yield after chromatographic separation.
The scope and limitation of the silicon-powder-catalyzed
aminobromination were investigated by various olefins such
as R,ꢀ-unsaturated ketones and cinnamic esters (Table 2).
The results show that the silicon-catalyzed aminobromination
was influenced remarkably by the substituents and their
positions at the phenyl rings, in particular, the phenyl ring
linked to the carbon-carbon double bond, similar to the
observations in our copper-powder-catalyzed reaction re-
ported previously.9 Entries 1a-4a indicate that a strong
electron-donating group (e.g., OCH3) incorporated para to
the double bond facilitated the reaction extraordinarily and
gave the trans addition products as the sole products in nearly
quantitative yields, regardless of the nature of the substituents
on another phenyl linked to carbonyl group (entries 1a-4a).
In sharp contrast to the chalcones with an OCH3 para to the
double bond, the reaction was prohibited completely with
the substrates having a strong electron-withdrawing group
(NO2) at the same position. In this case, the reaction failed
even though there is a strong electron-donating group (OCH3)
present at 4′-position and reaction time was prolonged to
48 h (entries 5a and 6a).
Methoxy present at the 4′-position of benzene ring
conjugated to the carbonyl group deactivates the reaction
significantly in the absence of a 4-substituent (compare 8a
with 7a and 9a). However, 4′-OCH3 is able to activate the
chalcones that have a weak electron-withdrawing group such
as flouro at the 4-position (compare 11a with 10a and 12a).
Notably, with 4-flouro-4′-chlorochalcone (12a) as starting
olefin, silicon powder also worked, whereas it failed to afford
the aminobrominated product when copper powder was used
as catalyst.9 Multisubstituted cholcones with 4-methoxy also
afforded the desired addition products in good to excellent
yields (13b-14b, 83-98%).
Our initial experiments focused on examining the catalytic
activity of silicon powder and other nonmetal elements in
the aminobromination of R,ꢀ-unsaturated ketone by using
chalcone (1,3-diphenyl-propen-1-one), chosen because of its
simplicity and moderate reactivity to the reaction. The
reaction was carried out by stirring at room temperature a
mixture of catalyst, chalcone, NBS, and TsNH2 in CH2Cl2
under the common conditions reported previously in
literature,7b except for an inert atmosphere. The results are
summarized in Table 1.
As shown in Table 1, silicon powder is an efficient catalyst
for the aminobromination of chalcone at ambient conditions
(entries 3-5). Even a 1 mol % loading (entry 5) is sufficient
for a smooth reaction, affording the desired product in a
slightly higher yield compared with the literature using Cu(I)
salts as catalyst.7b,c Beyond these advantages it is particularly
noteworthy that at the end of the reaction the catalyst can
be removed by simple filtration. Furthermore, the silicon
powder can be reused four times with no reduction in the
yields of corresponding addition products. It is worthy to
point out that because of low toxicity, low cost, recyclability,
and simple separation of silicon from the reaction mixture,
our method had green and economical advantages over other
metallic catalysts.
Several other potential catalysts of nonmetals were tested,
and the results indicated that boron powder was another
effective catalyst (entry 2, 73% yield). However, selenium,
phosphorus, and molecular iodine are less reactive (entries
7, 9, and 10); sulfur and bromine (entry 8 and 11) failed to
give any aminobromo product.
(10) (a) Chen, D.; Timmons, C.; Wei, H.-X.; Li, G. J. Org. Chem. 2003,
68, 5742. (b) Timmons, C.; Chen, D.; Xu, X.; Li, G. Eur. J. Org. Chem.
2003, 3850.
It is noteworthy that when OCH3 was incorporated meta
to the double bond, electrophilic aromatic substitution other
than the addition reaction on the double bond occurred.
3-Methoxy and 3,5-dimethoxy chalcones afforded the cor-
responding 4-bromo chalcones as the sole products in high
(11) (a) Wang, Y.-N.; Ni, B.; Headley, A. D.; Li, G. AdV. Synth. Catal.
2007, 349, 319. (b) Wu, X.-L.; Xia, J-J; Wang, G.-W. Org. Biomol. Chem.
2008, 6, 548. (c) Wu, X.-L.; Wang, G.-W. J. Org. Chem. 2007, 72, 9398.
(d) Minakata, S.; Yoneda, Y.; Oderaotoshi, Y.; Komatsu, M. Org. Lett.
2006, 8, 967.
Org. Lett., Vol. 11, No. 18, 2009
4217

Table 2. Silicon-Powder-Catalyzed Aminobromiation of Various R,ꢀ-Unsaturated Carbonyl Compoundsa
entry
R1
R2
product
yield (%)b
anti:syn (%)c
time (h)
mp (°C)
1a
2a
3a
4a
5a
6a
7a
8a
9a
10a
11a
12a
13a
14a
15a
16a
17a
18a
19a
20a
21a
22a
23a
24a
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-NO2C6H4
4-NO2C6H4
C6H5
C6H5
C6H5
4-FC6H4
4-FC6H4
C6H5
1b
2b
3b
4b
91
98
96
98
NRe
NR
75
27
26
13
60
32
83
98
90
91
98
82
77
65
25
78
65
NR
>95
>95
>95
>95
24
1
2
155-156
175
162-163
156-157
4′-CH3OC6H4
4′-ClC6H4
4′-NO2C6H4
C6H5
4′-CH3OC6H4
C6H5
4′-CH3OC6H4
4′-ClC6H4
C6H5
4′-CH3OC6H4
4′-ClC6H4
C6H5
C6H5
C6H5
4′-CH3OC6H4
C6H5
CH3
1
48
48
9
24
26
48
24
48
1
7c
8c
9c
>95
>95
>95
>95
>95
>95
>95
>95
124-126
159-159.5
139-140
150-151
164-165
140-141
167-168
152-153
59-60
10c
11c
12c
13b
14b
15dd
16c
17dd
18b
19b
20b
21c
22b
23b
4-FC6H4
3,4,5-(CH3O)3C6H2
2-Br-4,5-(CH3O)2C6H2
3-CH3OC6H4
3-CH3OC6H4
3,5-(CH3O)2C6H3
4-CH3OC6H4
2-Br-4,5-(CH3O)2C6H2
3,4,5-(MeO)3C6H2
C6H5
24
24
2
2
1
>95
182-184
174-175
93-95
>95
>95
>95
>95
>95
>95
CH3
CH3
OC2H5
OC2H5
OC2H5
OC2H5
88-90
3
177-179
121-123
118-119
137-139
24
24
3
4-CH3OC6H4
3,4,5-(MeO)3C6H2
H
a Conditions: R,ꢀ-unsaturated carbonyl compound (5.0 mmol), TsNH2 (5.0 mmol), NBS (6.0 mmol), silicon powder (1 mol %), CH2Cl2 10 mL, 25 °C.
c
b Isolated yield after chromatography separation. The ratio of anti:syn products, >95%, means no syn-isomer in the product mixture was detected by H
1
NMR. d Aromatic substitution product. e NR: no reaction.
yields of 90% and 98% (15d, 17d) under the same condition.
However, 3,4′-dimethoxy chalcone gave the expected addi-
tion product in high yield (16c, 91%).
oxy substituent gave the trans-R-amino-ꢀ-bromo products
alone (Table 2, 7c-12c, 16c, 21c), which are spectrally
consistent with that reported.9 X-ray crystallographic analysis
of 8c (Figure 1) showed clearly that nitrogen atom was added
to R-carbon and bromine atom to ꢀ-carbon in an anti manner.
However, a feature of the reversal in regioselectivity was
observed when the benzene ring linked to the double bond
bears a 4-OCH3 group (Table 2, 1b-4b, 13b-14b,
18b-20b, and 23b), as revealed by MS analysis that the
prominent fragment ions, [R1CHNHTs]+ and [R2CO]+,
present in the corresponding reversed products. Apart from
the MS evidence, X-ray crystallographic analysis showed
undoubtedly that 1b, derived from 4-OCH3 chalcone, has a
completely reversed regioselectivity in which nitrogen and
bromine were added to ꢀ- and R-carbon respectively in a
trans relative stereochemistry (Figure 1).
Styrene-type olefins also gave only regioselective amino-
bromo products in which the amino is at the benzylic position
and bromo is at the ꢀ-position (Table 3, entry 1 and 3).
1-Hexene gave the similar regioselective addition product
in which bromine is at the terminal carbon and nitrogen is
at the vicinal carbon, as evidenced by spectral analysis (1H
and 13C NMR) and the mp was in good agreement with that
of literature reported.6 The product was further characterized
Aromatic enones underwent the silicon-powder-catalyzed
aminobromination readily and gave the aminobromo products
in good yields (18b-20b) under the same condition. The
reaction also proceeded smoothly with R,ꢀ-unsaturated ester,
i.e., ethyl cinnamate and its 4-methoxy analog (22a, 23a) as
starting olefins; the latter is clearly more reactive and gave
the reversal in regioselective aminobromination. However,
the reaction failed with ethyl acrylate, indicating that the aryl
on the double bond plays a crucial role in the aminobromi-
nations of R,ꢀ-unsaturated esters.
The synthetic application of this protocol is also suitable
for the aminobromination of simple olefins (Table 3). The
reaction was performed successfully for cyclic and acyclic
alkenes. The corresponding chemical yields are from 85%
to 95% in the investigated examples, except for cyclohexene.
Regio- and stereoselectivity of the addition products were
determined by their melting points,1H NMR, 13C NMR, and
sometimes by MS or X-ray crystallography if possible. The
results also show that all of the addition products have a
trans relative relationship between bromo and amino groups.
The R,ꢀ-unsaturated carbonyl compounds without a 4-meth-
4218
Org. Lett., Vol. 11, No. 18, 2009

Table 3. Aminobromination of Simple Olefinsa
Figure 1. X-ray crystal structure of product 8c and 1b.
the trans-R-amino-ꢀ-bromo products obtained indicate that
aziridinium intermediate maybe present in this reaction.
In conclusion, we have found that the elemental silicon
can be used as an efficient catalyst for the aminobromination
reaction. This protocol has the advantages of a large scope
of olefins and high regio- and stereoselectivity with the NBS/
TsNH2 combination at ambient conditions. Additionally,
silicon powder as catalyst has the advantage of avoiding any
hazardous metals retained in products. The relative nontox-
icity, low cost, recyclability, and simpleness of product
isolation and silicon separation from reaction mixture make
the methodology a useful tool for preparation of the vicinal
aminobromo products, especially considering that the trace
transition metal residues are highly regulated. More impor-
tantly, this may be the first example of using elemental silicon
as catalyst in organic reactions.
a Conditions: olefins (5 mmol), TsNH2 (5 mmol), NBS (6 mmol), silicon
powder (1 mol %), CH2Cl2 (10 mL), 25 °C. b Isolated yield after
chromatographic separation.
by MS data in which [CH3(CH2)4CHNHTs]+ and
[TsNHCHCH2Br]+ appeared as two main fragment ions.
This work reveals that the activity and the regioselectivity
of the silicon-powder-catalyzed aminobromination depend
significantly on the electron density of the double bond. The
fact that electron-rich olefins are more reactive than electron-
deficent ones suggests that the aminobromination is also an
electrophilic addition reaction, as reported previously using
metallic catalysts.12-14 Although the exact mechanism of the
reaction and the role of silicon played are not clear now, the
observations of the high reactivity of electron-rich substrates,
high anti stereochemistry, formation of dibromides in some
cases, and the electrophilic aromatic substitution reaction
suggest that a possible bridged bromonium mechanism is
present. Additionally, the purely Lewis acid catalyzed
mechanism could be excluded because SiCl4 was ineffective
toward the reaction. In this case, the yield reduced to 18%,
even lower than that of the control experiment. However,
Acknowledgment. The authors are grateful to the National
Foundation of Natural Science in China (Grant No.20572066),
the Natural Science Foundation of Shaanxi Province
(2006B20), and the Innovation Foundation of Postgraduate
Cultivation of Shaaxi Normal University (2008CXB009).
Supporting Information Available: Experimental pro-
cedure, analytical and spectral data of all componds, and
X-ray crystal structure of products 8c and 1b in CIF format.
This material is available free of charge via the Internet at
http://pubs.acs.org.
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Org. Lett. 2003, 5, 3313. (b) Muniz, K.; Nieger, M. Synlett 2003, 211
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Alonso, M.; Tortosa, M.; Flores, A.; Mart´ınez-Ripoll, M.; Fonseca, I.; Andre´,
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I.; Rodr´ıguez, A. Chem.sEur. J. 2003, 9, 2867
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