the synthesis of 2-fluoro-1,3-dienes from the corresponding
allenylmethylsilanes (Scheme 1). This is the first route to
superior if these reactions are carried out in THF at -78 °C
instead of in ether. The starting propargylic alcohols were
prepared according to standard procedures from the literature
(Table 1).12
Scheme 1. Allenylmethylsilanes as Precursors of Fluorodienes
Table 1. Preparation of Allenylmethylsilanes 1a-i
yield
yield
entry
R
R′
product (%) product (%)
1
2
3
4
5
6
7
8
9
PhCH2CH2 Me
2a
2b
2c
2d
2e
2f
2g
2h
2i
94
95
74
91
85
99
87
64
71
1a
1b
1c
1d
1e
1f
1g
1h
1i
81
79
49
83
69
80
75
77
54
BnOCH2
nC5H11
nC5H11
Me
Ph
Me
these valuable compounds that is not based on the use of a
fluorinated building block. Indeed, fluorinated cyclopropanes7
and fluorinated unsaturated aldehydes8 are two of the most
commonly used precursors of monofluorinated dienes, which
are obtained upon ring opening and Wittig alkenylation,
respectively. Other elegant routes toward fluorinated dienes
have also been developed such as various elimination
processes9 and palladium-mediated couplings of fluorinated
precursors.10
PhCH2CH2 SiMe3
PhCH2CH2
H
H
H
H
AcOCH2
BnOCH2
Ph
Our initial studies began with allenylsilane 1a as the dienyl
transfer reagent (Table 2). Reaction of 1a with 1 equiv of
To prepare the starting allenylmethylsilanes 1a-i, we
adapted a procedure described in the literature.4b,11 Several
substituted trimethylsilylmethylbutadienes were obtained in
good overall yields by the reaction of the propargylic
mesylates 2a-i freshly prepared from the corresponding
alcohols 3a-i, with Me3SiCH2MgCl in the presence of an
excess of CuCN and LiCl. The use of these two salts is
essential for effecting γ-attack of the Grignard reagent
leading to the exclusive formation of the desired allenyl-
methylsilanes. We found that the yields are consistently
Table 2. Electrophilic Fluorination of Silane 1a
fluorinating
reagent
time
(h)
yield
4a (%)
entry
solvent
additive
1
2
3
4
5
6
7
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
NFSI
acetonitrile
acetone
THF
MeOH
acetonitrile NaHCO3
120
120
120
21
27
27
51a
49
5
43b
60
64
39
(7) (a) Patrick, T. B.; Rogers, J.; Gorrell, K. Org. Lett. 2002, 4, 3155-
3156. (b) Bessard, Y.; Kuhlmann, L.; Schlosser, M. Tetrahedron 1990, 46,
5230-5236. (c) Schlosser, M.; Dahan, R.; Cottens, S. HelV. Chim. Acta
1984, 67, 284-288. (d) Spahi, B.; Schlosser, M. HelV. Chim. Acta 1980,
63, 1242-1256. (e) Molines, H.; Wakselman, C. Tetrahedron 1976, 32,
2099-2103. (f) Seyferth, D.; Jula, T. F.; Mueller, D. C.; Mazerolles, P.;
Manuel, G.; Thoumas, F. J. Am. Chem. Soc. 1970, 92, 657-666. (g)
Weyerstahl, P.; Klamann, D.; Finger, C.; Fligge, M.; Nerdel, F.; Buddrus,
J. Chem. Ber. 1968, 101, 3-1311. (h) Shi, G.-Q.; Schlosser, M. Tetrahedron
1993, 49, 1445-1456. (i) Shi, G.-Q.; Cottens, S.; Shiba, S. A.; Schlosser,
M. Tetrahedron 1992, 48, 10569-10574.
acetone
acetone
NaHCO3
NaHCO3
48
a 4a was contaminated with 5% of 5a. b Ratio of 4a:5a ) 2:1.
(8) (a) Ni, J.; Liu, J.; Colmenares, L. U.; Liu, R. S. H. Tetrahedron Lett.
2001, 42, 1643-1644. (b) Liu, J.; Colmenares, L. U.; Liu, R. S. H.
Tetrahedron Lett. 1997, 38, 8495-8498. (c) Francesca, A.; Alvarez, R.;
Lo´pez, S.; de Lera, A. R. J. Org. Chem. 1997, 62, 310-319. (d) Matsuo,
N.; Kende, A. S. J. Org. Chem. 1988, 53, 2304-2308.
Selectfluor in acetonitrile afforded 51% of the desired
fluorinated diene 4a after 120 h. This compound was
contaminated with 5% of the nonfluorinated diene 5a
resulting from a protodesilylation process (entry 1). The use
of acetone as the reaction solvent did not result in any
substantial changes, whereas THF was found not to be
suitable for this transformation (entries 2 and 3). Methanol
was also tested as a solvent for this transformation, allowing
the formation of the desired diene 4a along with the
undesired nonfluorinated diene 5a in 43% combined yield
(9) Patel, S. T.; Percy, J. M.; Wilkes, R. D. Tetrahedron 1995, 51,
11327-11336. (b) Hedhli, A.; Bakloutti, A. Tetrahedron Lett. 1995, 36,
4433-4436.
(10) (a) Gernert, D. L.; Ajamie, R.; Ardecky, R. A.; Bell, M. G.;
Leibowitz, M. D.; Mais, D. A.; Mapes, C. M.; Michellys, P. Y.; Rungta,
D.; Reifel-Miller, A.; Tyhonas, J. S.; Yumibe, N.; Grese, T. A. Bioorg.
Med. Chem. Lett. 2003, 13, 3191-3195. (b) Peng, S.; Qing, F.-L.; Li, Y.-
Q.; Hu, C.-M. J. Org. Chem. 2000, 65, 694-700.
(11) (a) Ajamian, A.; Gleason, J. L. Org. Lett. 2003, 5, 2409-2411. (b)
Matsuda, F.; Kawatsura, M.; Hosaka, K.-I.; Shirahama, H. Chem. Eur. J.
1999, 5, 3252-3259. (c) Osa, Y.; Kobayashi, S.; Sato, Y.; Suzuki, Y.;
Takino, K.; Takeuchi, T.; Miyata, Y.; Sakaguchi, M.; Takayanagi, H. J.
Med. Chem. 2003, 46, 1948-1956. (d) Wipf, P.; Rahman, L. T.; Rector, S.
R. J. Org. Chem. 1998, 63, 7132-7133. (e) Wrobel, J.; Li, Z.; Dietrich,
A.; McCaleb, M.; Mihan, B.; Sredy, J.; Sullivan, D. J. Med. Chem. 1998,
41, 1084-1091.
1
in a ratio of ca. 2:1 as judged by H NMR analysis of the
purified material after 21 h. As expected, this polar protic
solvent favors the protodesilylation process but also sub-
(12) Experimental details can be found in Supporting Information.
1268
Org. Lett., Vol. 7, No. 7, 2005