Papori Goswami et al.
COMMUNICATIONS
ficient asymmetric a-bromination of b-keto esters, Acknowledgements
cyclic ketones and 1,3-diketones with good enantiose-
The work was carried out with the financial grant No. SR/
FTP/CS-15/2007 of DST, New Delhi, India. The Director,
IITG is given special thanks for providing the required re-
search facility to carry out the work. The reviewers are
thanked for their valuable suggestions.
lectivity. The organic brominating reagent can be re-
covered and reused after each cycle. The technique of
isolation of the pure products from the reaction mix-
ture without column chromatography is a major asset
of this protocol. We hope that the idea will contribute
to the field of enantioselective bromination.
References
Experimental Section
[1] For recent reviews on asymmetric halogenation reac-
tions, see: a) M. Oestreich, Angew. Chem. 2005, 117,
2376; Angew. Chem. Int. Ed. 2005, 44, 2324; b) S.
France, A. Weatherwax, T. Lectka, Eur. J .Org. Chem.
2005, 475; c) H. Ibrahim, A. Togni, Chem. Commun.
2004, 1147.
[2] a) M. B. Smith, J. March, in: Advanced Organic
Chemistry: Reactions, Mechanisms and Structure, 4th
edn., John Wiley & Sons, New York, 1992, pp 775–778;
b) N. De Kimpe, R. Verhe, The Chemistry of a-Halo-
ketones, a-Haloaldehydes, and a-Haloimines, Wiley,
New York, 1990.
Preparation of 2,2-Dibromo-5,5-dimethylcyclohexa-
1,3-dione
To
a clear solution of 5,5-dimethylcyclohexa-1,3-dione
(1 mol, 1.4 g) in 20 mL of ethanol:water (15:5), was added
NBS (2.1 mol, 1.95 g) (in portions) at room temperature.
The solution becomes light yellow on addition of NBS. The
reaction mixture was stirred vigorously at room temperature
until the disappearance of the yellow colour.Another por-
tion of NBS was added with the reappearance of the yellow
colour. The addition of the total amount of NBS was com-
pleted after addition in four portions. The 2,2-dibromo-5,5-
dimethylcyclohexa-1,3-dione so formed precipitated out of
the solvent as white solid after the completion of the reac-
tion within 1.5 h. Water was added to the reaction mixture
and the white solid was filtered. The solid precipitate was
washed with water several times, dried and stored in an air-
tight bottle.
[3] G. Thomas, Medicinal Chemistry: An Introduction,
Wiley, New York, 2000.
[4] a) H. Ibrahim, A. Togni, Chem. Commun. 2004, 1147;
b) K. Muniz, Angew. Chem. 2001, 113, 1701; Angew.
Chem. Int. Ed. 2001, 40, 1653;.
[5] a) L. Hintermann, A. Togni, Angew. Chem. 2000, 112,
4530; Angew. Chem. Int. Ed. 2000, 39, 4359; b) L. Hin-
termann, D. Broggini, A. Togni, Helv. Chim. Acta 2002,
85, 1597; c) R. Frantz, L. Hintermann, M. Perseghini,
D. Broggini, A. Togni, Org. Lett. 2003, 5, 1709; d) Y.
Hamashima, D. Hotta, M. Sodeoka, J. Am. Chem. Soc.
2002, 124, 11240; e) Y. Hamashima, H. Takono, D.
Hotta, M. Sodeoka, Org. Lett. 2003, 5, 3225; f) D. Y.
Kim, E. J. Park, Org. Lett. 2003, 5, 1709; g) J.-A. Ma,
D. Cahard, Tetrahedron 2004, 60, 1007; h) J.-A. Ma, D.
Cahard, J. Fluorine Chem. 2004, 125, 1357; i) N. Shiba-
ta, T. Ishimaru, T. Nogai, J. Kohno, T. Toru, Synlett
2004, 1703.
[6] a) N, Shibata, E. Suzuki, Y. Takeuchi, J. Am. Chem.
Soc. 2000, 122, 10728; b) N. Shibata, E. Suzuki, T.
Asahi, Y. Takeuchi, J. Am. Chem. Soc. 2001, 123, 7001.
[7] a) D. Y. Kim, E. J. Park, Org. Lett. 2002, 4, 545;
b) D. B. Ramachary, C. F. Barbas III, Org. Lett. 2005, 7,
1577.
Bromination of Carbonyl and 1,3-Dicarbonyl
Compounds
To a solution of b-keto esters (1 mmol) in CH2Cl2 (2 mL)
under ice cooling was added d-morvaline (10 mol%). After
stirring the reaction mixture for 5 min, brominating reagent
B (1.1 mmol, 327 mg) was added to the reaction mixture fol-
lowed by PDC (1 mol%). The reaction was allowed to stir
under ice cooling until the completion of the reaction as in-
dicated by thin layer chromatography (TLC). After the
completion of the reaction, the reaction mixture was poured
into water and extracted with CH2Cl2 (2ꢁ15mL). The or-
ganic layer was dried over anhydrous Na2SO4 and evaporat-
ed under reduced pressure. The solid product so obtained
after proper drying contains a mixture of both the a-mono-
brominated product as well as the brominated reagent in its
a-monobrominated form (C). Next, the solid product was
washed with distilled hexane for three times. The required
a-monobromo product dissolved in hexane and was separat-
ed from the a-monobrominated reagent which was left
behind in its solid form because of its high polarity. The
monobromo compound so obtained was further purified
through a short column of silica and washed with hexane.
The product thus obtained in its pure form after evaporating
the hexane, was dried and directly analysed by NMR, mass
spectroscopy, GC and elemental analyses. The optical purity
of the compound was obtained directly. The compound C so
obtained in the solid form was further brominated to furnish
B and reused.
[8] a) A. E. Taggi, H. Wack, A. M. Hafez, S. France, T.
Lectka, Org. Lett. 2002, 4, 627; b) H. Wack, A. E.
Taggi, A. M. Hafez, W. J. Dury, III, T. Lectka, J. Am.
Chem. Soc. 2001, 123, 1531.
[9] G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, P. Mel-
chiorre, L. Sambri, Angew. Chem. 2005, 117, 6375;
Angew. Chem. Int. Ed. 2005, 44, 6219.
[10] A. M. Hafez, A. E. Taggi, H. Wack, J. Esterbrook, T.
Lectka, Org. Lett. 2001, 3, 2049.
[11] a) S. Bertelsen, N. Halland, S. Bachmann, M. Marigo,
A. Braunton, K. A. Jørgensen, Chem. Commun. 2005,
4821; b) J. Franzꢂn, M. Marigo, D. Fielenbach, T. C.
Wabnitz, A. Kjærsgaard, K. A. Jørgensen, J. Am.
Chem. Soc. 2005, 127, 18296.
1486
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1483 – 1487