666
B. Jiang et al. / Tetrahedron Letters 43 (2002) 665–667
Table 1. Reaction of 1 with active methylene compounds 3 and NaH followed by intramolecular cyclization and dehydro-
sulfination
Entry
R
EWG
Temp. (°C)/Time (h)
Yield (%) of 4a (stereochemistry)
Yield (%) of 6
Ab
Bc
1
2
3
4
5
6
7
8
CH3
C2H5
n-C3H7
Ph
CO2Et 3a
CO2Et 3b
CO2Et 3c
CO2Et 3d
CN 3e
CN 3f
CN 3g
CN 3h
CN 3i
60/6
60/9
60/9
60/4
80/10
80/16
80/24
80/26
80/26
80/30
91 (1E,3E) 4a
90 (1E,3E) 4b
89 (1E,3E) 4c
87 (1E,3E) 4d
85 (1E,3E) 4e
81 (1E,3E) 4f
90 (1E,3E) 4g
93 (1E,3E) 4h
80 (1E,3E) 4i
15 (1E,3E) 4j
81
86
87
91
90
93
92
90
92
91
0
0
0
0
6a
6b
6c
6d
Ph
85 6e
93 6f
85 6g
91 6h
90 6i
85 6j
p-CH3C6H4
p-CH3OC6H4
m-CH3C6H4
p-MeO2CC6H4
o-Ph-C6H4
9
10
CN 3j
a The reaction was carried out with 1 equiv. 1, 1.2 equiv. NaH and 1 equiv. 3 in THF.
b Refluxing in decalin.
c Refluxing in acetic acid/sodium acetate/1,4-benzoquinone.
O
CF3
alkoxides to form trifluoromethylvinyl ethers. Based on
this fact, we sought a method for carbonꢀcarbon bond
formation via nucleophilic addition of carbanions to
the acetylene 2. We found that compound 2 (19F NMR
lTFA: −27.5, s), generated in situ from 2-bromo-2-tri
fluoromethylethenyl phenyl sulfide 1 by treatment with
1.2 equiv. of NaH in THF, smoothly reacted with
active methylene compounds 3 to give the Michael
addition products 4.9 The carbanion attacked the acetyl-
ene 2 in the b-position regioselectively to afford diene 4
with (1E,3E)-geometry stereoselectively. Due to the
presence of the strong electron-withdrawing group
(EWG) in the molecule, the enol form was produced
exclusively. The stereochemistry was defined on the
R=CH3, C2H5, n-C3H7, Ph
R
SPh
7
In summary, the addition of carbon nucleophiles to
trifluoromethyl phenylsulfanyl acetylene provides an
efficient method for the regio- and stereoselective syn-
thesis of a wide range of functionalized (1E,3E)-tri-
fluoromethylated 1,3-diene derivatives in high yields. The
synthetic utility of trifluoromethylated 1,3-dienes lies in
a novel and easy approach to 3-trifluoromethylated
furans. This method has the advantage of ready accessi-
bility of the reagent, mild conditions as well as its
simplicity in manipulation.
1
basis of H NMR, 19F NMR (lTFA: −13.8, s) and IR
spectra. The IR spectrum contained a broad band
(3300–3100 cm−1) assigned to an O–H stretch. Further
confirmation of the structure was afforded by an X-ray
structure analysis of compound 4e. As shown in Table
1, the reaction of compound 1 with alkyl keto-acetates
(entries 1–3) or benzoylacetate (entry 4) with NaH in
THF gave dienes 4a–4d within 6–8 h at 60°C, while the
reactions of aryl keto-acetonitriles (entries 5–10) pro-
ceeded sluggishly at 80°C, but could be readily com-
pleted in 10–30 h to afford dienes 4e–4j in high yields.
Acknowledgements
The research was supported by the Shanghai Overseas
Scholarship and the National Natural Scientific Foun-
dation of China.
References
Taking advantage of the ease of preparation of
(1E,3E)-2-trifluoromethyl-4-hydroxy-dienes, we have
demonstrated the possibility of making CF3-substituted
furans by intramolecular cyclization. Initially, we tried
to prepare furan 6 via cyclization of 4 in acetonitrile
promoted by the Lewis acid, TiCl4.10 The reaction was
however unsuccessful. We found that if compounds 4
were heated in decalin at 190°C for 3 h, the expected
intramolecular cyclization products, 3-trifluoromethyl-
ated furans 6, could be isolated in high yields with
concurrent elimination of thiophenol (Table 1).11 Using
acetic acid as a proton source, compounds 4e–4j were
heated with sodium acetate and 1,4-benzoquinone at
100°C for 24 h to yield the furans 6e–6j in excellent
yields, while compounds 4a–4d gave the decarboxylated
product 7, quantitatively.
1. Welch, J. T.; Eswarakrishnan, S. Fluorine in Bioorganic
Chemistry; John Wiley & Sons: New York, 1991.
2. Kameswaran, V.; Jiang, B. Synthesis 1997, 530.
3. Shi, G.; Xu, Y. J. Chem. Soc., Chem. Commun. 1989, 607.
4. Burger, K.; Helmreich, B. J. Chem. Soc., Chem. Commun.
1992, 348.
5. (a) Barlow, M. G.; Suliman, N. N. E.; Tipping, A. E. J.
Fluorine Chem. 1995, 70, 59; (b) Chambers, R. D.; Roch,
M. H. J. Chem. Soc., Perkin Trans. 1 1996, 1095.
6. Nowak, I.; Dmowski, W.; Marks, W. A. J. Fluorine
Chem. 1995, 75, 115.
7. Hu, C. M.; Hong, F.; Jiang, B.; Xu, Y. Y. J. Fluorine
Chem. 1994, 66, 215.
8. Jiang, B. J. Chem. Soc., Chem. Commun. 1996, 861.