Novel and efficient synthesis of perfluoroalkylated arylphosphines

Article abstract of DOI:10.1016/S0040-4039(00)00445-7

A novel, high-yield route has been developed for the synthesis of perfluoroalkylated arylphosphines, involving simple, copper-mediated coupling of haloarylphosphine oxides with perfluoroalkyl iodides followed by reduction with trichlorosilane. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00445-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3697–3700
Novel and efficient synthesis of perfluoroalkylated
arylphosphines
∗
Weiping Chen and Jianliang Xiao
Leverhulme Centre for Innovative Catalysis, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
Received 15 February 2000; accepted 13 March 2000
Abstract
A novel, high-yield route has been developed for the synthesis of perfluoroalkylated arylphosphines, involving
simple, copper-mediated coupling of haloarylphosphine oxides with perfluoroalkyl iodides followed by reduction
with trichlorosilane. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: perfluoroalkylated phosphines; copper-mediated coupling; arylphosphines.
One of the current frontiers in homogeneous catalysis involves the exploration of non-traditional reac-
1
tion media such as water, ionic liquids, supercritical carbon dioxide (scCO ) and perfluorocarbons. For
2
catalysis in some of these solvents, modifications to ligands have to be made in order to make their metal
complexes soluble. A well-established strategy for catalysis by organometallic complexes in scCO and
2
a fluorous phase is to modify known ligands with fluorinated groups such as perfluoroalkyls, which are
2,3
known to exhibit exceptionally high solubility in these solvents. Arylphosphines are perhaps the most
1
widely used ligands in homogeneous catalysis. Accordingly, synthetic routes have been developed for
the attachment of fluorinated ponytails to these phosphines.4 PPh3 [4-C H (CH ) R ] (n=1–3, m=0,
–7
−n
6
4
2 m f n
2
, R =perfluoroalkyl) have been prepared by bromine–lithium exchange processes between fluoroalkyl-
f
4–6
substituted bromobenzenes and nBuLi at −78°C followed by metathesis with PPh3 Cln. The disad-
−n
vantages of the previous methods include that, for each fluorophosphine, the synthesis has to start with
the preparation of fluoroalkylated aromatics using fluoroalkyl iodides followed by the metathesis, relies
on the use of moisture-sensitive and pyrophoric organolithium reagents at low temperature and ends at
relatively inefficient utilisation of the iodides, often the most expensive of all reagents involved. Herein,
we describe a convenient and high-yield route to arylphosphines bearing perfluorinated ponytails based
on the direct coupling of fluoroalkyl iodides with haloarylphosphine oxides.
Cross-coupling of fluoroalkyl iodides with iodoaromatic compounds to give fluoroalkyl-substituted
aromatics in the presence of copper was reported by McLoughlin and Thrower more than three decades
8
9,10
ago. The reaction was later extended to include bromoaromatics.
Functional groups such as OH,
∗
Corresponding author. Tel: +44-(0)151-7942979; fax: +44-(0)151-7943589; e-mail: j.xiao@liv.ac.uk (J. Xiao)
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00445-7
tetl 16725

3
698
CO R and NH in the starting aromatics are tolerated. Prompted by these early findings, we attempted
2
2
the coupling of haloarylphosphine oxides with perfluoroalkyl iodides. Since these phosphine oxides
are easily available starting from 1,4-dibromobenzene and phosphorus chlorides using established
1
1
procedures, such a reaction would offer a much simplified route to fluoroalkylated phosphines,
involving just two steps, coupling and subsequent reduction (Scheme 1). To our delight, coupling of
OPPh (4-C H Br) (n=1–3) with IC F proceeded smoothly in the presence of copper powder to
n−3
6
4
n
6 13
give the perfluorohexyl-substituted phosphine oxides OPPh (4-C H C F ) in greater than 90%
n−3
6
4 6 13 n
1
2
isolated yields (Table 1). In all the cases including the coupling with IC F , the prefluoroalkylated
8
17
phosphine oxides were obtained as crystalline solids. The obtained yields are remarkable as most
previously reported coupling reactions of aryl iodides and bromides have yields lower than 70%.8
The key to the success of our method is the use of oxidised phosphines. When bromoarylphosphines
were employed instead of the oxides, complex mixtures were obtained under otherwise identical reaction
–10
0
conditions. The presence of a catalytic amount of 2,2 -bipyridine (bipy) in the reaction lowers the reaction
temperature without affecting the conversion and yield. Bipy may play a role in facilitating metallation
8
of copper by IC F . The phosphine oxide may play a similar role, thus promoting higher yields
6
13
under milder conditions. As with the coupling reactions of other haloaromatics, DMSO is the solvent
8
–10
of choice.
In DMF, the reaction was sluggish and less clean. The chloride analogues OPPh (4-
n−3
C H Cl) failed to react. A longer reaction time was required on going from OPPh (C H Br) to OP(4-
6
4
n
2
6
4
C H Br) due to increasing substitution by the perfluorohexyl moiety and accompanied decrease in
6
4
3
solubility of the substituted oxides in the solvent. Solubility also appears to be responsible for the
slightly lower yield obtained with OP(4-C H C F ) . When the reaction was carried out in a perfluoro-
6
4 6 13 3
1
9
,3-dimethylcyclohexane and DMSO (5:1, vol.) mixture, the yield of OP(4-C H C F ) increased to
6 4 6 13 3
5%. Solubility was even more of a problem with the longer IC F . Thus, when the reaction of OP(4-
8
17
C H Br) with IC F was performed in DMSO, a yield of only 45% was obtained. Remarkably, when
6
4
3
8 17
performed in the perfluoro-1,3-dimethylcyclohexane and DMSO mixture, the reaction proceeded to give
the substituted product in 93% isolated yield. While the coupling reactions above were performed under
nitrogen, they can also be carried out in air without notable effects on yields.
Scheme 1. Synthesis of fluoroalkylated phosphines by Cu-mediated cross-coupling followed by reduction with silane. General
conditions for cross-coupling: 1.0–1.1 equiv. IR
f
and 2–3 equiv. copper powder (relative to bromine), 20 mol% bipy, 110–120°C,
, 5–15 equiv. NEt , reflux, 6 h
15–72 h. General conditions for reduction: 5–15 equiv. HSiCl
3
3
The phosphines were released from the oxides by reduction with trichlorosilane.13 The reaction was
carried out by simply heating a mixture of a perfluoroalkylated phosphine oxide, trichlorosilane and
triethylamine in toluene at 120°C for a few hours, affording the free phosphines in almost quantitative
1
4
isolated yields (Table 2). Thus, about 90% of the perfluoroalkyl reagents were effectively incorporated
into the desired product. In contrast, previous methodologies led to much less efficient use of the
4
–6
expensive perfluoroalkyl iodides.
In conclusion, we have developed a novel, convenient, and economical route for the synthesis of
perfluoroalkylated arylphosphines useful for catalysis in scCO and a fluorous phase. The key step
2
of the route, requiring no special techniques to handle, comprises of the copper-mediated coupling of
a haloarylphosphine oxide with a perfluoroalkyl iodide. The reaction could easily be scaled up and
extended to other fluoroalkyl iodides.

3
699
Table 1
6 4 n f
Copper-mediated cross-coupling of OPPhn−3(4-C H Br)
with IR a
Table 2
6 4 f n
Reduction of fluorophosphine oxides OPPhn−3(4-C H R )
by trichlorosilanea
Acknowledgements
We thank the EPSRC for a postdoctoral research fellowship (W.C.) and the industrial partners (ICI,
Johnson Matthey, Catalytica, Eastman Chemicals, Air Products) of the Leverhulme Centre for Innovative
Catalysis for support. We are also grateful to Professor Eric Hope for providing us with some samples of
the fluorophosphines.
References
1
. Applied Homogeneous Catalysis with Organometallic Compounds; Cornils, B.; Herrmann, W. A., Eds.; VCH: Weinheim,
996.
1
2
3
4
. Jessop, P. G.; Ikariya, T.; Noyori, R. Chem. Rev. 1999, 99, 475.
. Horváth, I. T.; Rábai, J. Science 1994, 266, 72.
. Bhattacharyya, P.; Gudmunsen, D.; Hope, E. G.; Kemmitt, R. D. W.; Paige, D. R.; Stuart, A. M. J. Chem. Soc., Perkin
Trans. 1 1997, 3609.
5. Kainz, S.; Koch, D.; Baumann, W.; Leitner, W. Angew. Chem., Int. Ed. Engl. 1997, 36, 1628.

3
700
6
7
8
9
. Betzemeier, B.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1997, 36, 2623.
. Carroll, M. A.; Holmes, A. B. Chem. Commun. 1998, 1395.
. McLoughlin, V. C. R.; Thrower, J. Tetrahedron 1969, 25, 5921.
. Chen, G. J.; Tamborski, C. J. Fluorine Chem. 1989, 43, 207.
10. Chen, G. J.; Chen, L. S.; Eapen, K. C. J. Fluorine Chem. 1993, 65, 59.
1
1
1. Benassi, R.; Schenetti, M. L.; Taddei, F.; Vivarelli, P.; Dembech, P. J. Chem. Soc., Perkin Trans. 2 1974, 1338.
2. A typical preparation is given for tris(4-tridecafluorohexylphenyl)phosphine oxide. A mixture of tris(4-bromophenyl)-
phosphine oxide (515 mg, 1.0 mmol), 1-iodoperfluorohexane (1.405 g, 3.2 mmol), copper powder (450 mg, 7.1 mmol),
0
2
,2 -bipyridine (34 mg, 0.2 mmol) and DMSO (20 ml) was stirred at 120°C for 36 h. After cooling to room temperature,
the reaction mixture was diluted with CHCl
CHCl
(2×20 ml). The organic layer was separated, washed with 1N HCl (2×50 ml), water (2×50 ml) and brine (50 ml),
dried (MgSO ) and evaporated under reduced pressure to give the crude product, which upon recrystallisation from EtOH
3
(50 ml) and water (50 ml), filtered through a pad of Celite and washed with
3
4
yielded the desired compound as colourless needles (1.123 g, 91%).
1
1
3. Gilheany, D. G.; Mitchell, C. M. In The Chemistry of Organophosphorus Compounds; Hartley, F. R., Ed.; John Wiley &
Sons: Chichester, 1990; Vol. 1.
4. A typical preparation is given for tris(4-tridecafluorohexylphenyl)phosphine. A mixture of tris(4-tridecafluorohexyl-
phenyl)phosphine oxide (2.465 g, 2.0 mmol), trichlorosilane (1.355 g, 10 mmol), triethylamine (1.518 g, 15 mmol) and
3
toluene (20 ml) was stirred at reflux for 6 h under nitrogen. After cooling to room temperature, saturated NaHCO aqueous
solution (1 ml) was added. The mixture was stirred for 5 min at room temperature, filtered through a pad of alumina,
washed with toluene (3×20 ml) and evaporated under reduced pressure to give the desired compound as white solids
(2.384 g, 98%). This and all the other compounds given in Table 2 have been characterised by NMR, MS and elemental
analysis or by comparison with authentic samples.