988
In conclusion, we have disclosed a facile approach to ¢,¢-
10 For a recent review on the Negishi coupling, see: E.-i. Negishi,
Q. Hu, Z. Huang, M. Qian, G. Wang, Aldrichimica Acta 2005,
38, 71.
11 H. Schumann, S. Freitag, F. Girgsdies, H. Hemling, G.
cited therein.
difluorostyrenes from 1,1-difluoroethylene via the palladium-
catalyzed coupling of the thermally stable 2,2-difluorovinylzinc
chloride-TMEDA complex 2a. The high functional group toler-
ance and the elegant chemoselectivity of the reaction would
facilitate the construction of a library of various ¢,¢-difluorosty-
renes. The zinc-TMEDA complex 2a has proven to be storable,
and thus is an excellent reagent for introducing the difluorovinyl
group.
12 An equimolar amount of TMEDA could not complete the
complexation.
13 The formation of 2a was supported by the 19F NMR (470
MHz) spectra of the reaction mixture. The data are shown
below (¤: parts per million from hexafluorobenzene). 2a: ¤
This research was supported in part by Grant-in-Aid for
Scientific Research from MEXT, Japan. We acknowledge Central
Glass Co., Ltd. for the generous gift of 1,1-difluoroethylene.
87.9 (1F, dd, JFF = 58 Hz, JFH = 58 Hz), 98.7 (1F, dd, JFF
=
58 Hz, JFH = 15 Hz). cf. 2,2-Difluorovinylzinc chloride: ¤ 86.2
(1F, dd, JFF = 55 Hz, JFH = 55 Hz), 98.5 (1F, dd, JFF = 55 Hz,
J
FH = 14 Hz). 1,1-Difluoroethylene: ¤ 80.0-80.2 (m).
This paper is in celebration of the 2010 Nobel Prize awarded
to Professors Richard F. Heck, Akira Suzuki, and Ei-ichi Negishi.
14 To a solution of TMEDA (98 ¯L, 0.65 mmol) in THF (2.0 mL)
and diethyl ether (0.50 mL) at ¹110 °C was slowly added
gaseous 1,1-difluoroethylene (14.5 mL, 0.60 mmol) via sy-
ringe, and the mixture was stirred at the same temperature for
5 min. To the solution at ¹110 °C was slowly added s-BuLi
(0.96 M in hexane, 0.52 mL, 0.50 mmol) and the mixture was
stirred at the same temperature for 20 min. To the reaction
mixture at ¹110 °C was added a THF solution of anhydrous
ZnCl2 (1.00 M, 0.50 mL, 0.50 mmol). After the reaction
mixture was stirred at ¹100 °C for 30 min, a THF-ether
solution of 2a was obtained as a colorless solution (0.48 mmol,
95%: The yield and the concentration were determined by
19F NMR using PhCF3 as an internal standard).
15 In a two-necked flask was placed the prepared THF-ether
solution of 2a (0.125 M, 7.6 mL, 0.95 mmol). To the solution
were added a solution of 4-iodoanisole (3b, 189 mg, 0.81
mmol) in THF (1.5 mL) and [Pd(PPh3)4] (17 mg, 15 ¯mol).
After refluxing for 6 h, the reaction mixture was filtered
through a pad of silica gel (diethyl ether). The filtrate was
concentrated under reduced pressure and purified by prepar-
ative thin layer chromatography (silica gel, pentane:diethyl
ether = 20:1) to give 4b (119 mg, 87%) as a colorless liquid.
16 Difluorostyrene 4a was difficult to isolate in high yield because
of its volatility. Difluorostyrene 4i and unreacted iodide 3i
were inseparable by distillation and column chromatography.
17 PEPPSI-IPr is known as an efficient catalyst for the Negishi
coupling. For reviews, see: a) M. G. Organ, S. Avola, I.
Dubovyk, N. Hadei, E. A. B. Kantchev, C. J. O’Brien, C.
2768. c) C. Valente, M. E. Belowich, N. Hadei, M. G. Organ,
References and Notes
1
K. Uneyama, Organofluorine Chemistry, Blackwell Publish-
ing, Oxford, UK, 2006, Chap. 1, pp. 60-67; K. Uneyama,
Organofluorine Chemistry, Blackwell Publishing, Oxford, UK,
2006, Chap. 2, pp. 112-121.
2
3
a) S. A. Fuqua, W. G. Duncan, R. M. Silverstein, J. Org.
Silverstein, Org. Synth. Coll. Vol. 1973, 5, 390. c) S.-i.
Hayashi, T. Nakai, N. Ishikawa, D. J. Burton, D. G. Naae, H.
Bhadury, M. Palit, M. Sharma, S. K. Raza, D. K. Jaiswal, J.
4
a) J. Ichikawa, M. Fujiwara, H. Nawata, T. Okauchi, T.
5
6
T. M. Gøgsig, L. S. Søbjerg, A. T. Lindhardt, K. L. Jensen,
For other approaches to ¢,¢-difluorostyrene, see: a) V. G.
Nenajdenko, G. N. Varseev, V. N. Korotchenko, A. V. Shastin,
126, 1361. c) M. Pohmakotr, K. Boonkitpattarakul, W.
Ieawsuwan, S. Jarussophon, N. Duangdee, P. Tuchinda, V.
18 Cy-JohnPhos is a Buchwald ligand, which is used for various
coupling reactions of sterically hindered substrates. For a
19 For several examples on chemoselective coupling reactions,
7
8
9
Fluoroacetylenes have been prepared by lithiation of 1,1-
difluoroethylene. See: T. Hanamoto, Y. Koga, T. Kawanami, H.
Without any lithium salts, fluoroacetylenes are hardly pro-
duced from 2,2-difluorovinylzinc species. See ref. 4.
Chem. Lett. 2011, 40, 986-988
© 2011 The Chemical Society of Japan