Titanium superoxide: a heterogeneous catalyst for anti-Markovnikov aminobromination of olefins

Article abstract of DOI:10.1016/j.tetlet.2009.03.169

A new facile procedure for the aminobromination of olefins in high yields has been described using p-toluene sulfonamide (p-TsNH₂) and N-bromosuccinimide (NBS) as nitrogen and bromine sources, respectively, and titanium superoxide as a truly he

Full text of DOI:10.1016/j.tetlet.2009.03.169

Tetrahedron Letters 50 (2009) 2815–2817
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Tetrahedron Letters
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Titanium superoxide: a heterogeneous catalyst for anti-Markovnikov
aminobromination of olefins
*
Tanveer Mahamadali Shaikh, Pratibha U. Karabal, Gurunath Suryavanshi, Arumugam Sudalai
Chemical Engineering and Process Development Division, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008 Maharashtra, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A new facile procedure for the aminobromination of olefins in high yields has been described using p-tol-
uene sulfonamide (p-TsNH2) and N-bromosuccinimide (NBS) as nitrogen and bromine sources, respec-
tively, and titanium superoxide as a truly heterogeneous catalyst. The formation of anti-Markovnikov
product exclusively in all the cases studied possibly proceeding through a free radical reaction pathway
is remarkable.
Received 3 March 2009
Revised 20 March 2009
Accepted 26 March 2009
Available online 28 March 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Titanium superoxide
N-Bromosuccinimide
p-Toluenesulfonamide
Bromoamination
anti-Markovnikov addition
The vicinal haloamine functionality represents a useful struc-
tural moiety as well as a versatile building block in organic and
medicinal chemistry.1 In the area of synthetic organic chemistry,
these can be readily converted into a variety of useful functional
derivatives on replacement of halogen with nucleophiles in both
intramolecular and intermolecular fashion.2 Literature search
reveals that vicinal haloaminations are carried out using several
catalysts such as V2O5,3 MnSO4,3 Mn(II) salen,3 Cu-salts,4 InBr3,5
Fe-salt,6 BF3,7 SnCl4,8 Pd-complex,9 PhI(OAc)2,10 N-N-dihalosulf-
onamides,11a N-N-dihalocarbamates,11b–g N-halocarbamates11h
cyanamide-NBS11i as well as by noncatalytic routes which include
use of Bronsted acids12 such as H2SO4 or ionic liquid media
[Bmim][BF4].13 But most of these methods suffer from drawbacks
such as lack of product selectivity and use of non-economic, unsta-
ble, and toxic metals as catalysts. Hence, a search for readily avail-
able non-toxic, inexpensive and reusable catalyst is highly
desirable. In this Letter, we report that titanium superoxide14a cat-
alyzes aminobromination of olefins, which proceeds regiospecifi-
cally in an anti-Markovnikov fashion and under truly
heterogeneous conditions.
ing the course of our study on further application of titanium
superoxide in organic synthesis, we have now found that olefins
can be regiospecifically aminobrominated using p-TsNH2 and NBS
as nitrogen and bromine sources under ambient conditions. For in-
stance, when styrene was subjected to bromoamination, the corre-
sponding anti-Markovnikov product, 1, was formed in 81% yield;
whereas the commercially available TiO2, under similar conditions,
gave the expected Markovnikov product, 2 in 30% yield (Scheme 1).
Encouraged by this result, it was of interest to screen several
other titanium salts such as titanium silicalite (a zeolite), TiCl4,
and titanium isopropoxide under similar reaction conditions; the
results of which are presented in Table 1. Remarkably, titanium
superoxide gave the anti-Markovnikov product 1 in 81% yield
whereas all other titanium salts furnished the expected Markovni-
kov product, 2 with low yields. Among several solvents screened,
CH2Cl2 was found to be more suitable for titanium superoxide-cat-
alyzed aminobromination of olefins. Thus, the optimal condition
NHTs
Br
Br
Some time ago, we have reported a new method for the prepa-
ration of titanium superoxide, which was found to exist as a
remarkably stable radical at ambient conditions.15 This heteroge-
neous catalyst has been subsequently found to catalyze the selec-
tive oxidation of aromatic primary amines and phenols to the
corresponding nitro aromatics and p-quinones, respectively.15 Dur-
i
NHTs
2
1
--
30%
TiO2
--
titanium superoxide 81%
* Corresponding author. Tel.: +91 20 25902174; fax: +91 20 25902676.
E-mail address: a.sudalai@ncl.res.in (A. Sudalai).
Scheme 1. Reagents and conditions: Titanium catalyst (10 wt %), p-TsNH2
(1.1 equiv), NBS (1 equiv), CH2Cl2, 25 °C, 14 h.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.03.169

2816
T. M. Shaikh et al. / Tetrahedron Letters 50 (2009) 2815–2817
Table 1
Table 2
Titanium-catalyzed regiospecific aminobromination of styrenea
Titanium superoxide-catalyzed aminobromination of olefinsa
No
Catalyst
Solvent
Yieldb (%)
No
Substrate
Productb
Yieldc (%)
81 (58)d
anti:syn
1
2
Br
1
Styrene
NHTs
Br
1
2
3
4
5
6
7
No catalyst
TiO2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
EDC
—
—
—
—
81
61
58
17
38
23
24
—
Ph
Titanium silicalite
Ti (OPri)4
NHTs
NHTs
Titanium superoxide
Titanium superoxide
Titanium superoxide
2
3
4-Methylstyrene
86
67
—
—
H3C
Reaction conditions: aolefin (3 mmol), p-TsNH2 (3.3 mmol), N-bromosuccinimide
(3 mmol), catalyst (10 wt %), CH2Cl2 (20 mL), 25 °C, 14 h.
Br
b
4-Methoxystyrene
Isolated yield after chromatographic purification.
MeO
Br
NHTs
for the aminobromination of olefins turned out to be: olefin
(3 mmol), p-TsNH2 (3.3 mmol), NBS (3 mmol) and titanium super-
oxide (10 wt %) in CH2Cl2 at ambient conditions.
4
4-Bromostyrene
69
Br
In order to establish its scope, various olefins were subjected to
aminobromination; the results of which are presented in Table 2. It
is evident that several styrenic substrates including indene under-
went the aminobromination regiospecifically to produce the corre-
sponding anti-Markovnikov14b products. No traces of Markovnikov
products were, however, observed in the crude product sample (as
confirmed by 1H and 13C NMR and GC analysis). Interestingly, elec-
tron-rich olefins gave relatively higher yields of products as com-
pared to electron-deficient olefins. This may be ascribed to the
benzylic radical, which abruptly increases its reactivity, thereby
resulting in high yields of the aminobrominated product. Also ali-
phatic olefins underwent aminobromination smoothly to give 1,2-
bromoamines in good yields. After the reaction was complete, solid
titanium superoxide was recovered by simple filtration, which on
subsequent reuse with styrene as substrate was found to catalyze
the aminobromination process with moderate yield (58%). Notably,
substrates like indene, cyclohexene, and cyclooctene gave the cor-
responding aminobrominated products with high anti-selectivity >
99:1 (Table 2, entries 10, 12, and 13).
Cl
Br
NHTs
5
6
2-Chlorostyrene
68
78
67
30
61
80
66
65
72
63
Br
NHTs
4-Fluorostyrene
F
Br
NHTs
7
4-Chloromethylstyrene
Cl
Br
8
a-Methylstyrene
NHTs
Ph
Ph
Ph
Br
9
trans-Stilbene
Indene
Having established the aminobromination of simple olefins, we
NHTs
Br
turned our attention to
a,b-unsaturated carbonyl compounds 3a–c
as substrates and the results are presented in Table 3. For
a,b-
unsaturated esters or ketones, the reaction was found to be rela-
tively slow and gave poor yields of the expected bromoaminated
products 4a–c (Table 3, entries 1 and 2). However, use of p-TsNBr2
resulted in the formation of bromoamino ester 4c in good yield.
A plausible mechanistic pathway is outlined in Figure 1 to ex-
plain the formation of anti-Markovnikov product. Firstly, p-tolu-
enesulfonamide reacts with NBS to form p-TsNH–Br3 followed by
its interaction with titanium superoxide which facilitates the
polarization of the NH–Br bond homolytically. Since the catalyst
possesses a stable radical, interaction of which with p-Ts-NHBr
probably generates p-TsNHÅ radical, which in turn adds onto sty-
rene regiospecifically at the homobenzylic position to form ben-
zylic radical. The recombination of this radical with BrÅ radical
leads to anti-Markovnikov product. The radical pathway proposed
here has been supported by the trapping experiment with TEM-
PO,16 which failed to produce the corresponding haloamine. In
the case of other titanium salts, the formation of Markovnikov
product 2 can be reasoned on the basis of the formation of bromo-
nium ion followed by its preferential opening at the benzylic posi-
tion with p-toluenesulfonamide.
10
11
12
13
14
>99: 1
NHTs
Br
1-Octene
CH3-(CH2)5-CH-CH2NHTs
Br
Cyclohexene
Cyclooctene
Vinylcyclohexane
>99: 1
>99: 1
NHTs
Br
NHTs
Br
NHTs
Reaction conditions: aolefin (3 mmol), p-TsNH2 (3.3 mmol), N-bromosuccinimide
(3 mmol), titanium superoxide (10 wt %), CH2Cl2 (20 mL), 25 °C, 14 h.
In conclusion, we have described a titanium superoxide-cata-
lyzed regiospecific aminobromination of styrenic and other conju-
gated olefins to give exclusively anti-Markovnikov products in high
yields using p-TsNH2 and NBS as amine and bromine sources,
Products were characterized by mp, IR, 1H and 13C NMR, and elemental analysis.
b
c
Isolated yield after chromatographic purification.
Yield in parentheses refers to use of recovered catalyst.
d

T. M. Shaikh et al. / Tetrahedron Letters 50 (2009) 2815–2817
2817
Table 3
References and notes
Titanium superoxide-catalyzed regiospecific aminobromination of
a,b-unsaturated
carbonyl compoundsa
1. (a) Kemp, J. E. G.. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon: Oxford, 1991; Vol. 3, p 471; (b) Theilacker, W.; Wessel, H.
Liebigs Ann. Chem. 1967, 703, 34; (c) Ueno, Y.; Takemura, Y.; Ando, Y.; Terauchi,
H. Chem. Pharm. Bull. 1967, 15, 1193; (d) Daniher, F. A.; Melchior, M. T.; Butler,
P. E. Chem. Commun. 1968, 931; (e) Gao, G.-Y.; Harden, J. D.; Zhang, X. P. Org.
Lett. 2005, 7, 3191; (f) Yeung, Y.-Y.; Hong, S.; Corey, E. J. J. Am. Chem. Soc. 2006,
128, 6310.
2. (a) Manzoni, M. R.; Zabawa, T. P.; Kasi, D.; Chemler, S. R. Organometallics 2004,
23, 5618; (b) Michael, F. E.; Sibbald, P. A.; Cochran, B. M. Org. Lett. 2008, 10, 793.
3. Thakur, V. V.; Talluri, S. K.; Sudalai, A. Org. Lett. 2003, 5, 861.
4. (a) Li, G.; Wei, H.-X.; Kim, S. H.; Neighbors, M. Org. Lett. 1999, 1, 395; (b) Li, G.;
Wei, H.-X.; Kim, S. H. Org. Lett. 2000, 2, 2249; (c) Albone, D. P.; Aujla, P. S.;
Taylor, P. C.; Challenger, S.; Derrick, A. M. J. Org. Chem. 1998, 63, 9569; (d) Ando,
T.; Minakata, S.; Ryu, I.; Komatsu, M. Tetrahedron Lett. 1998, 39, 309; (e) Li, G.;
Wei, H.-X.; Kim, S. H. Tetrahedron 2001, 57, 8407; (f) Zhi, S.; Han, J.; Lin, C.; An,
G.; Pan, Y.; Li, G. Synthesis 2008, 10, 1570; (g) Chen, Z.-G.; Wei, J.-F.; Li, R. T.; Shi,
X.-Y.; Zhao, P.-F. J. Org. Chem. 2009, 74, 1371.
Br
O
O
R1
NHTs
4a-c
R1
R
R
3a-c
No
R
R1
Amine source
Yieldb,c (%) 4a–c
a
b
c
H
Cl
Cl
OMe
Ph
Ph
p-TsNH2
p-TsNH2
p-TsNBr2
20
21
68
Reaction conditions: aunsaturated ester (3 mmol), p-TsNH2 (3.3 mmol), N-bromo-
succinimide (3 mmol), titanium superoxide (10 wt %), CH2Cl2 (20 mL), 25 °C, 18 h.
5. Yadav, J. S.; Subba Reddy, B. V.; Chary, D. N.; Chandrakanth, D. Tetrahedron Lett.
2009, 50, 1136.
6. (a) Li, Q.; Shi, M.; Timmons, C.; Li, G. Org. Lett. 2006, 8, 625; (b) Zhang, Y.; Fu, H.;
Jiang, Y.; Zhao, Y. Synlett 2008, 2667.
Products were characterized by mp, IR, 1H and 13C NMR, and elemental analysis.
b
c
Isolated yield after chromatographic purification.
7. Zwierzak, A.; Osowska, K. Angew. Chem., Int. Ed. Engl. 1976, 15, 302.
8. Yeung, Y.-Y.; Gao, X.; Corey, E. J. J. Am. Chem. Soc. 2006, 128, 9644.
9. Wei, H.-X.; Kim, S. H.; Li, G. Tetrahedron 2001, 57, 3869.
10. (a) Wang, G.-W.; Wu, X.-L. Adv. Synth. Catal. 2007, 349, 1977; (b) Wu, X.-L.; Xia,
J.-J.; Wang, G.-W. Org. Biomol. Chem. 2008, 6, 548; (c) Xia, J.-J.; Wu, X.-L.; Wang,
G.-W. ARKIVOC 2008, xvi, 22; (d) Fan, R.; Wen, F.; Qin, L.; Pu, D.; Wang, B.
Tetrahedron Lett. 2007, 48, 7444.
11. (a) Kharasch, M. S.; Priestley, H. M. J. Am. Chem. Soc. 1939, 61, 3425; (b)
Chabrier, F. Ann. Chem. 1942, 17, 353; (c) Foglia, T. A.; Swern, D. J. Org. Chem.
1966, 31, 3625; (d) Schrage, K. Tetrahedron Lett. 1966, 7, 5795; (e) Sliwinska, A.;
Zwierzak, A. Tetrahedron Lett. 2003, 44, 9323; (f) Sliwinska, A.; Zwierzak, A.
Tetrahedron 2003, 59, 5927; (g) Klepacz, A.; Zwierzak, A. Tetrahedron Lett. 2001,
42, 4539; (h) Lessard, J.; Driguez, H.; Vermes, J.-P. Tetrahedron Lett. 1970, 11,
4887; (i) Ponsold, K.; Ihn, W. Tetrahedron Lett. 1970, 11, 1125.
p-TsNH2
NBS
p-TsNH-Br
Ti_O_O
12. (a) Wu, X.-L.; Wang, G.-W. J. Org. Chem. 2007, 72, 9398; (b) Han, J.-H.; Zhi, S.-J.;
Wang, L.-Y.; Pan, Y.; Li, G. Eur. J. Org. Chem. 2007, 1332.
13. Xu, X.; Kotti, S. R. S.; Liu, J.; Cannon, J. F.; Headley, A. D.; Li, G. Org. Lett. 2004, 6,
4881.
14. (a) Preparation of titanium superoxide:Aq 50% H2O2 (5.98 g, 0.175 mol) was
added slowly to a solution of titanium isopropoxide (5.0 g, 0.0175 mol) in
anhydrous MeOH (50 ml) over 40 min under N2 with stirring at room
temperature. The yellow precipitate formed was collected by filtration on a
sintered funnel, washed with anhydrous methanol, and dried at room
temperature. Yield: 3.94 g (98%).(b) Typical experimental procedure for
Br
p-TsNH---Br---OOTi
NHTs
Br
Ph
Ph
Ti_O_O_Br
NHTs
Ph
aminobromination of styrene:To
a stirred solution of styrene (0.312 g,
Figure 1. Titanium superoxide catalytic cycle for bromoamination process.
3.0 mmol), titanium superoxide (0.030 g, 10 wt %) and p-TsNH2 (0.564 g,
3.3 mmol) in 25 mL of dry dichloromethane was added NBS (0.534 g,
3.0 mmol) slowly using a solid addition funnel. The reaction mixture was
stirred further at 25 °C for 14 h. When TLC showed the completion of the
reaction, the catalyst was filtered off and the filtrate was diluted with water,
extracted with CH2Cl2 (20 Â 3 mL), and washed with brine. The organic layer
was dried over anhydrous sodium sulfate and concentrated under reduced
pressure to give the crude product, which was purified by column
chromatography packed with silica gel using pet ether and EtOAc as eluents
to afford the pure bromoaminated product.
respectively under ambient conditions. The protocol makes use of
stable and readily accessible titanium superoxide as solid catalyst
for the aminobromination process.
Acknowledgments
15. (a) Dewkar, G. K.; Nikalje, M. D.; Sayyed, I. A.; Paraskar, A. S.; Jagtap, H. S.;
Sudalai, A. Angew. Chem., Int. Ed. 2001, 40, 405; (b) Dewkar, G. K.; Shaikh, T. M.;
Pardhy, S.; Kulkarni, S. S.; Sudalai, A. Indian J. Chem. B 2005, 44, 1530.
16. (a) Connolly, T. J.; Baldovi, M. V.; Mohtat, N.; Scaiano, J. C. Tetrahedron Lett.
1996, 37, 4919; (b) Kim, T.-H.; Dokolas, P.; Feeder, N.; Giles, M.; Holmes, A. B.;
Walthar, M. Chem. Commun. 2000, 2419; (c) Beckwith, A. L. J.; Bowry, V. W.;
Moad, G. J. Org. Chem. 1988, 53, 1632.
T.M.S. and P.K. thank the Department of Science and Technol-
ogy, New Delhi for financial support (No. SR/S1/OC-72/2006). The
authors are also thankful to Dr. B.D. Kulkarni, Dy. Director, for his
constant encouragement.