Base-free Hiyama coupling reaction via a group 10 metal fluoride intermediate generated by C-F bond activation

Article abstract of DOI:10.1021/om5005513

A Pd(0)-catalyzed Hiyama coupling reaction of tetrafluoroethylene (TFE) proceeded without the use of a base to give α,β,β- trifluorostyrene derivatives. A Ni(0)-catalyzed Hiyama coupling reaction of perfluoroarenes also occurred without a base. The key intermediate in these reactions would be a transition-metal fluoride complex that is generated in situ by the oxidative addition of a C-F bond.

Full text of DOI:10.1021/om5005513

Communication
pubs.acs.org/Organometallics
Terms of Use
Base-Free Hiyama Coupling Reaction via a Group 10 Metal Fluoride
Intermediate Generated by C−F Bond Activation
Hiroki Saijo,† Hironobu Sakaguchi,† Masato Ohashi,† and Sensuke Ogoshi*,†,‡
†Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
‡JST, ACT-C, Suita, Osaka 565-0871, Japan
S
* Supporting Information
ABSTRACT: A Pd(0)-catalyzed Hiyama coupling reaction of
tetrafluoroethylene (TFE) proceeded without the use of a base
to give α,β,β-trifluorostyrene derivatives. A Ni(0)-catalyzed
Hiyama coupling reaction of perfluoroarenes also occurred
without a base. The key intermediate in these reactions would
be a transition-metal fluoride complex that is generated in situ
by the oxidative addition of a C−F bond.
mong the transition-metal-catalyzed C−C bond formation
reactivity toward organosilicon reagents. In fact, the trans-
Areactions, the Hiyama coupling reaction of organic halides metalation of a transition-metal fluoride complex with an
organosilicon reagent [XSiR3] (X = H, Cl, CF3, etc.) is a well-
established method for the synthesis of various kinds of
transition-metal complexes [LnTm-X].6 Although aryl group
transfer (X = Ar) has remained less developed due to the
relatively inert Si−C bond, Ball demonstrated the reaction of
(IPr)CuF with ArSi(OMe)3 for the synthesis of the
corresponding organocopper reagents.6d Against the aforemen-
tioned research backgrounds, we assumed that the Hiyama
coupling reaction via C−F bond activation could also proceed
without the use of a base, because the transition-metal fluoride
intermediate generated by the oxidative addition of a C−F
bond would be sufficiently reactive toward neutral organo-
silicon reagents (Scheme 1).
with organosilicon reagents has garnered a great deal of interest
in recent years, due to the ease of preparation, stability, and
environmentally benign nature of organosilicon reagents. Since
the pioneering works accomplished by Hiyama, several groups
have reported various modifications with functionalized
organosilicon reagents.1 These reactions generally require an
activator to enhance the reactivity of an organosilicon reagent,
which is achieved by the addition of a fluoride anion source
such as TBAF. Recent developments have made this reaction
possible with the aid of a Brønsted base instead of the fluoride
anion.1e,g,2 These methods are called “fluoride-free” Hiyama
coupling reactions and have attracted much attention for
decades. However, little is known about “base-free” Hiyama
coupling reactions. To the best of our knowledge, base-free
coupling reactions of organosilicon reagents have been achieved
only while using allylic carbonate or vinyl oxirane as a
substrate.3 These reactions would proceed via (η3-allyl)-
palladium alkoxide intermediates, which are considered to be
an activator for neutral organosilicon reagents. However, base-
free reactions using alkenyl or aryl halides as substrates have
not been reported, except for those using preliminarily activated
organosilicon reagents.4
Thus, the reactivity of trans-(PCy3)2Pd(F)(CF2CF) (1)
toward organosilicon reagents was examined. We previously
Scheme 1. Base-Free Hiyama Coupling Reaction via a
Transition-Metal Fluoride Key Intermediate
Our group has recently developed novel transformation
reactions via C−F bond activation.5 In 2013, we disclosed a
base-free Suzuki−Miyaura coupling reaction using either
fluoroalkenes or fluoroarenes.5b Although the Suzuki−Miyaura
coupling reaction also generally requires some base as an
activator, our reactions proceeded smoothly in the absence of
any base. This is because the transition-metal fluoride key
intermediate [LnTm-F], which is generated by the oxidative
addition of a C−F bond, is reactive enough to undergo the
transmetalation with neutral organoboron compounds. Also,
transition-metal fluoride complexes are considered to have high
Received: May 21, 2014
Published: July 15, 2014
© 2014 American Chemical Society
3669
dx.doi.org/10.1021/om5005513 | Organometallics 2014, 33, 3669−3672

Organometallics
Communication
reported that 1 was generated by the oxidative addition of a C−
F bond of tetrafluoroethylene (TFE) by heating at 100 °C.5b In
the presence of dibenzylideneacetone (DBA), the reaction of 1
with an excess amount of PhSi(OMe)3 occurred at 100 °C to
give α,β,β-trifluorostyrene (2a) in 50% yield (Scheme 2). It
Scheme 2. Reactivity of 1 toward PhSi(OMe)3
Figure 1. Comparison between the reaction rates in the absence (A,
blue) and presence (B, red) of 10 mol % of FSi(OEt)3. The reactions
were monitored by means of 19F NMR spectroscopy. Conditions:
PhSi(OMe)3 (0.10 mmol), TFE (3.5 atm, >3.0 equiv),
Pd2(dba)3(C6H6) (0.0025 mmol), PCyp3 (0.005 mmol),THF-d8 (0.6
mL) at 100 °C.
would be the result of transmetalation of PhSi(OMe)3 with 1,
followed by reductive elimination. Undesired trifluoroethylene
(3) was also observed in 35% yield, which would be generated
via methoxy group transfer, followed by β-hydride elimination
and reductive elimination.7,8 In contrast, the corresponding
palladium chloride (4a), bromide (4b), and iodide (4c) did not
react with PhSi(OMe)3 at all under the same reaction
conditions. These results indicated that the fluoropalladium
complex is reactive enough toward neutral organosilicon
compounds, and that a fluorine atom bound to palladium
plays an essential role in this transmetalation reaction.
in situ as the coupling reaction proceeded. By using 10 mol %
of FSi(OEt)3 as an additive, the reaction was obviously
accelerated (Figure 1B), and the yield of 2a was increased to
91% (Table 1, run 3).11 We attempted to uncover the
acceleration mechanism, but it remains unclear. In contrast,
when TBAF was used as an additive, the coupling reaction did
not proceed at all (run 4). In this case, pentafluoroethane was
obtained as a result of the addition reaction of a fluoride anion
toward TFE.12 This compound was not observed when the
base-free coupling proceeded successfully (for example, runs
1−3). These results indicated that free fluoride anion would not
be involved in the base-free coupling reaction. The catalytic
reaction also did not proceed when lithium iodide (LiI) was
used as an additive, because the fluorine atom cleaved from
TFE formed stable and insoluble lithium fluoride (run 5).5a,e
With the optimized reaction conditions established, we
explored the scope of the reaction with respect to arylsiloxanes
(Table 2). In the presence of 2.5 mol % of Pd2(dba)3(C6H6), 5
mol % of PCyp3, and 10 mol % of FSi(OEt)3, the coupling
reaction of TFE with PhSi(OMe)3 occurred at 80 °C to give 2a
in 94% yield, although an attempt to isolate 2a failed due to its
high volatility. The reaction using sterically hindered
trimethoxy(naphthalen-1-yl)silane also proceeded, and the
corresponding coupling product (2b) was isolated in 72%
yield. Trimethoxy(naphthalen-2-yl)silane and (1,1′-biphenyl-4-
yl)trimethoxysilane were converted into the corresponding
trifluorostyrene derivatives (2c,d) in 71% and 50% yields,
respectively. The reaction using electron-rich trimethoxy(4-
methoxyphenyl)silane required high catalyst loading to furnish
2e in 57% yield. Electron-deficient trimethoxy(4-
(trifluoromethyl)phenyl)silane was smoothly converted into
2f in 75% yield. The reactions using arylsiloxanes bearing a C−
F bond on the aromatic ring gave the corresponding coupling
products in high yields (2g,h). C−Cl bonds on the aromatic
ring and ester group were tolerated in the reaction (2i,j). An
alkenylsiloxane was also applicable to this coupling reaction
(2k).
Encouraged by the results of the stoichiometric reactions, we
developed a Pd(0)-catalyzed base-free coupling reaction of TFE
with PhSi(OMe)3 (Table 1).9,10 Reactions were conducted in a
a
Table 1. Pd(0)-Catalyzed Coupling Reaction of TFE
run ligand (amt (mol %))
additive (amt)
none
time (h) yield (%)
1
2
3
4
5
PCy3 (10)
PCyp3 (5)
PCyp3 (5)
PCyp3 (5)
PCyp3 (5)
25
4
73
76
91
0
none
FSi(OEt)3 (10 mol %)
TBAF (1 equiv)
LiI (1 equiv)
6
6
6
0
a
Yields were determined by 19F NMR with PhCF3 as an internal
standard.
pressure-tight NMR tube and were monitored by 19F NMR
analysis. In the presence of 2.5 mol % of Pd2(dba)3(C6H6) and
10 mol % of PCy3, the reaction of PhSi(OMe)3 with TFE
proceeded at 100 °C to afford 2a in 73% yield without the use
of either a fluoride anion or a Brønsted base (run 1). After a
series of surveys of the reaction conditions, we found that a
reaction using 5 mol % of PCyp3 (Cyp = c-C5H9) as a ligand
was faster than that using PCy3 (run 2; see also the Supporting
Information). In these catalytic reactions, only a small amount
(∼10%) of trifluoroethylene 3 was observed, unlike the case for
the stoichiometric reaction shown in Scheme 2. The time−
product yield curve of this catalytic reaction resembled that
observed for an autocatalytic reaction (Figure 1A). The
generation rate of 2a was slow at the early stage of the
reaction and then increased sharply at some point. We assumed
the increase was caused by the fluorosilanes that were generated
Furthermore, we expanded this base-free method to the
coupling reaction of fluoroarenes. Our previous study showed
that the Suzuki−Miyaura coupling reaction of fluoroarenes
proceeded under base-free conditions using the NHC-
coordinated Ni(0) complex [Ni2(iPr2Im)4(COD)] that was
developed by Radius.5b,13 They reported the efficient oxidative
3670
dx.doi.org/10.1021/om5005513 | Organometallics 2014, 33, 3669−3672

Organometallics
Communication
a
methoxyheptafluorotoluene was also observed as a side-reaction
product, as a result of the methoxy group transfer.15
Table 2. Scope of the Reaction Involving TFE
Next we investigated the scope of the Ni(0)-catalyzed base-
free Hiyama coupling reaction (Table 4). The reaction of 5
a
Table 4. Scope of the Reaction Involving Fluoroarenes
a
Isolated yields. The yields in parentheses are NMR yields determined
b
by 19F NMR with PhCF3 as an internal standard. Heated to 80 °C.
a
Isolated yields. The yield in parentheses is the NMR yield determined
c
by 19F NMR with PhCF3 as an internal standard.
Conducted with 5 mol % of Pd2(dba)3(C6H6), 10 mol % of PCyp3,
and 20 mol % of FSi(OEt)3.
addition of an Ar−F bond when using this complex to form
[(iPr2Im)2Ni(F)(Ar)].13b,d This type of fluoronickel complex
would be a key intermediate in our base-free Suzuki−Miyaura
coupling reaction and would be expected to play the same role
in the base-free Hiyama coupling reaction.
We examined the reaction conditions in the model reaction
of octafluorotoluene (5) with PhSi(OMe)3 (Table 3). The
with trimethoxy(4-methoxyphenyl)silane gave the coupling
product 6b in 74% isolated yield. Moreover, electron-deficient
arylsiloxanes bearing a trifluoromethyl or fluorine group were
converted into the corresponding biaryls in excellent yields
(6c,d). In these reactions, the formation of 4-methoxyhepta-
fluorotoluene could not be avoided, but it could be easily
separated by means of silica gel column chromatography. In
addition, the coupling reaction of hexafluorobenzene (7) with
arylsiloxanes also proceeded in the absence of any base to give
the corresponding biaryls in moderate yields (8a,b,d). The
reaction using trimethoxy(4-(trifluoromethyl)phenyl)silane
afforded 8c in only 15% yield, and substantial amounts of
unreacted starting materials were recovered.
a
Table 3. Ni(0)-Catalyzed Hiyama Coupling Reaction of 5
Although the mechanistic details of the base-free Hiyama
coupling reaction have not been fully revealed at this time, on
the basis of the stoichiometric reaction shown in Scheme 2,
there is no doubt that metal fluoride complexes play a crucial
role. We ruled out the mechanism involving free fluoride anion,
because the coupling reaction of TFE did not proceed at all
when TBAF was added. Fluorosilanes accelerated the Pd(0)-
catalyzed Hiyama coupling reaction of TFE, but it would not be
necessary for the base-free mechanism. We considered the
possibility that fluorosilanes would facilitate the oxidative
addition of a C−F bond of TFE toward Pd(0), which seems
to be an inefficient step in the absence of a Lewis acidic
species.14 This is consistent with the fact that fluorosilanes did
not affect the Ni(0)-catalyzed Hiyama coupling reaction of
fluoroarenes, because [Ni2(iPr2Im)4(COD)] is highly efficient
in the oxidative addition of a C−F bond on fluoroarenes
without the aid of a Lewis acidic additive.13
additive (amt (mol
%))
yield
(%)
run
catalyst (amt (mol %))
1
2
3
Pd2(dba)3(C6H6) (2.5), PCyp3 (5)
[Ni2(iPr2lm)4(COD)] (5)
[Ni2(iPr2lm)4(COD)] (5)
FSi(OEt)3 (10)
none
0
99
95
FSi(OEt)3 (10)
a
Yields were determined by 19F NMR with PhCF3 as an internal
standard.
Pd(0)/PCyp3 catalyst did not work at all in the reaction (run
1), since the oxidative addition of a C−F bond to Pd(0) did not
occur.5d,14 On the other hand, in the presence of 5 mol % of
[Ni2(iPr2Im)4(COD)], the base-free reaction proceeded to
afford 4-phenylheptafluorotoluene (6a) in excellent yield (run
2). Unlike the case of the reaction using TFE as a substrate,
neither the reaction rate nor the yield of 6a was improved by
the addition of FSi(OEt)3 (run 3). In this reaction, undesired 4-
3671
dx.doi.org/10.1021/om5005513 | Organometallics 2014, 33, 3669−3672

Organometallics
Communication
Radius, U. Eur. J. Inorg. Chem. 2008, 2680. (c) Klinkenberg, J. L.;
Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 5758. (d) Herron, J. R.;
Ball, Z. T. J. Am. Chem. Soc. 2008, 130, 16486. (e) Herron, J. R.;
Russo, V.; Valente, E. J.; Ball, Z. T. Chem. Eur. J. 2009, 15, 8713.
(f) Russo, W.; Herron, J. R.; Ball, Z. T. Org. Lett. 2010, 12, 220.
(7) When using PhSi(OEt)3 instead of PhSi(OMe)3, we detected
acetaldehyde by means of 1H NMR. It indicated that β-hydrogen
elimination took place.
In summary, we developed a novel base-free Hiyama
coupling reaction of either TFE or fluoroarenes via C−F
bond activation. In the reaction involving TFE, fluorosilanes
accelerated the catalytic reaction. Metal fluoride complexes
generated in situ by the oxidative addition of a C−F bond
played an essential role in the base-free reaction. Further
investigation into the mechanistic details is now ongoing.
(8) Alkoxy group transfer from RSi(OMe)3 has been reported in
some papers; see: (a) Yamasaki, S.; Fujii, K.; Wada, R.; Kanai, M.;
Shibasaki, M. J. Am. Chem. Soc. 2002, 124, 6536. (b) Tomita, D.;
Wada, R.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2005, 127, 4138.
(c) Milton, E. J.; Fuentes, J. A.; Clarke, M. L. Org. Biomol. Chem. 2009,
7, 2645. (d) Wang, T.; Love, J. A. Synthesis 2007, 15, 2237.
(e) Buckley, H. L.; Wang, T.; Tran, O.; Love, J. A. Organometallics
2009, 28, 2356. (f) Keyes, L.; Sun, A. D.; Love, J. A. Eur. J. Org. Chem.
2011, 3985. (g) Bhadra, S.; Dzik, W. I.; Goossen, L. J. J. Am. Chem.
Soc. 2012, 134, 9938.
ASSOCIATED CONTENT
* Supporting Information
Text, figures, and tables giving detailed experimental
procedures and analytical and spectral data for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail for S.O.: ogoshi@chem.eng.osaka-u.ac.jp.
Notes
■
(9) See the Supporting Information for details of the optimization of
the reaction conditions.
(10) We assumed that the oligomerization of trifluorostyrene might
occur, although no practical evidence was obtained. We did not detect
a significant amount of potential further reaction products, including
difluorodiphenylethyrene, difluorostyrene, and 1,2,3,3,4,4-hexafluoro-
1,2-diphenylcyclobutane.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank Prof. Udo Radius and David Schmidt (Julius-
■
(11) We did not use FSi(OMe)3 but rather FSi(OEt)3, because the
latter is commercially available.
Maximilians-Universitat Wurzburg) for the gift of
̈
̈
[Ni2(iPr2Im)4(COD)]. This work was partially supported by
a Grant-in-Aid for Scientific Research (A) (No. 21245028), a
Grant-in-Aid for Young Scientists (A) (No. 25708018), and a
Grant-in-Aid for Scientific Research on Innovative Areas
“Molecular Activation Directed toward Straightforward Syn-
thesis” (No. 23105546) from the MEXT and by the Adaptable
and Seamless Technology transfer program through target
driven R&D (A-STEP; No. AS2525804M) from the JST. M.O.
also acknowledges The Noguchi Institute.
(12) The hydrogen source is residual water in the solvent or in the
solution of TBAF (1.0 M in THF). This kind of addition reaction is
found to occur even in the absence of palladium and/or organosilicon
reagent, due to the highly nucleophilic nature of TFE.
(13) (a) Schaub, T.; Radius, U. Chem. Eur. J. 2005, 11, 5024.
(b) Schaub, T.; Backes, M.; Radius, U. J. Am. Chem. Soc. 2006, 128,
15964. (c) Schaub, T.; Fischer, P.; Steffen, A.; Braun, T.; Radius, U.;
Mix, A. J. Am. Chem. Soc. 2008, 130, 9304. (d) Schaub, T.; Fischer, P.;
Meins, T.; Radius, U. Eur. J. Inorg. Chem. 2011, 3122. (e) Fischer, P.;
Gotz, K.; Eichhorn, A.; Radius, U. Organometallics 2012, 31, 1374.
̈
(14) It is generally known that the oxidative addition of an Ar−F
bond to Pd(0) is hard to carry out. Grushin reported that the reaction
of C6F6 with Pd(PCy3)2 in THF at 70 °C afforded [(PCy3)2Pd(F)
(C6F5)] in only 3% yield; see: Macgregor, S. A.; Roe, D. C.; Marshall,
W. J.; Bloch, K. M.; Bakhmutov, V. I.; Grushin, V. V. J. Am. Chem. Soc.
2005, 127, 15304 See also Ref5e.
(15) A possible pathway for the methoxy group transfer is SNAr type
substitution on [LnNi(F)(C7F7)] by activated ArSi(OMe)3 via a five-
membered intermediate.
REFERENCES
■
(1) (a) Hatanaka, Y.; Hiyama, T. Tetrahedron. Lett. 1988, 1, 97.
(b) Hiyama, T. J. Organomet. Chem. 2002, 653, 58. (c) Tamao, K.;
Kobayashi, K.; Ito, Y. Tetrahedron. Lett. 1989, 44, 6051. (d) Denmark,
S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121, 5821. (e) Denmark, S. E.;
Sweis, R. F. J. Am. Chem. Soc. 2001, 123, 6439. (f) Itami, K.; Kamei, T.;
Yoshida, J. J. Am. Chem. Soc. 2003, 125, 14670. (g) Nakao, Y.;
Imanaka, H.; Sahoo, A. K.; Yada, A.; Hiyama, T. J. Am. Chem. Soc.
2005, 127, 6952.
(2) (a) Hagiwara, E.; Gouda, K.; Hatanaka, Y.; Hiyama, T.
Tetrahedron. Lett. 1997, 3, 439. (b) Hirabayashi, K.; Kawashima, J.;
Nishihara, Y.; Mori, A.; Hiyama, T. Org. Lett. 1999, 1, 299.
(c) Hirabayashi, K.; Mori, A.; Kawashima, J.; Suguro, M.; Nishihara,
Y.; Hiyama, T. J. Org. Chem. 2000, 65, 5342.
(3) (a) Matsuhashi, H.; Hatanaka, Y.; Kuroboshi, M.; Hiyama, T.
Tetrahedron Lett. 1995, 9, 1539. (b) Matsuhashi, H.; Asai, S.;
Hirabayashi, K.; Hatanaka, Y.; Mori, A.; Hiyama, T. Bull. Chem. Soc.
Jpn. 1997, 70, 1943.
(4) (a) Brescia, M.-R.; DeShong, P. J. Org. Chem. 1998, 63, 3156.
(b) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 3266.
(c) Denmark, S. E.; Baird, J. D. Org. Lett. 2006, 8, 703. (d) Denmark,
S. E.; Kallemeyn, J. M. J. Am. Chem. Soc. 2006, 123, 15958.
(5) (a) Ohashi, M.; Kambara, T.; Hatanaka, T.; Saijo, H.; Doi, R.;
Ogoshi, S. J. Am. Chem. Soc. 2011, 133, 3256. (b) Ohashi, M.; Saijo,
H.; Shibata, M.; Ogoshi, S. Eur. J. Org. Chem. 2013, 443. (c) Ohashi,
M.; Shibata, M.; Saijo, H.; Kambara, T.; Ogoshi, S. Organometallics
2013, 32, 3631. (d) Ohashi, M.; Kamura, R.; Doi, R.; Ogoshi, S. Chem.
Lett. 2013, 42, 933. (e) Ohashi, M.; Doi, R.; Ogoshi, S. Chem. Eur. J.
2014, 20, 2040.
(6) For selected recent examples, see: (a) Grushin, V. V.; Marshall,
W. J. J. Am. Chem. Soc. 2006, 128, 12644. (b) Schaub, T.; Backes, M.;
3672
dx.doi.org/10.1021/om5005513 | Organometallics 2014, 33, 3669−3672