Pd(OAc)2 catalyzed olefination of highly electron-deficient perfluoroarenes

Article abstract of DOI:10.1021/ja908434e

An efficient, Pd(OAc)₂ catalyzed method for direct olefination of highly electron-deficient perfluoroarenes was developed. The reaction scope includes a series of activated and nonactivated alkenes in moderate to high yields with moderate to high regio- and stereoselectivities.

Full text of DOI:10.1021/ja908434e

Published on Web 03/12/2010
Pd(OAc)2 Catalyzed Olefination of Highly Electron-Deficient Perfluoroarenes
Xingang Zhang,* Shilu Fan, Chun-Yang He, Xiaolong Wan, Qiao-Qiao Min, Jie Yang, and
Zhong-Xing Jiang
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Road, Shanghai 200032, China
Received June 29, 2009; E-mail: xgzhang@mail.sioc.ac.cn
Perfluoroarenes constitute a distinct class of fluorinated com-
pounds due to their importance in materials and life science.1
Usually, they can be prepared from perfluoroaryl metals, halides,
or aldehydes.1d,2 However, this “prefunctionalization” process has
intrinsic drawbacks in terms of atom and step economy. Recently,
the direct arylation, alkenylation and alkylation of perfluoroarenes
were reported by Fagnou,3 Daugulis,4 and Nakao and Hiyama,5
respectively. While, these approaches are attractive, new methods
for the direct alkenylation of perfluoroarenes remain highly desirable
in view of the requirement of alkenyl halides as substrates4 or
employment of an air-sensitive Ni(0) catalyst that is only suitable
for internal alkynes in this process5 in these prior studies. However,
unlike the direct olefination of electron-rich arenes,6-8 reactions
of electron-deficient arenes are still a great challenge, and only rare
examples have been reported.9 The reason is that the electron-
deficient arenes are nonreactive due to their poor coordination with
Pd(OAc)2.9a,d In addition, the σ-bonds between transition metals
and perfluorinated groups, such as the highly electron-deficient
pentafluorophenyl group (M-C6F5), are particularly strong and
reluctant to reaction.2c,d,10 Pioneering work on insertion of alkenes
into the M-C6F5 bond using catalytic (NBu4)2[Pd2-(µ-
Br)2(C6F5)2Br2] has been reported by Espinet and Milstein and
co-workers.2c,d This work represents an impressive example of
transition metal catalysis to access organofluorine compounds, but
fluorinated arylhalides were required and nonactivated alkenes such
as aliphatic and electron-rich alkenes were less promising substrates.
Herein, we report a first example of Pd(OAc)2 catalyzed direct
olefination of highly electron-deficient perfluoroarenes with a broad
range of substrates in moderate to high yields and with moderate
to high stereo- and regioselectivities.
4). Acrylonitrile 2g was also tolerated, and a 34% yield of a mixture
(E/Z ) 1.4:1) of isomers of 3g was provided (entry 7). Notably,
the nonactivated aliphatic olefins 2k-l underwent smooth reactions
in good yields (entries 11-12), which is in sharp contrast to
previous results.2c,d Moreover, electron-rich alkenes were readily
reacted with 1 in good yields (entries 13-15). For 2o, a mixture
of constitutional isomers 3o and 4o were formed (entry 15).
Table 1. Oxidative Olefination of Pentafluorobenzene with Various
Alkenesa
Initially, a highly electron-deficient pentafluorobenzene 1 and
ethyl acrylate 2a were chosen as model substrates for this study.
After a survey of reaction conditions we found that the solvent,
oxidants, and Pd catalysts are critical for the reaction efficiency
(see Supporting Information). A mixed solvent system of 5%
DMSO in DMF was found to be the optimum reaction medium.
The reaction carried out with 1 (1 equiv), 2a (2 equiv), and Ag2CO3
(2 equiv) which functions as both a base and oxidant in the presence
of Pd(OAc)2 (10 mol %) at 120 °C provided 3a in good yield (78%,
mixture of E/Z isomers, E/Z ) 14:1). Other oxidants such as
Cu(OAc)2, oxone, BQ, PhI(OAc)2, and O2 or other Pd catalysts
(PdCl2, Pd(TFA)2, and Pd2(dba)3) showed less or no activity.
A great variety of pentafluorophenyl substituted alkenes can be
generated via this method (Table 1). The alkenylation of 1 worked
well for electron-deficient olefins bearing ester, amide, phosphonate,
or ketone groups, and moderate to excellent yields and high
stereoselectivities were obtained (entries 1-6, 8-10). For some
entries, removal of the minor Z-isomer required reversed-phase
preparative HPLC. Interestingly, in the case of branched olefin 2d,
constitutional isomer 4d was obtained as the major product (entry
a Reaction conditions unless otherwise specified: 1 (0.6 mmol), 2
(2.0-3.0 equiv), and DMF (2.4 mL) + DMSO (120 µL) for 10-12 h.
b Isolated yield. c Yield after purification by reversed-phase preparative
HPLC. d Determined by 19F NMR. e Using 20 mol % Pd(OAc)2, 3.0
equiv of Ag2CO3 for 12-24 h. f Using 20 mol % Pd(OAc)2, 3.0 equiv
of Ag2CO3, and 4.0 equiv of alkene. g Isolated yield of mixtures of
constitutional isomers (see Supporting Information).
9
4506 J. AM. CHEM. SOC. 2010, 132, 4506–4507
10.1021/ja908434e  2010 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Formation of Bis(alkenyl)perfluoroarenes
The substrate scope with respect to fluoroarenes was also tested,
and representative results are summarized in Table 2.11 We found
that using 10 mol % of Pd(OAc)2, 1.2 equiv of PivOH12 instead of
DMSO (5%), and 4.0 equiv of fluoroarenes afforded alkenylated
products in moderate yields with moderate to good regioselectivities
(for details see Supporting Information). Generally, the reaction
with electron-rich alkene 2m afforded higher yields than that of
electron-deficient alkene 2c. The most acidic C-H bonds located
between two fluorines (entries 1-2, 4-5) are primary reaction sites
and provided mostly monoalkenylated products in higher yields
than substrates with C-H bonds ortho to only one fluorine, such
as 1,2,3,4-tetrafluorobenzene (entry 3). However, in the monoalk-
enylation of 1,2-difluorobenzene to give 5fa or 5fb, a decreased
regioselectivity between position a (5faa or 5fba) and position b
(5fab or 5fbb) was observed (5faa/5fab ) 2:1, 5fba/5fbb ) 2:1)
(entry 6). It is worth noting that an arylbromide was also tolerated
by the reaction conditions (entry 7) providing opportunities for
further functionalization. Furthermore, substrates with an electron-
donating methoxy group and fluorinated pyridine also furnished
the alkenylated products in moderate to good yields (entries 8-9).
was also performed in good yield (71%), indicating the good
reliability of the process (see Supporting Information).
In conclusion, we developed an efficient, Pd(OAc)2 catalyzed
method for direct olefination of highly electron-deficient perfluo-
roarenes. The reaction scope includes both activated and nonacti-
vated alkenes. Applications of alkenylated perfluoroarenes in design
and synthesis of bioactive molecules are under active investigation
in our laboratory.
Acknowledgment. NSF of China (20902100, 20852003,
20832008), the Shanghai Rising-Star Program (09QA1406900), and
SIOC are greatly acknowledged for funding this work. Professor
Wilfred A. van der Donk at UIUC and Professor Feng-Ling Qing
at SIOC are greatly acknowledged for their help.
Table 2. Oxidative Olefination of Fluoroarenes with Alkenesa
Supporting Information Available: Detailed experimental proce-
dures and characterization data for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
References
(1) For selected recent reviews, see: (a) Meyer, E. A.; Castellano, R. K.;
Diederich, F. Angew. Chem., Int. Ed. 2003, 42, 1210. (b) Mu¨ller, K.; Faeh,
C.; Diederich, F. Science 2007, 317, 1881. (c) Purser, S.; Moore, P. R.;
Swallow, S.; Gouverneur, V. Chem. Soc. ReV. 2008, 37, 320. (d) Amii,
H.; Uneyama, K. Chem. ReV. 2009, 109, 2119.
(2) For selected papers, see: (a) Harper, R. J., Jr.; Soloski, E. J.; Tamborski,
C. J. Org. Chem. 1964, 29, 2385. (b) Shen, Y.; Xiang, Y. Synth. Commun.
1991, 21, 1403. (c) Albe´niz, A. C.; Espinet, P.; Martn-Ruiz, B.; Milstein,
D. J. Am. Chem. Soc. 2001, 123, 11504. (d) Albe´niz, A. C.; Espinet, P.;
Mart´ın-Ruiz, B.; Milstein, D. Organometallics 2005, 24, 3679.
(3) (a) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem.
Soc. 2006, 128, 8754. (b) Lafrance, M.; Shore, D.; Fagnou, K. Org. Lett.
2006, 8, 5097.
(4) (a) Do, H.-Q.; Daugulis, O. J. Am. Chem. Soc. 2008, 130, 1128. (b) Do,
H.-Q.; Khan, R. M. K.; Daugulis, O. J. Am. Chem. Soc. 2008, 130, 15185.
(5) Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc.
2008, 130, 16170.
(6) (a) Moritani, I.; Fujiwara, Y. Tetrahedron Lett. 1967, 8, 1119. (b) Jia, C.;
Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara, Y. Science 2000,
287, 1992.
(7) For recent directed olefination of arenes, see: (a) Zaitsev, V. G.; Daugulis,
O. J. Am. Chem. Soc. 2005, 127, 4156. (b) Cai, G.; Fu, Y.; Li, Y.; Wan,
X.; Shi, Z. J. Am. Chem. Soc. 2007, 129, 7666. (c) Wang, J.-R.; Yang,
C.-T.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2007, 48, 5449. (d) Li, J.-J.;
Mei, T.-S.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47, 6452. (e) Houlden,
C. E.; Bailey, C. D.; Ford, J. G.; Gagne´, M. R.; Lloyd-Jones, G. C.; Booker-
Milburn, K. I. J. Am. Chem. Soc. 2008, 130, 10066.
(8) For recent olefination of indoles, see: (a) Ferreira, E. M.; Stoltz, B. M.
J. Am. Chem. Soc. 2003, 125, 9578. (b) Ma, S.; Yu, S. Tetrahedron Lett.
2004, 45, 8419. (c) Liu, C.; Widenhoefer, R. A. J. Am. Chem. Soc. 2004,
126, 10250. (d) Grimster, N. P.; Gauntlett, C.; Godfrey, C. R. A.; Gaunt,
M. J. Angew. Chem., Int. Ed. 2005, 44, 3125.
a Fluoroarene (4.0 equiv), 2 (0.6 mmol), DMF (2.4 mL) for 18-24 h.
b Isolated yield. c 5% DMSO was used instead of PivOH. d Isolated
yield of mixtures of regioisomers, number in parentheses is the
(9) For direct olefination of electron-deficient arenes or heterocycles without
directing group, see: (a) Zhang, Y.-H.; Shi, B.-F.; Yu, J.-Q. J. Am. Chem.
Soc. 2009, 131, 5072. (b) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am. Chem.
Soc. 2008, 130, 9254. (c) Wu, J.; Cui, X.; Chen, L.; Jiang, G.; Wu, Y.
J. Am. Chem. Soc. 2009, 131, 13888. For olefination of electron-deficient
arenes via activation of C-Si bond, see: (d) Rauf, W.; Thompson, A. L.;
Brown, J. M. Chem. Commun. 2009, 3874. For olefination of electron-
deficient arenes via decarboxylation, see: (e) Myers, A. G.; Tanaka, D.;
Mannion, M. R. J. Am. Chem. Soc. 2002, 124, 11250.
(10) (a) Clot, E.; Me´gret, C.; Eisenstein, O.; Perutz, R. N. J. Am. Chem. Soc.
2009, 131, 7817. (b) Evans, M. E.; Burke, C. L.; Yaibuathes, S.; Clot, E.;
Eisenstein, O.; Jones, W. D. J. Am. Chem. Soc. 2009, 131, 13464.
(11) Despite extensive attempts, we have been unable to improve the yields
and selectivity in Table 2.
regioselectivity between position
a
and position (b+c) or b.
e Fluoroarene (1.0 equiv), 2 (3.0 equiv), DMF (2.4 mL) + DMSO (5%).
f Pd(OAc)2 (15 mol %). g Purified by reversed-phase preparative HPLC;
number in parentheses is the ratio of E/Z. h Fluoroarene (1.0 equiv), 2
(3.0 equiv), DMF (2.4 mL), PivOH (1.2 equiv). i Pd(OAc)2 (20 mol %),
PivOH (3.0 equiv).
It was also possible to further derivatize the perfluoroarylated
alkenes through C-H functionalization. As depicted in Scheme 1,
compound 5ba reacted with 2f or 2 m, respectively, to form
unsymmetrical bis-alkenylated products 7 in good yields. This
strategy thus allows the selective installation of substituents at
different positions and provides access to highly functionalized
perfluoroarenes by catalytic methods. A 2-g-scale synthesis of 3a
(12) (a) Lafrance, M.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 16496. (b)
Lafrance, M.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2007, 129,
14570.
JA908434E
9
J. AM. CHEM. SOC. VOL. 132, NO. 13, 2010 4507