ORGANIC
LETTERS
2003
Vol. 5, No. 8
1167-1169
Fluorous Solvent as a New
Phase-Screen Medium between
Reagents and Reactants in the
Bromination and Chlorination of
Alcohols
,†
Hiroyuki Nakamura,* Taikou Usui,† Hirokazu Kuroda,† Ilhyong Ryu,‡
Hiroshi Matsubara,‡ Shinji Yasuda,‡ and Dennis P. Curran§
Department of Chemistry, Faculty of Science, Gakushuin UniVersity,
Mejiro, Tokyo 171-8588, Japan, Department of Chemistry, Faculty of Arts and
Sciences, Osaka Prefecture UniVersity, Sakai, Osaka 599-8531, Japan, and
Department of Chemistry, UniVersity of Pittsburgh, Pittsburgh, PennsylVania 15260
Received January 13, 2003
ABSTRACT
A perfluorohexane layer regulates the rate of reagent transport in the bromination and chlorination of alcohols. A fluorous triphasic U-tube
method is effective for lighter reagents; the thionyl chloride layer (yellow) vanishes, and the chlorides are obtained from the right top organic
layer in the chlorination of alcohols.
Since fluorous biphasic reactions were introduced to organic
synthesis,1 much attention has been paid to the strategic new
option of a fluorous technique for conducting organic
reactions and for separating the reaction mixtures.2 Fluorous
biphasic reactions are based upon an interaction among
fluorous solvents and fluorous compounds such as catalysts,
reagents, and reactants; unfluorinated products are usually
extracted from a fluorous phase into an organic phase, and
fluorinated compounds are recovered from a fluorous phase
at the end of reactions.3,4 As another use for the fluorous
technique, we recently found that a fluorous solvent acts as
a phase-screen medium in the bromination of alkenes and
in the demethylation of aromatic methyl ethers for regulation
of the rate of reagent addition.5 This is important for
controlling heat evolution in exothermic reactions, especially
(3) (a) Cavazzini, M.; Montanari, F.; Pozzi, G.; Quici, S. J. Fluorine
Chem. 1999, 94, 183. (b) Fish, R. H. Chem. Eur. J. 1999, 5, 1677. (c) de
Wolf, E.; van Koten, G.; Deelman, B. J. Chem. Soc. ReV. 1999, 28, 37. (d)
Dinh, L. V.; Gladysz, J. Tetrahedron Lett. 1999, 40, 8995. (e) Nakamura,
Y.; Takeuchi, S.; Ohgo, Y.; Curran, D. P. Tetrahedron Lett. 2000, 41, 57.
(f) Alvey, L. J.; Meier, R.; Soos, T.; Bernatis, P.; Gladysz, J. A. Eur. J.
Org. Chem. 2000, 1975. (g) Rocaboy, C.; Bauer, W.; Gladysz, J. A. Eur.
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D.; Chadwick, D.; Henschke, J. P.; McKinnell, R. M. Synlett 2000, 847.
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P.; Hoshino, M. J. Org. Chem. 1996, 61, 6480. (c) Studer, A.; Hadida, S.;
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Y.; Luo, Z. J. Am. Chem. Soc. 1999, 121, 6607. (f) Linclau, B.; Sing, A.
K.; Curran, D. P. J. Org. Chem. 1999, 64, 2835. (g) Curran, D. P.; Luo, Z.
J. Am. Chem. Soc. 1999, 121, 9069. (h) Luo, Z.; Zhang, Q.; Oderaotoshi,
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† Gakushuin University.
‡ Osaka Prefecture University.
§ University of Pittsburgh.
(1) (a) Horva´th, I. T.; Ra´bai, J. Science 1994, 266, 72. (b) Horva´th, I. T.
Acc. Chem. Res. 1998, 31, 641.
(2) (a) Curran, D. P. Angew. Chem., Int. Ed. 1998, 37, 1175. (b) Cornils,
B. Angew. Chem., Int. Ed. Engl. 1997, 36, 2057. (c) Kitazume, T. J. Fluorine
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(5) (a) Ryu, I.; Matsubara, H.; Yasuda, S.; Nakamura, H.; Curran, D. P.
J. Am. Chem. Soc. 2002, 124, 12946. (b) Matsubara, H.; Yasuda, S.; Ryu,
I. Synlett 2003, 247.
10.1021/ol034060w CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/19/2003