Chemistry Letters 2002
283
Thomas, J. Chem. Soc., Chem. Commun., 1976, 736;J. E. Baldwin,
R. C. Thomas, L. I. Kruse, and L. Silberman, J. Org. Chem., 42,
3846 (1977).
2
For recent reports, see: A. F. Parsons, C. R. Acad. Sci., Ser. IIC:
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Martin, A. R. Kennedy, D. Lizos, and J. A. Murphy, Org. Lett., 3,
3405 (2001) and references therein.
3
4
For recent reports, see: A. D. Jones, D. W. Knight, and D. E. Hibbs,
J. Chem. Soc., Perkin Trans. 1, 2001, 1182 and references therein.
a) J. J. Caldwell, D. Craig, and S. P. East, Synlett, 2001, 1602 and
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G. Petrillo, and C. Tavani, Eur. J. Org. Chem., 2000, 903 and
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Thorimbert and M. Malacria, Tetrahedron Lett., 39, 9659 (1998). i)
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J. Ichikawa, Y. Wada, T. Okauchi, and T. Minami, Chem.
Commun., 1997, 1537;J. Ichikawa, M. Fujiwara, Y. Wada, T.
Okauchi, and T. Minami, Chem. Commun., 2000, 1887.
After our findings on the unusual reactivity of gem-difluoroolefins
in 5-endo-trig cyclization,5 examples based on the same concept as
ours have been reported: a) T. Yamazaki, S. Hiraoka, J. Sakamoto,
and T. Kitazume, J. Phys. Chem. A, 103, 6820 (1999). b) Z.-G.
Wang and G. B. Hammond, J. Org. Chem., 65, 6547 (2000). c)
P. L. Coe, J. Burdon, and I. B. Haslock, J. Fluorine Chem., 102, 43
(2000). d) A. Saito, M. Okada, Y. Nakamura, R. Aoki, H. Ito, A.
Horikawa, and T. Taguchi, The 24th Fluorine Conference of Japan,
Kyoto, September 2000, Abstr., No. O-27.
5
6
7
8
9
gem-Difluoroolefins are susceptible to nucleophilic substitution for
the vinylic fluorine via addition–elimination processes. The attack
of nucleophiles is governed to occur exclusively at the difluoro-
methylene carbon so that the fluorines are placed at the position ꢂto
the electron-rich carbon in the transition state to avoid electron-pair
repulsion.
‘‘Organofluorine Chemistry, Principles and Commercial Applica-
tions,’’ ed. by R. E. Banks, B. E. Smart, and J. C. Tatlow, Plenum
Press, New York (1994), p 57;V. J. Lee, ‘‘Conjugate Additions of
Reactive Carbanions to Activated Alkenes and Alkynes,’’ in
‘‘Comprehensive Organic Synthesis,’’ ed. by B. M. Trost, Perga-
mon Press, Oxford (1991), Vol. 4, p 69.
bearing no subutituents on the 4-position gave better results
(Entries 1 vs 4 and 3 vs 5). Concerning para-substituents on the 2-
phenyl group, electron-withdrawing and electron-donating
groups caused little effect on the cyclization (Entries 2, 3, and
5).14
The synthesis of 1-monofluorinated cycloalkenes is limited to the
following method via difluorination of cyclic ketones and
dehydrofluorination: D. R. Strobach and G. A. Boswell, Jr., J.
Org. Chem., 36, 818 (1971).
In conclusion, 5-endo-trig cyclizations of gem-difluoro-
olefins are successfully achieved by not only intramolecular
heteronucleophiles but also sp3 carbon nucleophiles, to which
much less attention has been paid in such ring closure. By this
carbocyclization, the scope of the intramolecular substitution of
gem-difluoroolefins has been expanded in terms of five-
membered ring formation.
10 J. Ichikawa, J. Fluorine Chem., 105, 257 (2000) and references
therein.
1
11 All new compounds were fully characterized by H, 19F, and 13
C
NMR, IR, MS, and combustion analysis (ꢃ0:3%) and/or HRMS.
12 W. F. Bailey and E. R. Punzalan, J. Org. Chem., 55, 5404 (1990);
E. Negishi, D. R. Swanson, and C. J. Rousset, J. Org. Chem., 55,
5406 (1990).
13 When 1,1-difluoro-2-phenyl-1-hexene was treated with butyl-
lithium (1.1 mol. amt.) under the same reaction conditions as those
for 4, the intermolecular substitution of the butyl group for the
vinylic fluorine occurred to give the E=Z mixture (E=Z ¼ 70=30) of
products in 69% yield.7
We dedicate this article to Professor Teruaki Mukaiyama on
the occasion of his 75th birthday.
References and Notes
1
14 1,1-Difluoro-2-(3-iodopropyl)-4-phenyl-1-pentene underwent no
cyclization on treatment with tert-butyllithium (2.2 mol. amt.)
under the same reaction conditions as those for 4.
J. E. Baldwin, J. Chem. Soc., Chem. Commun., 1976, 734;J. E.
Baldwin, J. Cutting, W. Dupont, L. Kruse, L. Silberman, and R. C.