Synthesis of trifluorostyrene derivatives by palladium-catalyzed cross-coupling of lithium trimethoxy(trifluorovinyl)borate with aryl bromides

Article abstract of DOI:10.1002/chem.201103067

Fluor-ing it: The stable, crystalline trimethoxy(trifluorovinyl)borate is a convenient reagent for efficiently displacing a bromine atom with a trifluorovinyl group (see scheme). This Suzuki coupling reaction significantly simplifies the route to trifluor

Full text of DOI:10.1002/chem.201103067

COMMUNICATION
DOI: 10.1002/chem.201103067
Synthesis of Trifluorostyrene Derivatives by Palladium-Catalyzed Cross-
Coupling of Lithium Trimethoxy(trifluorovinyl)borate with Aryl Bromides
Sasa Duric,[a] Bernd M. Schmidt,[b] Nina M. Ninnemann,[a] Dieter Lentz,*[b] and
C. Christoph Tzschucke*[a]
Trifluorostyrene (TFS) derivatives have been widely used
as monomers for the preparation of polymers with fluorinat-
ed backbones.[1] However, they have seen little use in other
research fields, such as medicinal chemistry, probably due to
the lack of a convenient preparative method.[2] Most previ-
ous syntheses of TFS derivatives have involved multistep re-
action sequences, often involving unstable reagents or inter-
mediates and suffering from low overall yields.[1f,g,3] As a
more direct synthetic route, the palladium-catalyzed cross-
coupling of trifluorovinyl zinc reagents or trifluorovinyl tin
reagents with aryl iodides has been described.[1e,4] Recently,
a palladium-catalyzed reaction of tetrafluoroethylene (TFE)
with arylzinc compounds has been reported to give TFS de-
rivatives in moderate yields.[5] Although these catalytic
methods are more efficient than other multistep approaches,
their broad applicability suffers from the use of toxic and
unstable reagents, such as organostannanes, organozinc re-
agents, or gaseous and explosive tetrafluoroethylene. Orga-
noboron compounds have found widespread use in palladi-
um-catalyzed Suzuki–Miyaura coupling reactions because
they are easy to prepare, stable, and have relatively low tox-
icity.[6] In the context of TFS derivatives only two examples
for the coupling of potassium (trifluorovinyl)trifluoroborate
have been described so far.[7] Very recently, the copper-
mediated coupling of potassium (trifluoromethyl)trimethox-
yborate with aryl iodides has been reported.[8]
use of highly unstable TFE, toxic stannanes, or sensitive zinc
reagents (Scheme 1).
Scheme 1. Synthesis of trifluorovinylarenes by cross-coupling.
Lithium trimethoxy(1,2,2-trifluorovinyl)borate 1 can be
easily prepared in multigram quantities (25 g) by starting
from 1,1,1,2-tetrafluorethane (HFC-134a), which is a cheap
non-toxic bulk chemical commonly used as a refrigerant in
air conditioners. In a one-pot synthesis HFC-134a was treat-
ed with two equivalents of n-butyl lithium to give the corre-
sponding trifluorovinyl lithium in situ. Subsequent reaction
with trimethoxyborane gave 1 in good yield (Scheme 2).[9]
The product is an easy to handle white solid that is stable
under anhydrous conditions.
Scheme 2. Preparation of lithium trimethoxy(trifluorovinyl)borate 1 from
HFC-134a.
Herein, we report an efficient and convenient method for
the introduction of a trifluorovinyl group based on the palla-
dium-catalyzed Suzuki–Miyaura cross-coupling reaction.
This procedure employs stable borate 1 as the source of the
trifluorovinylgroup and, thus, circumvents the inconvenient
Crystals suitable for X-ray structure determination were
obtained by cooling a saturated solution of 1 in THF to 48C.
After one week, large colorless octahedral crystals of the
THF adduct were isolated under a cold stream of nitro-
gen.[10] As expected, a distorted tetrahedral arrangement of
the substituents around the boron atom is observed (Fig-
ure 1a).[8] The bond lengths within the trifluorovinyl group
[a] S. Duric, N. M. Ninnemann, Prof. Dr. C. C. Tzschucke
Institut fꢁr Chemie und Biochemie—Organische Chemie
Freie Universitꢂt Berlin, Takustr. 3, 14195 Berlin (Germany)
Fax : (+49)30-838-53357
closely resemble those in trifluoroethene.[11] Even the C F
À
E-mail: tzschucke@chemie.fu-berlin.de
bond to the a-fluorine atom (1.378 ꢀ) is only marginally
[b] B. M. Schmidt, Prof. Dr. D. Lentz
À
elongated compared with the C F bonds in fluorinated
Institut fꢁr Chemie und Biochemie—Anorganische Chemie
Freie Universitꢂt Berlin, Fabeckstr. 34–36, 14195 Berlin (Germany)
Fax : (+49)30-838-52424
ethenes. The lithium atom is coordinated in a distorted
trigonal-bipyramidal geometry to four oxygen atoms and the
a-fluorine atom of the trifluorovinyl group (Figure 1b). The
E-mail: lentz@chemie.fu-berlin.de
À
À
short Li F contact of 2.253 ꢀ is similar to the Li F separa-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103067.
tions found in comparable structures.[12] Together the lithium
Chem. Eur. J. 2012, 18, 437 – 441
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
437

Table 1. Optimization of the conditions for the cross-coupling reaction.[a]
Entry
Solvent
Base
T [8C]
Conversion [%][b]
1
2[c]
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
THF
THF
THF
THF
2-MeTHF
2-MeTHF
glyme
glyme
toluene
DMF
dioxane
ethyl acetate
THF
THF
THF
THF
THF
THF
THF
THF
THF
none
none
none
none
none
none
none
none
none
none
none
none
K3PO4
K3PO4
KF
60
60
80
90
60
80
60
80
60
60
80
80
60
90
60
90
60
60
60
60
60
19
4
38
44
15
20
20
12
0
0
27
18
100
70
85
78
93
51
93
76
27
KF
CsF
K2CO3
Cs2CO3
NaOMe
Et3N
[a] Reaction conditions: 2a (0.5 mmol),
1 (1.0 mmol), [Pd2ACHTUNGTRENNUNG(dba)3]
(0.5 mol%), XPhos (1.0 mol%), base (0.5 mmol), solvent (2 mL), 60–
1
908C, 15 h. [b] Based on the ratio of 3a to 2a, as determined by H NMR
spectroscopy. [c] LiCl (1.0 mmol) or tetra-n-butylammonium chloride
(TBACl) (1.0 mmol) as the additive.
increased the conversion (Table 1, entries 3 and 4), whereas,
in the presence of K3PO4 or KF, a higher reaction tempera-
ture led to slightly lower conversion (Table 1, entries 13, 14,
15, and 16).
Control experiments showed that borate 1 in THF is
stable at 608C, whereas heating to 908C causes disproportio-
nation of 1 into lithium dimethoxybis(1,2,2-trifluorovinyl)-
borate 1b and lithium tetramethoxyborate (Scheme 3).[16]
The role of the base in the coupling reaction remains un-
clear at present. Conceivably, the additives remove halide
Figure 1. ORTEP[14] diagrams containing ellipsoids drawn at the 50%
probability level. a) The molecular structure of the trimethoxy(1,2,2-tri-
fluorovinyl)borate ion. b) The distorted trigonal-bipyramidal coordina-
tion sphere of the lithium ion. A part of the coordination polymer is de-
picted in the Supporting Information.
and borate ions form a one-dimensional coordination poly-
mer.[13]
For the cross-coupling of borate 1 with aryl halides, we
chose para-bromoanisole 2a as the model substrate. After
ions or BACTHGNUTRENNU(G OMe)3, which is formed as a by-product and
which we found to inhibit the reaction.[17]
initial qualitative experiments, we decided to use [Pd2ACTHNUTRGNEN(UG dba)3]
(DBA=dibenzylideneacetone) and 2-dicyclohexylphosphi-
no-2’,4’,6’-triisopropylbiphenyl (XPhos) as the catalyst
system for the optimization of the reaction conditions.[15]
A
survey of aprotic solvents without added bases showed that
a variety of ethers were suitable for the reaction, with THF
being the most promising (Table 1, entries 1–8 and 11). In
contrast, no conversion was observed in toluene or DMF
(Table 1, entries 9 and 10). Different inorganic salts were
tested as basic additives, and indeed increased the conver-
sion of 2a, the best results being obtained with K3PO4
(Table 1, entry 13). CsF and Cs2CO3 were slightly less effec-
tive, whereas the amine base Et3N was essentially ineffective
(Table 1, entries 17, 19, and 21). We also examined the influ-
ence of reaction temperature with and without added base.
In the absence of base, increasing the reaction temperature
Scheme 3. Disproportionation of 1 at elevated temperature in THF.
We briefly investigated the influence of the halogen leav-
ing group on the cross-coupling reaction. With aryl iodides
the coupling product was formed, but consistently lower
conversions were observed than with the corresponding aryl
bromides (Table 2). Aryl chlorides, however, did not give
any detectable conversion. Interestingly, the conditions for
438
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ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 437 – 441

Synthesis of Trifluorostyrene Derivatives
COMMUNICATION
Table 2. Comparison of different aryl halides as electrophiles.[a]
Table 3. Comparison of different ligands.[a]
[mol%] Ligand[b]
E
T
Conversion
Entry
R
Yield [%][b]
Entry Pd source
[8C] [%][c]
X=Cl
X=Br
X=I
1
2
3
4
4-OMe
3-OMe
4-Me
0
–
0
–
100
76
85
55
61
72
36
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
N
2A
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
2A(dba)3]
(OAc)2]
(dppf)Cl2] 1.0
0.5
0.5
0.5
2.5
0.5
2.5
0.5
0.5
0.5
0.5
0.5
2.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
none
–
60
60
60
60
80
80
60
60
60
60
60
60
60
60
60
60
60
60
60
60
0
50
47
70
60
100
29
2
4
4
0
12
17
3
5
3
R
XPhos
XPhos
XPhos
XPhos
XPhos
MePhos
SPhos
JohnPhos 1.0
DavePhos 1.0
BrettPhos 1.0
RuPhos
PtBu3
PtBu2Me 1.0
PPh3
PCy3
1.0
2.0
5.0
1.0
5.0
1.0
1.0
CHTUNGTRENNUNG
2-Me
79
CHTUNGTRENNUNG
CHTUNGTRENNUNG
[a] Reaction conditions:
2
(0.5 mmol),
1
(1.0 mmol), [Pd2ACHTNGUTERNNU(G dba)3]
CHTUNGTRENNUNG
(0.5 mol%), XPhos (1.0 mol%), K3PO4 (0.5 mmol), THF (2 mL), 608C,
15 h. [b] Based on the ratio of 3 to 2, as determined by 1H NMR spectros-
copy.
CHTUNGTRENNUNG
CHTUNGTRENNUNG
N
R
R
the recently reported copper-mediated coupling of (trifluoro-
methyl)trimethoxyborate with aryl iodides were ineffective
for the coupling of trifluorovinylborate 1 with either bromo-
or iodoarenes.[8]
R
5.0
1.0
R
R
R
1.0
1.0
E
With bromomesitylene 2b, a more challenging substrate,
which gave only 50% conversion under our initially opti-
mized conditions, we tested several different phosphine li-
gands (selected examples are presented in Table 3). Among
these, only XPhos was found to be suitable, as even structur-
ally related Buchwald ligands[15] gave significantly lower
conversions. Eventually, we achieved complete conversion
of 2b by increasing the catalyst loading to 5 mol% palladi-
um and raising the temperature to 808C (Table 3, entry 6).
We successfully applied the reaction conditions to the syn-
thesis of different substituted trifluorvinylarenes 3 (Table 4).
By using catalyst loadings of 1 mol% Pd, different bromo-
benzenes with methyl or methoxy substituents could be cou-
pled. Likewise, 1- and 2-bromonaphthalene, as well as 9-bro-
mophenanthrene, proved to be good substrates for the reac-
tion.
R
XantPhos 1.0
1
0
16
0
T
IPrNHC
XPhos
none
2.0
1.0
–
G
AHCTUNGTRENNUNG
[a] Reaction conditions: 2b (0.5 mmol), 1 (1.0 mmol), catalyst, ligand,
K3PO4 (0.5 mmol), THF (2 mL), 60–808C, 15 h. [b] MePhos=2-dicyclo-
hexylphosphino-2’-methylbiphenyl,
2’,6’-dimethoxybiphenyl, JohnPhos=2-(di-tert-butylphosphino)biphenyl,
DavePhos=2-dicyclohexylphosphino-2’-(N,N-dimethylamino)biphenyl,
BrettPhos=2-(dicyclohexylphosphino)-3,6-dimethoxy-2’,4’,6’-triisopropyl-
1,1’-biphenyl,
phenyl, Cy=cyclohexyl, XantPhos=4,5-bis(diphenylphosphino)-9,9-di-
methylxanthene, IPrNHC=1,3-bis(2,6-diisopropylphenyl)imidazolium
SPhos=2-dicyclohexylphosphino-
RuPhos=2-dicyclohexylphosphino-2’,6’-diisopropoxybi-
chloride, DPPF=1,1’-bis(diphenylphosphino)ferrocene. [c] Based on the
ratio of 3b to 2b, as determined by H NMR spectroscopy.
1
In cases for which the standard conditions resulted in in-
complete conversion of the bromoarene, we adjusted the
temperature or catalyst loading to achieve complete conver-
sion. These adjustments were necessary to obtain pure prod-
ucts because mixtures of the starting bromoarene and the
corresponding trifluorovinylarene product are effectively in-
separable by chromatography. Thus, for ortho-substituted
arenes a reaction temperature of 808C was necessary to
reach complete conversion. Substrates with electron-with-
drawing substituents proved to be significantly less reactive
and required higher catalyst loadings of 5 mol% to com-
pletely convert the bromoarene. At first glance, this finding
is surprising, since aryl halides with electron-withdrawing
substituents are usually particularly good substrates for pal-
ladium-catalyzed cross-couplings, giving good yields and
high catalyst turn-over numbers.[18] This high reactivity has
been attributed to the fact that electron-poor aryl halides
undergo oxidative addition to palladium(0) complexes faster
than electron-rich aryl halides.[19] In a competition experi-
ment between para-bromoanisole 2a and para-bromobenzo-
nitrile 2i, we observed preferential reaction of the electron-
poor compound 2i in a 2.6:1 ratio, albeit in a low conversion
of 36%, which is comparable to the reaction of 2i alone
under these conditions (see Table 4). This result indicates
that, as expected, oxidative addition of bromobenzonitrile
2i to the palladium catalyst is faster than oxidative addition
of bromoanisole 2a. However, one of the subsequent steps,
transmetalation or reductive elimination of the product, is
less efficient for the palladium aryl intermediate with an
electron-deficient aryl group, and it is the efficiency of this
step that determines the yield of the catalytic process. A
similar correlation was recently observed for the palladium-
catalyzed direct arylation of pyridine N-oxides, for which
the coupling with electron-poor aryl halides was significantly
less effective than with electron-rich aryl halides.[20] Current-
ly, we are investigating the reactivity of isolated palladium
aryl complexes to elucidate the influence of the aryl sub-
stituent on the transmetalation.
In conclusion, the preparation of TFS derivatives by palla-
dium-catalyzed cross-coupling of trifluorovinylborate 1 and
aryl bromides is a straightforward and convenient method
that employs stable, easily handled starting materials and
avoids the use of toxic, dangerous, and unstable reagents.
Therefore, this method helps to make trifluorovinylarenes
Chem. Eur. J. 2012, 18, 437 – 441
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
439

C. C. Tzschucke et al.
Table 4. Synthesis of substituted trifluorostyrene derivatives 3. Isolated
yields based on 2.
Keywords: borates · cross-coupling · fluorine · palladium ·
trifluorovinyl compounds
[1] For reviews, see: a) R. Souzy, B. Ameduri, B. Boutevin, Prog.
Polym. Sci. 2004, 29, 75–106; b) R. Souzy, B. Ameduri, Prog.
Polym. Sci. 2005, 30, 644–687; c) R. Souzy, B. Ameduri, B. Boute-
vin, G. Gebel, P. Capron, Solid State Ionics 2005, 176, 2839–2848;
d) R. K. Nagarale, G. S. Gohil, V. K. Shahi, Adv. Colloid Interface
Sci. 2006, 119, 97–130; For selected examples see: e) M. P. C.
Conrad, M. S. Shoichet, Polymer 2007, 48, 5233–5240; f) R. B.
Hodgdon, J. Polym. Sci. Part A-1: Polym. Chem. 1968, 6, 171–191;
g) R. B. Hodgdon, D. I. Macdonald, J. Polym. Sci. Part A-1: Polym.
Chem. 1968, 6, 711–717.
[2] For leading reviews on fluoroorganic compounds in medicinal
chemistry, see: a) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur,
Chem. Soc. Rev. 2008, 37, 320–330; b) W. K. Hagmann, J. Med.
Chem. 2008, 51, 4359–4369; c) K. Mꢁller, C. Faeh, F. Diederich, Sci-
ence 2007, 317, 1881–1886.
3a; 97%
3b; 50%,[a] 99%[b,c]
3c; 76%,[a] 96%[d]
3d; 86%,[a] 99%[c]
3g; 79%,[a] 70%[c]
3e; 67%,[a] 99%[c]
3h; 78%,[a] 99%[b]
3 f; 75%,[a] 86%[d]
3i; 41%,[a] 96%[b]
[3] a) S. G. Cohen, H. T. Wolosinski, P. J. Scheuer, J. Am. Chem. Soc.
1949, 71, 3439–3440; b) M. Prober, J. Am. Chem. Soc. 1953, 75,
968–973; c) S. Dixon, J. Org. Chem. 1956, 21, 400–403; d) K. V.
Dvornikova, V. E. Platonov, G. G. Yakobson, J. Fluorine Chem.
1985, 28, 99–113; e) R. Anilkumar, D. J. Burton, Tetrahedron Lett.
2003, 44, 6661–6664; f) R. Anilkumar, D. J. Burton, J. Fluorine
Chem. 2005, 126, 1174–1184; g) S. Mizuta, N. Shibata, Y. Goto, T.
Furukawa, S. Nakamura, T. Toru, J. Am. Chem. Soc. 2007, 129,
6394–6395.
3j; 99%[b]
3k; 99%[b]
3l; 99%[b,c]
[4] For coupling of trifluorvinyl zinc reagents, see: a) J.-P. Gillet, R.
Sauvetre, J.-F. Normant, Tetrahedron Lett. 1985, 26, 3999–4002;
b) P. L. Heinze, D. J. Burton, J. Fluorine Chem. 1986, 31, 115–119;
c) F. Tellier, R. SauvÞtre, J. F. Normant, Y. Dromzee, Y. Jeannin, J.
Organomet. Chem. 1987, 331, 281–298; d) P. L. Heinze, D. J. Burton,
J. Org. Chem. 1988, 53, 2714–2720; e) R. Anilkumar, D. J. Burton,
Tetrahedron Lett. 2002, 43, 2731–2733; f) A. Raghavanpillai, D. J.
Burton, J. Org. Chem. 2004, 69, 7083–7091; g) M. Roemer, D.
Lentz, Chem. Commun. 2011, 47, 7239–7241. Coupling of trifluor-
vinyl tin reagents: h) I. P. Beletskaya, J. Organomet. Chem. 1983,
250, 551–564; i) F. A. Akkerman, R. Kickbusch, D. Lentz, Chem.
Asian J. 2008, 3, 719–731; j) M. Roemer, D. Lentz, Eur. J. Inorg.
Chem. 2008, 4875–4878; k) T. Lechel, J. Dash, P. Hommes, D.
Lentz, H.-U. Reissig, J. Org. Chem. 2010, 75, 726–732; l) M.
Roemer, P. Schmiel, D. Lentz, Organometallics 2011, 30, 2063–2066.
[5] M. Ohashi, T. Kambara, T. Hatanaka, H. Saijo, R. Doi, S. Ogoshi, J.
Am. Chem. Soc. 2011, 133, 3256–3259.
3m; 99%
[a] Yields (in italics) based on the ratio of 3 to 2, as determined by
1H NMR spectroscopy. [b] [Pd
2A(dba)3] (2.5 mol%), XPhos (5.0 mol%).
[c] Reaction temperature 808C instead of 608C. [d] By using (XPhos)–
palladium(II)–phenethylamine chloride (1.0 mol%) as the precatalyst
(see the Supporting Information for the structure of this compound).
3n; 97%
3o; 99%
CTHUNGTRENNUNG
more readily available for investigations of potential appli-
cations in other fields of chemistry, such as materials science
or medicinal chemistry.
[6] For selected reviews, see: a) N. Miyaura, A. Suzuki, Chem. Rev.
1995, 95, 2457–2483; b) A. Suzuki, J. Organomet. Chem. 1999, 576,
147; c) A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114, 4350–4386;
Angew. Chem. Int. Ed. 2002, 41, 4176–4211; d) F. Bellina, A. Carpi-
ta, R. Rossi, Synthesis 2004, 2419–2440; e) K. C. Nicolaou, P. G.
Bulger, D. Sarlah, Angew. Chem. 2005, 117, 4516–4563; Angew.
Chem. Int. Ed. 2005, 44, 4442–4489; f) G. A. Molander, B. Canturk,
Angew. Chem. 2009, 121, 9404–9425; Angew. Chem. Int. Ed. 2009,
48, 9240–9261; g) A. Suzuki, Angew. Chem. 2011, 123, 6854–6869;
Angew. Chem. Int. Ed. 2011, 50, 6722–6737.
Experimental Section
General procedure for the palladium-catalyzed trifluorovinylation: In a
closed vial, under argon, K3PO4 (106 mg, 0.5 mmol),
1.0 mmol), [Pd2A(dba)3] (2.3 mg, 0.0025 mmol), XPhos (2.4 mg,
0.005 mmol), and arylhalide 2 (0.5 mmol) in THF (2 mL) were stirred for
15 h at 608C. The reaction mixture was diluted with pentane and filtered
through a short plug of silica gel. Evaporation of the solvent under re-
duced pressure gave the product.
1 (192 mg,
CHTUNGTRENNUNG
[7] a) H.-J. Frohn, N. Y. Adonin, V. V. Bardin, V. F. Starichenko, J. Fluo-
rine Chem. 2002, 117, 115–120; b) H. J. Frohn, N. Y. Adonin, V. V.
Bardin, V. F. Starichenko, Tetrahedron Lett. 2002, 43, 8111–8114.
[8] T. Knauber, F. Arikan, G.-V. Rçschenthaler, L. J. Gooßen, Chem.
Eur. J. 2011, 17, 2689–2697.
[9] H. J. Frohn, V. V. Bardin, Z. Anorg. Allg. Chem. 2001, 627, 2499–
2505.
[10] The solvate of 1 is rather unstable, the crystals lose solvent at room
temperature and the unsolvated compound remains as a colorless
powder.
Acknowledgements
We are grateful to the Deutsche Forschungsgemeinschaft for support
through the graduate school “Fluorine as Key Element” GK 1582/1
(B.M.S., D.L.) and to the Center of Supramolecular Interactions, Freie
Universitꢂt Berlin for funding (S.D., N.M.N., C.C.T.). We thank Solvay
Chemicals for a gift of HFC-134a. Part of this work was conducted
within a project in the Excellence Cluster “Unifying Concepts in Cataly-
sis”, Berlin.
[11] D. Lentz, A. Bach, J. Buschmann, P. Luger, M. Messerschmidt,
Chem. Eur. J. 2004, 10, 5059–5066.
440
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ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Synthesis of Trifluorostyrene Derivatives
COMMUNICATION
[12] a) D. Stalke, K. H. Whitmire, J. Chem. Soc. Chem. Commun. 1990,
833–834; b) H. Plenio, Chem. Rev. 1997, 97, 3363–3384.
sponding boronic acid. See: a) M. Butters, J. N. Harvey, J. Jover,
A. J. J. Lennox, G. C. Lloyd-Jones, P. M. Murray, Angew. Chem.
2010, 122, 5282–5286; Angew. Chem. Int. Ed. 2010, 49, 5156–5160.
In aqueous media, the transmetalation reaction proceeds faster
through the boronic acid than through the respective aryltrihydroxy-
borate. See: b) B. P. Carrow, J. F. Hartwig, J. Am. Chem. Soc. 2011,
133, 2116–2119; c) C. Amatore, A. Jutand, G. Le Duc, Chem. Eur. J.
2011, 17, 2492–2503. We therefore considered that the basic addi-
tive might serve as a source of water. However, reactions for which
we deliberately added different amounts of water led to diminished
yields.
[13] We did not investigate the degree of aggregation of 1 in THF. How-
7
ever, the observed Li NMR signal at d=À0.65 ppm, compared with
d=À0.58 ppm for LiBF4, suggests a solvent-separated ion pair. See:
H. J. Reich, J. P. Borst, R. R. Dykstra, D. P. Green, J. Am. Chem.
Soc. 1993, 115, 8728–8741.
[14] ORTEP3 for Windows: L. J. Farrugia, J. Appl. Crystallogr. 1997, 30,
565–565; CCDC-846336 (1) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[15] For a review, see: a) R. Martin, S. L. Buchwald, Acc. Chem. Res.
2008, 41, 1461–1473; for selected recent examples of Suzuki–
Miyaura cross-couplings with dialkylbiaryl phosphine ligands, see:
b) K. L. Billingsley, K. W. Anderson, S. L. Buchwald, Angew. Chem.
2006, 118, 3564–3568; Angew. Chem. Int. Ed. 2006, 45, 3484–3488;
c) K. Billingsley, S. L. Buchwald, J. Am. Chem. Soc. 2007, 129,
3358–3366; d) B. Bhayana, B. P. Fors, S. L. Buchwald, Org. Lett.
2009, 11, 3954–3957; e) T. Kinzel, Y. Zhang, S. L. Buchwald, J. Am.
Chem. Soc. 2010, 132, 14073–14075.
[18] a) N. Miyaura, A. Suzuki, J. Chem. Soc. Chem. Commun. 1979, 866–
867; b) N. Miyaura, T. Yanagi, A. Suzuki, Synth. Commun. 1981, 11,
513–519.
[19] a) P. Fitton, E. A. Rick, J. Organomet. Chem. 1971, 28, 287–291;
b) J.-F. Fauvarque, F. Pflꢁger, M. Troupel, J. Organomet. Chem.
1981, 208, 419–427; c) C. Amatore, F. Pflꢁger, Organometallics
1990, 9, 2276–2282.
[20] a) L.-C. Campeau, D. R. Stuart, J.-P. Leclerc, M. Bertrand-Laperle,
E. Villemure, H.-Y. Sun, S. Lasserre, N. Guimond, M. Lecavallier,
K. Fagnou, J. Am. Chem. Soc. 2009, 131, 3291–3306; b) H.-Y. Sun,
S. I. Gorelsky, D. R. Stuart, L.-C. Campeau, K. Fagnou, J. Org.
Chem. 2010, 75, 8180–8189; c) S. Duric, C. C. Tzschucke, Org. Lett.
2011, 13, 2310–2313.
[16] N. Y. Adonin, V. V. Bardin, H.-J. Frohn, Organometallics 2004, 23,
535–539.
[17] The coupling of meta-bromoanisole 2c proceeded only in 59% con-
version in the presence of B
conversion without B(OMe)3. It has been shown that aryltrifluoro-
borates undergo transmetalation only after hydrolysis to the corre-
N
Received: September 30, 2011
Revised: November 10, 2011
Published online: December 12, 2011
A
Chem. Eur. J. 2012, 18, 437 – 441
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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