4028
T. A. Salama, Z. Novák / Tetrahedron Letters 52 (2011) 4026–4029
O
O
OH
Ar
Ar
X
X
R
1
Ar
2,3,5
R
R
SiCl4
MeCN, r.t.
H2O
Cl4Si
O
OSiCl3
Ar
OSiCl3
Ar
OSiCl3
OSiCl3
X
R
SiCl4
X
X
NXS
N X
Ar
Ar
R
R
R
A
B
O
Scheme 3.
1151–1152; (f) Garbisch, E. W., Jr. J. Org. Chem. 1965, 30, 2109–2120; (g) Julian,
P. L.; Karpel, W. J. J. Am. Chem. Soc. 1950, 72, 362–366.
good yield of the corresponding benzyl chloride 9 after aqueous
work-up (Table 2, entry 8).
6. For a review, see: (a) Larock, R. C. Comprehensive Organic Transformations,
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The structures of the isolated benzyl bromide derivatives were
assigned based on spectral analyses as well as by comparison of
their physical properties with reported analogues. Although the
exact radical chain process is not quite clear, the reaction would
appear to proceed via a radical mechanism under ambient condi-
tions in the presence of light, in a manner similar to the reported
Lewis acid catalyzed benzylic bromination.18 On the other hand,
a reasonable pathway for the
a-halogenation of carbonyl com-
pounds may agree with that depicted in Scheme 3 involving reac-
tion of enolisable ketone 1 with SiCl4 to give chlorosilyl enolate A.
The excess TCS may coordinate with the carbonyl oxygen of the
N-halosuccinimide increasing the activity of the halogen atom.
Next, attack of A on the halogen of NXS would produce the haloge-
nated silyl enolate B which gives the desired product after aqueous
work-up. This postulation is in agreement with the well-docu-
mented reaction of silyl enol ethers with N-halosuccinimides.22
A
radical intermediate involving addition of the halogen to an enol
silyl ether can also be similarly invoked.22,23
In conclusion, we have developed a practical and efficient meth-
od for the a-monohalogenation of carbonyl compounds as well as
for benzylic halogenation by using cheap and readily available tetra-
chlorosilane and N-halosuccinimides.24 This method can be applied
to a wide range of carbonyl compounds and alkyl benzene deriva-
tives; the halogen atom can be introduced to the substrate with high
regioselectivity. The mild reaction conditions, easy work-up proce-
dure and simple operation are advantages of this procedure.
12. Moorthy, J. N.; Senapati, K.; Singhal, N. Tetrahedron Lett. 2009, 50, 2493–2496.
13. Yadav, J. S.; Reddy, B. V. S.; Singh, A. P.; Basak, A. K. Tetrahedron Lett. 2008, 49,
5880–5882.
14. Patil, R. D.; Joshi, G.; Adimurthy, S.; Ranu, B. C. Tetrahedron Lett. 2009, 50, 2529–
2532.
15. (a) Srimani, D.; Bej, A.; Sarkar, A. J. Org. Chem. 2010, 75, 4296–4299; (b) Zhang,
W.-W.; Zhang, X.-G.; Li, J.-H. J. Org. Chem. 2010, 75, 5259–5264; (c) Zhou, W.;
Xu, J.; Zhang, L.; Jiao, N. Org. Lett. 2010, 12, 2888–2891; (d) Xiao, Q.; Ma, J.;
Yang, Y.; Zhang, Y.; Wang, J. Org. Lett. 2009, 11, 4732–4735; (e) Davies, K. A.;
Abel, R. C.; Wulff, J. E. J. Org. Chem. 2009, 74, 3997–4000; (f) Surpateanu, G.;
Dron, P. I.; Landy, D.; Fourmentin, S.; Bria, M. Tetrahedron 2008, 64, 721–732.
16. Selected recent examples of benzylic halogenation with N-haloimides: (a)
Jereb, M.; Zupan, M.; Stavber, S. Helv. Chim. Acta 2009, 92, 555–566; (b)
Heropoulos, G. A.; Cravotto, G.; Screttas, C. G.; Steele, B. R. Tetrahedron Lett.
2007, 48, 3247–3250; (c) Zhang, Y.; Shibatomi, K.; Yamamoto, H. Synlett 2005,
2837–2842; (d) Podgorsek, A.; Stavber, S.; Zupan, M.; Iskra, J. Tetrahedron Lett.
2006, 47, 1097–1099.
Acknowledgments
We would like to thank Dr. Anna Komáromi and Gergely Tolnai
for NMR and MS measurements. T.A.S. is grateful to the Hungarian
Scholarship Board (HSB) for a post-doctoral fellowship.
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