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7019
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4203–4204; (b) Fowler, F. W.; Hassner, A.; Levy, L. A. J.
Am. Chem. Soc. 1967, 89, 2077–2082.
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Tetrahedron Lett. 2002, 43, 1201.
11. (a) Hassner, A.; Boerwinkle, F. J. Am. Chem. Soc. 1968,
90, 216–218; (b) Boerwinkle, F.; Hassner, A. Tetrahedron
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acts very slowly with NBS and TMSN3 and after 12 h, a
1:1 mixture of bromoazide 2a and dibromide 3a was ob-
tained in poor yield (Table 1, entry 1). When substrate
1a was treated with 0.05 equiv of Zn(OTf)2, 1.2 equiv
of NBS and 1.5 equiv of TMSN3 in CH2Cl2 at 0 ꢁC
for 10 min, bromoazide 2a was obtained regioselectively
in 85% yield (entry 7).
Various alkenes were subjected to the catalytic bromo-
azidation reaction (Table 2).14,15 In all the cases, the
reactions were anti-selective as revealed by the 1H
NMR of the crude products.
a,b-Unsaturated carbonyl compounds represent a syn-
thetically useful class of substrates for various alkene
oxidative reactions. In particular, bromoazidation of
a,b-unsaturated carbonyl compounds would provide
functionalized azidobrominated compounds, which
could be transformed into various useful organic com-
pounds by replacing the bromine atom with a series of
nucleophiles and where the azido functionality would
serve as a protected amino group. However, haloazida-
tion of a,b-unsaturated carbonyl compounds has been
poorly investigated. When chalcones and cinnamates
were subjected to the Zn(OTf)2 catalyzed bromoazida-
tion reaction with NBS and TMSN3 at 45 ꢁC, anti-a-
bromo-b-azido carbonyl compounds were obtained with
moderate to good yields (Table 3).16,17 At 0 ꢁC or rt, the
bromoazidation reaction of a,b-unsaturated carbonyl
compounds was found to be very slow.
12. Olah, G. O.; Wang, Q.; Li, X.-Y.; Prakash, G. K. S.
Synlett 1990, 487–489.
13. (a) Hajra, S.; Bhowmick, M.; Karmakar, A. Tetrahedron
Lett. 2005, 46, 3073–3077; (b) Hajra, S.; Maji, B.;
Karmakar, A. Tetrahedron Lett. 2005, 46, 8599–8603.
14. General procedure: To
a well stirred suspension of
˚
substrate 1 (0.50 mmol) and 4 A MS (0.100 g) in dry
CH2Cl2 (2.5 mL) was added Zn(OTf)2 (0.009 g,
0.025 mmol) under argon. The reaction mixture was
cooled to 0 ꢁC. TMSN3 (0.1 mL, 0.75 mmol) and NBS
(0.107 g, 0.60 mmol) were successively added. On comple-
tion (TLC), the reaction was quenched with aqueous
saturated NaHCO3 solution and extracted with CH2Cl2
(3 · 30 mL). The combined organic layer was washed
with water, dried over Na2SO4 and concentrated under
vacuum. The bromoazide product was purified by flash
column chromatography using petroleum ether–EtOAc
as an eluent.
15. All the compounds listed in Table 2 were characterized
by 1H NMR, 13C NMR and FT-IR spectroscopy. Spectral
data of compound ( )-2d were compared with the
literature data.7
In conclusion, we have developed a new metal triflate
catalyzed 1,2-bromoazidation of alkenes using NBS
and TMSN3 as the bromine and azide sources, respec-
tively. Zn(OTf)2 was found be the best catalyst. This
catalytic method provides stereoselectively anti-1,2-
azidobrominated products from a variety of alkenes
including a,b-unsaturated carbonyl compounds.
Representative spectral data of bromoazide ( )-2c:
Oily liquid; IR (CHCl3, cmÀ1): 2101 (N3); 1H NMR
(200 MHz, CDCl3):
d 2.11–2.30 (m, 1H), 2.35–2.55
(m, 1H), 2.80–3.20 (m, 2H), 4.42–4.51 (m, 1H), 4.74
(d, J = 4.5 Hz, 1H), 7.10–7.38 (m, 4H); 13C NMR
(50 MHz, CDCl3): d 25.9, 27.8, 50.3, 65.1, 126.6, 128.7,
129.1, 129.7, 130.5, 135.3.
Acknowledgements
16. General procedure for chalcones and cinnamates: To a
well stirred suspension of chalcone or cinnamate 1
We thank DST (Project No. SR/S1/OC-13/2004), New
Delhi, for providing financial support. D.S. and M.B.
thank CSIR, New Delhi, and IIT, Kharagpur, respec-
tively, for their fellowships.
˚
(0.50 mmol) and 4 A MS (0.100 g) in dry CH2Cl2
(2.5 mL) were successively added Zn(OTf)2 (0.009 g,
0.025 mmol), TMSN3 (0.1 mL, 0.75 mmol) and NBS
(0.107 g, 0.60 mmol) under argon. The reaction mixture
was heated (45 ꢁC) under reflux. The reaction was mon-
itored by TLC and upon completion was quenched with
saturated aqueous NaHCO3 solution and extracted with
CH2Cl2 (3 · 30 mL). The combined organic layer was
washed with water, dried over Na2SO4 and concentrated
under vacuum. The bromoazide product was purified
by flash column chromatography using petroleum ether–
EtOAc as an eluent.
References and notes
1. Hassner, A.; Fowler, F. W. J. Org. Chem. 1968, 33, 2686–
2691.
2. Wasserman, H. H.; Brunner, R. K.; Buynak, J. D.; Carter,
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107, 519–521.
3. For the synthesis of tetrazoles via Hassner–Ritter reaction:
(a) Ranganathan, S.; Ranganathan, D.; Mehrotra, A. K.
Tetrahedron Lett. 1973, 14, 2265–2268; (b) Moorthy, S. N.;
Devaprabakara, D. Tetrahedron Lett. 1975, 16, 257–
260.
4. (a) Van Ende, D.; Krief, A. Angew. Chem., Int. Ed. Engl.
1974, 13, 279–280; (b) Denis, J. N.; Krief, A. Tetrahedron
1979, 35, 2901–2903.
17. All the compounds listed in Table 3 were characterized by
1H NMR, 13C NMR and FT-IR spectroscopy.
Representative spectral data of a-bromo-b-azido carbonyl
compound ( )-2j: Gummy liquid; IR (CHCl3, cmÀ1): 2108
1
(N3), 1745 (CO); H NMR (200 MHz, CDCl3): d 3.83 (s,
3H), 3.87 (s, 3H), 4.27 (d, J = 10.7 Hz, 1H), 4.91 (d,
J = 10.7 Hz, 1H), 6.94 (d, J = 8.5 Hz, 2H), 7.27 (d,
J = 8.6 Hz, 2H); 13C NMR (50 MHz, CDCl3):
d
46.0, 53.2, 55.1, 66.7, 114.1 (2C), 126.9, 129.1 (2C), 160.2,
168.5.
5. Hantzsch, A.; Schumann, M. Ber. Dtsch. Chem. Ges. 1900,
¨
33, 522.