A general method to fluorous ponytail-substituted aromatics

Article abstract of DOI:10.1016/S0040-4039(01)00714-6

Palladium-catalyzed olefination of aryl halides led to a variety of fluorous ponytail-substituted, functionalized aryl compounds with good to excellent yields. The same chemistry was also applied to the synthesis of binaphathols bearing fluorinated ponytails.

Full text of DOI:10.1016/S0040-4039(01)00714-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4275–4278
A general method to fluorous ponytail-substituted aromatics
Weiping Chen, Lijin Xu and Jianliang Xiao*
Leverhulme Centre for Innovative Catalysis, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
Received 19 March 2001; revised 19 April 2001; accepted 27 April 2001
Abstract—Palladium-catalyzed olefination of aryl halides led to a variety of fluorous ponytail-substituted, functionalized aryl
compounds with good to excellent yields. The same chemistry was also applied to the synthesis of binaphathols bearing
fluorinated ponytails. © 2001 Elsevier Science Ltd. All rights reserved.
Aryl compounds bearing long fluoroalkyl chains have
been used in a number of instances as building blocks
for the construction of soluble ligands applicable to
catalysis in supercritical CO2 (scCO2) and fluorous
phases.1–6 However, only a few approaches have been
developed for the preparation of fluoroalkylated aro-
matics.7–15 The most frequently used method is based
We recently developed two simple, efficient routes to
fluoroalkylated arylphosphines.16,17 The key step of one
method is the copper-mediated coupling of bro-
moarylphosphine oxides with perfluoroalkyl iodides.
The other method involves the Heck reaction of the
same oxides with 1H,1H,2H-perfluoro-1-alkenes. With
these two methods, arylphosphines with fluorous pony-
tails with or without ethylene spacers can easily and
economically be accessed. In continuing our study in
this area, we present herein a simple, general method
for the synthesis of various aromatics bearing ethylene-
spaced perfluoroalkyl chains. The method simply
involves the Heck coupling of aryl halides with com-
mercially available fluoroalkyl-substituted ethylenes fol-
lowed by the reduction of the resultant double bonds
(Scheme 1). While the preparation of b-trifluoromethyl-
styrene via the palladium-catalyzed arylation of trifl-
uoropropene was reported two decades ago, we are not
aware of any reports that have extended the chemistry
to terminal olefins with long fluoroalkyl chains.18,19
on the copper-mediated cross coupling of
a
perfluoroalkyl iodide with an aryl halide to give a
perfluoroalkylated aromatic species.7,9,10,13 This method
does not allow one to introduce an ethylene spacer
between the aromatic ring and the perfluoroalkyl unit,
and this spacer is often necessary to reduce the strong
electron-withdrawing effect of the latter. Spacer groups
can be introduced by the copper-catalyzed coupling of
arylmetal reagents, such as arylmagnesium bromides,
with 1H,1H,2H,2H-perfluoroalkyl iodides, which leads
to aromatics having ethylene-spaced perfluoroalkyls.8,11
In this case, however, the purification procedure is
tedious because of the formation of fluorous by-prod-
ucts, such as the homo-coupling product of
1H,1H,2H,2H-perfluoroalkyl iodides, which is difficult
to remove. In addition, functional groups, such as CN,
CꢀO, CO2R, NH2 and OH, which are sensitive to
organometallic reagents, are not tolerated.
The olefination of aryl halides proceeded smoothly to
give the expected trans product. In a typical reaction,
an aryl halide was mixed with 1.1 equiv. of a
H2
Pd/C or
Rh/C
Pd catalyst
Rf
Rf
Ar-X
Ar
+
Ar
Rf
EtOAc
r.t.
NaOAc
DMF
110 - 140 oC
Scheme 1.
Keywords: fluorinated aromatics; Heck reaction; fluorous ponytails; palladium catalysts.
* Corresponding author. Tel.: 44-(0)151-7942937; fax: 44-(0)151-7943589; e-mail: j.xiao@liv.ac.uk
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00714-6

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W. Chen et al. / Tetrahedron Letters 42 (2001) 4275–4278
fluoroolefin, ca. 1.3 equiv. of NaOAc, and 0.5–1 mol%
of the Herrmann–Beller palladacycle catalyst in DMF
and, after heating for a certain time, the trans olefin
was obtained in more than 90% isolated yields in most
cases without optimization (Table 1).20,21 As with nor-
mal Heck reactions, a variety of functionalities are
tolerated, making further functionalization of the prod-
ucts feasible. The coupling reaction works equally well
with both long and short fluoroolefins and so aromatics
with fluorous ponytails of different sizes can easily be
obtained. Thus, the olefination of 4-bromobezaldehyde
bromoiodobenzenes with 1H,1H,2H-perfluoro-1-octene
each selectively gave the mono-substituted bromides in
high yields (entries 13–15).
To use these ponytail-attached aromatics as building
blocks for ligands, the CꢀC double bonds would nor-
mally need to be reduced. Hydrogenation of the double
bonds by Pd/C did not proceed with the crude Heck
reaction products, probably due to poisoning of the
catalyst by the phosphine ligand in the mixture. Consis-
tent with this, purification of the perfluoroalkenyl-sub-
stituted aromatics by flash chromatography allowed
easy reduction of the CꢀC double bonds under stan-
dard Pd/C catalyzed hydrogenation conditions. How-
ever, reduction of the perfluoroalkenyl-substituted aryl
bromides was accompanied with debromination under
the hydrogenation conditions. Fortunately, on replace-
ment of Pd/C with Rh/C, the olefinic double bonds of
the bromides were selectively reduced to give
1H,1H,2H,2H-perfluoroalkyl-substituted aryl bro-
mides. Similar observations were also made in Ref. 19
with
1H,1H,2H-perfluoro-1-hexene,
1H,1H,2H-
perfluoro-1-octene, and 1H,1H,2H-perfluoro-1-decene
all proceeded to give the corresponding trans olefins in
over 90% yields (Table 1, entries 1–3). A longer reac-
tion time was employed for 1H,1H,2H-perfluoro-1-hex-
ene, considering its higher volatility. Aryl bromides and
iodides can both be used as substrates. In the case of
the latter, however, the presence of phospine ligands
inhibits the coupling reactions, as is known for other
Heck reactions involving iodides.22 Thus, while the
reaction of methyl 4-bromobenzoate with 1H,1H,2H-
perfluoro-1-octene, when catalyzed by the Herrmann–
Beller catalyst, afforded trans methyl 4-(1H,2H-
perfluoro-1-octenyl)benzoate in 97% yield at 125°C in
10 h reaction time, the reaction with the corresponding
iodide yielded the benzoate in less than 20% yield when
performed at 100°C for 16 h (entries 5, 6). The coupling
reaction involving the iodide is better performed under
the Jeffery conditions, that is, in a polar solvent such as
DMF in the presence of a quaternary ammonium salt
as promoter without using a phosphine.23 Under such
conditions, high yields of the coupling product were
obtained with methyl 4-iodobenzoate as well as 4-
iodoacetanilide (entries 7, 8). With the deactivated 4-
bromotoluene and 4-bromoanisole, higher temperatures
and longer reaction time were necessary, as is true of
Heck reactions involving other olefins (entries 11, 12).22
Because of the difference in reactivity between aryl
bromides and iodides, the Heck reaction of the three
Using the protocol developed, 3- or 4-(1H,1H,2H,2H-
perfluorooctyl)bromobenzene, one of the key building
blocks for scCO2 and fluorous-soluble phosphines, can
now be accessed more conveniently and in a far higher
yield. Thus, following hydrogenation by Rh/C of the
coupling
product
4-(1H,2H-perfluorooctenyl)-
bromobenzene, the saturated compound was obtained
in 92% yield, corresponding to an overall isolated yield
of 84%. With the previously reported Grignard route,
starting with dibromobenzene, these compounds were
produced in yields less than 50%, and isolation of the
pure compound from the crude product, which contains
a dimerized fluoroalkyl iodide, proved to be labori-
ous.11
We also applied the same chemistry to the fluoroalkyla-
tion of a BINOL derivative. The reactivity of the benzyl
protected 6,6%-dibromo-1,1%-bi-2-naphthol appears to be
Table 1. Preparation of fluoroponytail-attached aromatics by arylation of CH2ꢀCHRf with ArX
Entry
Ar
X
Rf
Catal.a
Temp. (°C)/Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
4-HOC-C6H4
4-HOC-C6H4
4-HOC-C6H4
4-Ac-C6H4
4-MeOCO-C6H4
4-MeOCO-C6H4
4-MeOCO-C6H4
4-AcHN-C6H4
4-NC-C6H4
4-F-C6H4
4-Me-C6H4
4-MeO-C6H4
2-Br-C6H4
3-Br-C6H4
Br
Br
Br
Br
Br
I
n-C4F9
A
A
A
A
A
A
B
125/12
125/5
125/8
93
94
94
96
97
B20
93
95
93
n-C6F13
n-C8F17
n-C6F13
n-C6F13
n-C6F13
n-C6F13
n-C6F13
n-C6F13
n-C6F13
n-C6F13
n-C6F13
n-C6F13
n-C6F13
n-C6F13
125/6
125/10
100/16
110/24
120/24
125/10
140/72
140/72
140/72
110/24
110/24
110/24
I
I
B
9
Br
Br
Br
Br
I
A
A
A
A
B
10
11
12
13
14
15
87
75c
70c
86
I
I
B
B
82
91
4-Br-C6H4
a Catalyst, A=Herrmann–Beller palladacycle catalyst; B=Pd(OAc)2+n-Bu4NBr (20 mol%).
b Isolated yield.
c Determined by 1H NMR.

W. Chen et al. / Tetrahedron Letters 42 (2001) 4275–4278
4277
Br
Br
Rf
1)
Rf
Palladacycle
OBn
OBn
OH
OH
2) H2
Pd/C
Rf
Rf = C6F13, 86% overall yield.
Rf = C8F17, 82% overall yield.
Scheme 2.
similar to activated aryl bromides, such as 4-
acetylphenyl bromide and 4-bromobenzaldehyde. Thus,
the coupling of the benzyl protected (R)-6,6%-dibromo-
1,1%-bi-2-naphthol with 1H,1H,2H-perfluoro-1-octene
was complete in 24 h reaction time at 125°C to give the
expected trans substituted product in 95% isolated
yield.20 Following hydrogenation by Pd/C to reduce the
double bonds and debenzylate at the same time, the
fluoroalkylated (R)-1,1%-bi-2-naphthol was obtained in
86% overall yield (Scheme 2).21 The coupling with
1H,1H,2H-perfluoro-1-decene worked equally well,
affording the substituted binaphthol in 82% overall
yield. Binaphthols are extensively used as ligands or
building blocks for ligands in asymmetric catalysis. Our
methodology offers an easy and versatile route for
adapting such ligands for catalysis in scCO2 or
perfluorocarbons. A multi-fluoroalkylated BINOL has
recently been prepared via the organolithium mediated
reaction of a 6,6%-dibromo-1,1%-bi-2-naphthol derivative
with a fluoroalkylated bromosilane.15
6. De Wolf, E.; Van Koten, G.; Deelman, B. J. Chem. Soc.
Rev. 1999, 28, 37.
7. Bhattacharyya, P.; Gudmunsen, D.; Hope, E. G.; Kem-
mitt, R. D. W.; Paige, D. R.; Stuart, A. M. J. Chem.
Soc., Perkin Trans. 1 1997, 3609.
8. Kainz, S.; Koch, D.; Baumann, W.; Leitner, W. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1628.
9. Betzemeier, B.; Knochel, P. Angew. Chem., Int. Ed. Engl.
1997, 36, 2623.
10. Pozzi, G.; Montanari, F.; Quici, S. Chem. Commun. 1997,
69.
11. Kainz, S.; Luo, Z.; Curran, D. P.; Leitner, W. Synthesis
1998, 1425.
12. Sinou, D.; Pozzi, G.; Hope, E. G.; Stuart, A. M. Tetra-
hedron Lett. 1999, 40, 849.
13. Mathivet, T.; Monflier, E.; Castanet, Y.; Mortreux, A.;
Couturier, J.-L. Tetrahedron Lett. 1999, 40, 3885.
14. Richter, B.; Deelman, B.-J.; Van Koten, G. J. Mol. Catal.
1999, 145, 317.
15. Nakamura, Y.; Takeuchi, S.; Ohgo, Y.; Curran, D. P.
Tetrahedron Lett. 2000, 41, 57.
In conclusion, the results presented here demonstrate
that fluorous ponytail-substituted aromatics are readily
accessible by the Heck reaction. The approach over-
comes problems encountered with currently used meth-
ods, allows easy access to fluorous and scCO2-soluble
ligands, and should encourage the wider use of these
novel solvents in catalysis.
16. Chen, W.; Xiao, J. Tetrahedron Lett. 2000, 41, 3697.
17. Chen, W.; Xu, L.; Xiao, J. Org. Lett. 2000, 2, 2675.
18. Fuchikami, T.; Yatabe, M.; Ojima, I. Synthesis 1981, 365.
19. While this manuscript was in preparation, a paper
appeared on the Heck reaction of perfluoroalkenes with
arenediazonium salts: Darses, S.; Pucheault, M.; Geneˆt,
J.-P. Eur. J. Org. Chem. 2001, 1121.
20. A typical procedure is given for (R)-6,6%-bis(1H,2H-
perfluoro-1-octenyl)-2,2%-dibenzyloxy-1,1%-binaphthyl:
A
Acknowledgements
solution of (R)-6,6%-dibromo-2,2%-dibenzyloxy-1,1%-binaph-
thyl (1.24 g, 2 mmol), 1H,1H,2H-perfluoro-1-octene (1.73
g, 5 mmol), Hermman’s palladacycle catalyst (19 mg, 0.02
mmol) and NaOAc (410 mg, 5 mmol) in DMF (10 ml)
was stirred for 24 h at 125°C. After cooling to ambient
temperature, the solvent was removed under reduced
pressure, and the residue was partitioned between EtOAc
(50 ml) and water (50 ml). The organic layer was sepa-
rated, washed with water (50 ml) and brine (50 ml), dried
(MgSO4), and evaporated under reduced pressure. The
residue was purified by flash chromatography (SiO2, hex-
ane:EtOAc=8:1) to give the title compound as pale-
We are grateful to the EPSRC, the Leverhulme Centre
for Innovative Catalysis and its Industrial Partners
(Synetix, Johnson Matthey, Catalytica, Air Products,
and Syntroleum) for financial support.
References
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yellow oil (2.19 g, 95%). H NMR (CDCl3): l 7.96 (2H,
d, J=9.06 Hz), 7.92 (2H, s), 7.45 (2H, d, J=9.06), 7.36
(2H, dd, J=8.80 and 1.64 Hz), 6.96ꢀ7.18 (14H, m), 6.19
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W. Chen et al. / Tetrahedron Letters 42 (2001) 4275–4278
21. A typical procedure for reduction is given for (R)-6,6%-
bis(1H,1H,2H,2H-perfluoro-1-octyl)-2,2%-dihydroxy-1,1%-
binaphthyl: A mixture of (R)-6,6%-bis(1H,2H-perfluoro-1-
octenyl)-2,2%-dibenzyloxy-1,1%-binaphthyl (1.73 g, 1.5
mmol), 10% Pd/C (400 mg) and EtOAc (10 ml) was
stirred overnight at room temperature under 30 bar of
hydrogen. After carefully releasing the hydrogen, the
mixture was filtered through a pad of Celite. The filtrate
was evaporated under reduced pressure. The resulting
residue was purified by flash chromatography (SiO2, hex-
ane:EtOAc=2:1) to give the title compound as pale-yel-
low oil, which crystallized on standing (1.34 g, 91%). H
1
NMR (CDCl3): l 7.94 (2H, d, J=8.80 Hz), 7.73 (2H, s),
7.39 (2H, d, J=8.80 Hz), 7.17 (2H, dd, J=8.52 and 1.92
Hz), 7.10 (2H, d, J=8.52 Hz), 5.01 (2H, s), 3.04 (4H, m),
2.43 (4H, m). Anal. calcd for C36H20F26O2: C, 44.19; H,
2.06. Found: C, 44.58; 1.85; [h]1D0 −33.33 (c 1.1, CHCl3).
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