B. Jiang et al. / Tetrahedron Letters 42 (2001) 4083–4085
4085
NO2
Cl
NH2
O
1, NaIO4/OsO4
2. H2/R-Ni
F3C
CF3
CF3
Cl
ref. 9
O
89%
N
H
O
Cl
4e
5
6 Efavirenz
Scheme 3.
methyl)ethenyl boronic acid 2 could be extended to aryl
bromides bearing strong electron withdrawing groups
in the aryl ring (entries 4–5). In addition, 2-naphthyl
bromide 3f and 2-amino-3-methoxy-5-bromopyrazine
3g (entries 6–7) also underwent the palladium-catalysed
coupling reaction with a-(trifluoromethyl)ethenyl
boronic acid 2 to give the coupling products in excellent
yields.
2. (a) New Fluorinating Agents in Organic Synthesis; Ger-
man, L; Zemskov, S., Eds.; Springer-Verlag: Berlin,
Heidelberg, 1989; (b) Synthetic Fluorine Chemistry; Olan,
G. A.; Surya Prakash; Chambers, R. D., Eds.; John
Wiley & Son: New York, 1992.
3. (a) Petasis, N. A.; Goodman, A.; Zavialov, I. A. Tetra-
hedron 1997, 53, 16463; (b) Petasis, N. A.; Zavialov, I. A.
J. Am. Chem. Soc. 1997, 119, 445.
4. The Borance, Carborance, and Carbocation Continum;
Casanova, J., Ed.; John Wiley & Son: New York, 1998.
5. (a) Jiang, B.; Xu, Y. Y. J. Org. Chem. 1991, 56, 7336; (b)
Jiang, B.; Xu, Y. Y. Tetrahedron Lett. 1992, 33, 511.
6. Henne, A. L.; Nager, M. J. Am. Chem. Soc. 1951, 73,
1042.
It is known that the trifluoroketone 5 is an important
intermediate for the preparation of efavirenz,9 which is
a
potent nonucleosidal HIV reverse transcriptase
inhibitor approved by the FDA for the treatment of
AIDS.10 The trifluoroketone 5 has been synthesised
from the reaction between n-butyllithium and an N-
protected aniline with ethyl trifluoroacetate at low tem-
perature. This process suffers from high cost and strict
reaction conditions.11 The a-trifluoromethylstyene 4e
was easily converted into ketone 5 in high yield simply
by oxidation of the ethenyl bond using NaIO4 and
catalytic OsO4 (0.01 equiv.) in tert-BuOH/H2O (4:1),
followed by hydrogenation over Raney Ni in ethanol
(Scheme 3).
7. The procedure for preparation of boronic acid 2: A
mixture of BrTFP (1.75 g, 10 mmol), magnesium (0.29 g,
12 mmol) and trimethyl borate (3.12 g, 30 mmol) in
anhydrous THF (20 mL) stirred at rt for 4 h. Then, 6 M
HCl (50 mL) was added to the reaction mixture. The
organic layer was separated and the aqueous layer was
extracted with diethyl ether (3×20 mL). The combined
extract was washed with brine and evaporated to give 2
(126 mg, 90%), which was enough pure to be used for
Suzuki cross coupling reaction. 19F NMR lTFA: −12.0 (s,
In summary, the a-(trifluoromethyl)ethenyl boronic
acid 2 was conveniently prepared from 2-bromotri-
fluoropropene, an alkyl borate and magnesium in a
one-pot process. The palladium-catalysed cross cou-
pling of this boronic acid with aryl halides provides an
efficient method for the preparation of a-tri-
fluoromethylstyrene derivatives under mild conditions.
The stability and tolerance to air and moisture of this
reagent allow easy storage and manipulation. The syn-
thetic utility of the a-(trifluoromethyl)ethenyl boronic
acid in Suzuki cross coupling reactions has revealed the
potential of this reagent as a new versatile tri-
fluoromethyl containing building block for the synthesis
of bioactive trifluoromethylated organic compounds.
1
3F) ppm; H NMR(CDCl3) l: 6.72 (s, 2H) ppm; MS(EI)
m/z: 140 (M+), 121 (M+−F), 70 (M+−1−CF3).
8. (a) Watanebe, T.; Miyaura, N.; Suzuki, A. Synlett 1992,
207; (b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95,
2457.
9. (a) Thompson, A.; Corley, E. C.; Huntington, M. F.;
Crabowski, E. J. J.; Remenar, J. F.; Collum, D. B. J. Am.
Chem. Soc. 1998, 120, 2028; (b) Tan, L.; Chen, C. Y.;
Tillyer, R. D.; Grabowski, E. J. J.; Reider, P. J. Angew.
Chem., Int. Ed. Engl. 1999, 38, 711.
10. Young, S. D.; Britcher, S. F.; Tan, L.; Payne, L. S.;
Lumma, W. C.; Lyle, T. A.; Huff, J. R.; Anderson, P. S.;
Olsen, D. B.; Carroll, S. S.; Pettibone, D. J.; O’Brien, J.
A.; Ball, R. G.; Balani, S. K.; Lin, J. H.; Chen, I. W.;
Schleif, W. A.; Sardana, V. V.; Long, W. J.; Byrnes, V.
W.; Emini, E. A. Antimicrob. Agents Chemother. 1995,
39, 2602.
References
11. (a) Huffman, M. A.; Yasuda, N.; DeCamp, A. E.;
Grabowski, E. J. J. J. Org. Chem. 1995, 60, 1590; (b)
Thompson, A. S.; Corely, E. G.; Huntington, M. F.;
Grabowski, E. J. J. Tetrahedron Lett. 1995, 36, 8937.
1. Filler, R.; Kobayashi, Y.; Yagupoyashi, L. M.
Organofluororine Compounds in Medicinal Chemistry and
Biomedical Application; Elservier Science: Amsterdam,
1993.
.