Nickel-catalyzed reductive coupling of chlorodiphenylphosphine with aryl bromides into functionalized triarylphosphines

Article abstract of DOI:10.1016/S0040-4020(03)01180-3

Functionalized triarylphosphines are obtained with good yields in a one-step reaction of an equimolar mixture of chlorodiphenylphosphine and an aromatic bromide in NMP or DMF at 110°C in the presence of zinc dust and a catalytic amount of NiBr₂

Full text of DOI:10.1016/S0040-4020(03)01180-3

Tetrahedron 59 (2003) 7497–7500
Nickel-catalyzed reductive coupling of chlorodiphenylphosphine
with aryl bromides into functionalized triarylphosphines
*
´ ´
Erwan Le Gall, Michel Troupel and Jean-Yves Nedelec
`
Laboratoire d’Electrochimie, Catalyse et Synthese Organique, LECSO, CNRS GLVT, UMR 7582, 2-8 rue Henri Dunant,
94320 Thiais, France
Received 27 February 2003; revised 3 July 2003; accepted 28 July 2003
Abstract—Functionalized triarylphosphines are obtained with good yields in a one-step reaction of an equimolar mixture of
chlorodiphenylphosphine and an aromatic bromide in NMP or DMF at 1108C in the presence of zinc dust and a catalytic amount of
NiBr2(bpy). A possible catalytic pathway is discussed.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
moderate yields from aryl bromides and with good yields
from aryl triflates. These substrates are coupled with
chlorodiphenylphosphine in a one-pot reaction using zinc
dust as reductant. More recently, NiCl2(PPh3)2 was found to
be an effective catalyst towards phosphination of biaryl
triflates with chlorodiphenylphosphine.7 In a related
approach, a group in this laboratory showed that such a
reductive cross-coupling between an aryl bromide or an
heteroaromatic chloride and Ph2PCl can be achieved by an
electrochemical way where the catalyst is0 generated by
electroreduction of NiBr2(bpy) (bpy¼2,2 -bipyridine).8
This method is however rather delicate to perform since
its requires a well controlled addition rate of Ph2PCl all over
the electrolysis in order to avoid side reactions. Even in
optimized reaction conditions, yields in arylphosphine are
only moderate.
The modern synthetic chemistry counts increasingly on
catalysis to obtain more efficient and clean procedures. In
the field of homogeneous catalysis, tertiary arylphosphines
form an important class of ligands of transition metals
which has attracted considerable interest in the past few
decades. The presence of functional groups on at least one
aryl moiety can obviously offer the advantage of fitting the
catalytic properties of a phosphine-ligated metallic center.
However, the preparation of functionalized phosphines
excludes the usual methods of synthesis based on reactions
involving aryllithium or aryl Grignard reagents in the case
of base-sensitive functional groups. Since the pioneering
work of Stille,1 which reported in 1987 a palladium-
catalyzed coupling reaction between functionalized aryl
iodides and either trimethylstannyl- or trimethylsilyl-
diphenylphosphine, several studies have been devoted to
transition metal-catalyzed cross-coupling reactions leading
to arylphosphines. For example, aryl triflates react with
diphenylphosphine in the presence of Pd(OAc)2 and dppb
(dppb¼bis-diphenylphosphinobutane),2 or in the presence
of NiCl2(dppe) (dppe¼bis-diphenylphosphinoethane).3
Recent papers relate that triphenylphosphine can also be
used in order to obtain aryldiphenylphosphine through
Pd-catalyzed couplings with either aryltriflates4 or aromatic
bromides.5 Interestingly, Laneman et al.6 reported some
years ago that the nickel complex NiCl2(dppe) is also an
efficient catalyst for the synthesis of triarylphosphines, with
We then decided to reinvestigate the chemical approach on
the basis of both Laneman’s work and our electrochemical
investigations. Actually, it is known that the reduction of a
NiII-dppe salt leads to a zerovalent complex Ni0(dppe)
which is very reactive towards carbon–halogen bonds.9 On
the contrary, the stable Ni0(dppe)2 complex is quite unreac-
tive.10 It may form by disproportionation between two
Ni0(dppe), thus accounting for a loss of the catalyst in the
form of nickel metal. Such a drawback does not exist when the
ligand is bipyridine (bpy), since zerovalent nickel reacts with
aryl halides, even in the presence of an excess of bpy.11
We report in this paper our results on the reductive coupling
between functionalized aryl bromides and Ph2PCl by a
chemical reaction employing zinc as0 the reductant and
complexes of nickel associated with 2,2 -bipyridine (bpy) or
2,20-dipyridylamine (dpa) as catalysts.
Keywords: triarylphosphine; chlorodiphenylphosphine; aromatic bromide;
reductive cross-coupling; nickel-bipyridine catalysis.
*
Corresponding author. Tel.: þ33-149781125; fax: þ33-149781148;
e-mail: legall@glvt-cnrs.fr
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)01180-3

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E. Le Gall et al. / Tetrahedron 59 (2003) 7497–7500
2. Results and discussion
slowed down. The reaction conditions corresponding to
entry 8 of Table 1 were thus considered as being
satisfactory.
Our first goal was the synthesis of m-CF3–C6H4PPh2
(product 1a) from m-CF3–C6H4Br and ClPPh2, and we
conductednew experimentseitherinDMForNMP(N-methyl-
pyrrolidinone), and using nickel complexes associated to
bidentate nitrogenous ligands, either bpy or dpa instead of
dppe, as catalyst precursor. In a typical experiment, an
equimolar mixture of m-CF3–C6H4Br and ClPPh2 was
heated at 1108C in DMF or NMP, in the presence of a slight
excess of zinc and a catalytic amount of NiBr2(bpy) or
NiBr2(dpa). The reactions were conducted until more than
95% of the aryl halide was consumed. The results are
reported in Table 1.
We then extended this method to other substituted aryl
bromides. In NMP with a 2.5% ratio of NiBr2(bpy), the
cross-coupling with chlorodiphenylphosphine was per-
formed with moderate to good yields by heating at 1108C
an equimolar mixture of both reactants and zinc dust.
Results are reported in Table 2.
It can be seen that the position of the substituent has a high
influence on the efficiency of the cross-coupling reaction.
Indeed, meta- and para-trifluoromethyl-bromobenzene fur-
nishes the coupling products in high yields (entries 1 and 3
of Table 2) whereas ortho-trifluoromethyl-bromobenzene
leads to only 30% of the related triarylphosphine (entry 2 of
Table 2), several by-products being formed along with.
When very reactive para-substituted aryl bromides are used,
the amount of catalyst has to be reduced to 1.25% and even
in these conditions, the reaction proceeds very fast (entries 7
and 8 of Table 2). We also found that the oxide is easily
formed when the functional group on the starting aryl halide
is electron-donating like the methoxy group (Table 2, entry
9). These results also show again that the use of DMF as
solvent and NiBr2(dpa) as catalyst (Table 2, entries 10–12)
leads to significant amounts of the product in the form of the
oxide.
It is worth noting that the yields in 1a are higher when NMP
is used as solvent instead of DMF, and also with NiBr2(bpy)
(entries 1 and 2 of Table 1) as catalyst rather than
NiBr2(dpa) (entries 3 and 4 of Table 1). Both catalysts are
indeed efficient. However, if the Ni-dpa system allows
rather higher yields (entries 3 and 4 of Table 1), it also tends
to favor the partial oxidation of the phosphine 1a into the
corresponding oxide 1b during the work up. A crucial
experimental parameter is the reaction temperature. Indeed,
two experiments corresponding to entries 2 and 4 of Table 1
were performed at 808C instead of 1108C. After an
overnight reaction, the aryl bromide was not fully consumed
and the yield in coupling products (1aþ1b) was only 20–
25%. On the other hand, no difference in the yield was
observed when zinc was added either after cooling the
solution at 5–108C, as recommended with the Ni-dppe
catalyst,6 or at room temperature, this being followed by
immediate heating up to 1108C. Other parameters were
studied, while keeping the following unchanged, i.e.
reaction temperature at 1108C, NiBr2(bpy) as the catalyst
precursor, and NMP as the solvent. As shown in Table 1,
entries 5–8, the reaction remained very efficient when the
concentration of both reactants was increased up to
2 mol L21 while lowering the molar ratio of the catalyst
to 2.5%. Even with 1.25% of NiBr2(bpy) (entry 9 of
Table 1), the yield was high, though the reaction rate was
To our knowledge, the mechanism of this nickel-catalyzed
reductive cross coupling between chlorodiphenylphosphine
and an aryl halide has not been described. We propose the
following catalytic mechanism (Scheme 1), notably on the
basis of previous electroanalytical studies.
Since no coupling product is obtained in the absence of
nickel complexes, this indicates that the reaction proceeds
via an homogeneous catalysis involving organonickel
complexes. This catalytic cycle is initiated by the zinc
reduction of the divalent nickel precursor into a zerovalent
complex, either Ni0(bpy) or Ni0(dpa) in this work, or
Table 1. Nickel-catalyzed reductive cross-coupling between chlorodiphenylphosphine and m-trifluoromethylbromobenzene
Entry
Solvent
Volume (mL)
Catalyst (mol%)
Reaction time (h)
GC Yield (%)
1a 1b
Isolated (%)
1a
1
2
3
4
5
6
7
8
9
DMF
NMP
DMF
NMP
NMP
NMP
NMP
NMP
NMP
20
20
20
20
10
7.5
7.5
5
NiBr2(bpy) (5)
NiBr2(bpy) (5)
NiBr2(dpa) (5)
NiBr2(dpa) (5)
NiBr2(bpy) (5)
NiBr2(bpy) (5)
NiBr2(bpy) (2.5)
NiBr2(bpy) (2.5)
NiBr2(bpy) (1.25)
4
1
3
60
70
60
75
88
85
84
95
80
5
10
20
24
5
6
6
4
6
–
68
55
63
–
–
–
2
1.25
0.75
1.5
2
86
–
5
4
Standard reaction conditions: Ph2PCl (10 mmol), ArBr (10 mmol), Zn dust (16 mmol), 1108C under argon.

E. Le Gall et al. / Tetrahedron 59 (2003) 7497–7500
7499
Table 2. Nickel-catalyzed reductive cross-coupling between chlorodiphenylphosphine and functionalized aryl bromides
Entry
FG
Solvent
Catalyst (mol%)
Reaction time (h)
Product and isolated yield (%)
1
2
3
4
5
6
7
8
9b
10
11
12
m-CF3
o-CF3
p-CF3
m-CN
m-CO2Et
p-CO2Et
p-COMe
p-CHO
p-MeO
m-CF3
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
DMF
DMF
DMF
NiBr2(bpy) (2.5%)
NiBr2(bpy) (2.5%)
NiBr2(bpy) (2.5%)
NiBr2(bpy) (2.5%)
NiBr2(bpy) (2.5%)
NiBr2(bpy) (2.5%)
NiBr2(bpy) (1.25%)
NiBr2(bpy) (1.25%)
NiBr2(bpy) (2.5%)
NiBr2(dpa) (5%)
2
4
3
1.25
3
3
1
0.5
3
3
3
1a
2a
3a
4a
5a
6a
7a
8a
9a
1a
4a
5a
m-F3C–C6H4PPh2
o-F3C–C6H4PPh2
p-F3C–C6H4PPh2
m-NC–C6H4PPh2
m-EtO2C–C6H4PPh2
p-EtO2C–C6H4PPh2
p-MeOC–C6H4PPh2
p-HOC–C6H4PPh2
p-MeO–C6H4PPh2
m-F3C–C6H4PPh2
m-NC–C6H4PPh2
m-EtO2C–C6H4PPh2
86
30
75
73
69
76
75
70a
49c
55c
62c
61c
m-CN
m-CO2Et
NiBr2(dpa) (5%)
NiBr2(dpa) (5%)
3
Standard reaction conditions: solvent (5 mL), Ph2PCl (10 mmol), ArBr (10 mmol), Zn dust (16 mmol), 1108C, under argon.
GC yield, the coupling product leads to degradation products during work-up.
a
b
The starting compound was p-MeO–C6H4I.
Actually, large amounts of phosphine oxides were detected in the crude mixture.
c
Scheme 1. A possible catalytic mechanism of the Ni-catalyzed cross-coupling reaction between ClPPh2 and an aromatic bromide.
Ni0(dppe) in Laneman’s work.6 These zerovalent nickel
complexes are known to react by oxidative addition with
aryl halides (ArX) to give the corresponding s-aryl-nickel
complex, ArNiIIXL.11,12 At this stage, two routes can be
envisaged. Either ClPPh2 can react with ArNiX to yield the
aimed product, or a transmetallation reaction first occurs
between ArNiX and Zn2þ cations thus providing ArZnX.13
Thus, as demonstrated elsewhere,14 the aryl phosphine
would be obtained by coupling of an organozinc intermedi-
ate with the electrophile ClPPh2. However, in the absence of
ArBr, we have found that the addition of NiBr2(bpy) and
zinc dust into a solution of ClPPh2 induces the transform-
ation of the chlorophosphine into unidentified product(s).
Therefore, we can assume that the zerovalent complex
Ni0(bpy) can also reacts with ClPPh2, either by electron
transfer or by oxidative addition with the P–Cl bond but we
have any information on a possible mechanism leading to a
coupling product with an aryl halide by this way.
main features of this versatile method are the simplicity of
the reaction conditions and the compatibility with various
functional groups. We propose a possible catalytic mech-
anism for this Ni-bpy catalyzed reaction.
4. Experimental
Solvents (NMP or DMF in analytical grades) and starting
materials were purchased from commercial suppliers and
used without further purification. The catalytic precursor
NiBr2(bpy) was prepared according to a reported method15
by precipitation in absolute ethanol of an equimolar mixture
of NiBr2·xH2O and 2,20-bipyridine, filtration, ethanol
rinsing and drying. The same method was applied to the
synthesis of the complex NiBr2(dpa). Chromatographic
purifications were realized using Merck 60 ACC (70–200
mesh) silica gel.
4.1. Typical experimental procedure for a
Ni-catalyzed cross-coupling reaction between
chlorodiphenylphosphine and an aromatic bromide
3. Conclusion
We have demonstrated several examples of cross coupling
reactions between commercially available chlorophosphine
and aromatic bromides. Functionalized triarylphosphines,
potentially useful as ligands in homogeneous catalysis, are
obtained with good yields by this way which uses zinc as a
cheap reductant and NiBr2(bpy) as an efficient catalyst. The
A mixture of ArBr (10 mmol), chlorodiphenylphosphine
(1.8 mL, 10 mmol) and either NiBr2(bpy) (93 mg,
0.25 mmol) or NiBr2(dpa) (97 mg, 0.25 mmol) were
dissolved in 5 mL NMP (N-methyl-pyrrolidinone). Zinc
dust (1.1 g, 16 mmol) was added portion wise in a few

7500
E. Le Gall et al. / Tetrahedron 59 (2003) 7497–7500
minutes. The solution was then heated under argon up to
1108C until GC analysis of samples indicated the quasi
consumption of ArBr. The solution was allowed to cool at
room temperature and the solvent was evaporated under a
reduced pressure in the presence of celite. The triarylphos-
phine was recovered by a chromatographic purification on a
silica gel (Merck 60 ACC, 70–200 mesh) column and
elution with a suitable pentane/diethyl ether mixture.
solid; 1H NMR, d (ppm): 7.86 (m, 2H), 7.40–7.25
(m, 12H), 2.56 (s, 3H); 31P NMR, d (ppm): 29.95; MS,
m/z (relative intensity): 304 (M, 100), 261 (M243, 16), 225
(M279, 10), 183 (M2121, 52).
4.2.8. (4-Methoxyphenyl)-diphenylphosphine 9a.1 White
solid; 1H NMR, d (ppm): 7.22–7.14 (m, 12H), 6.77 (m, 2H),
3.66 (s, 3H); 31P NMR, d (ppm): 212.03; MS, m/z (relative
intensity): 292 (M, 100), 277 (M215, 9), 213 (M279, 19),
199 (M293, 11), 184 (M2108, 38), 170 (M2122, 9), 138
(M2154, 9), 108 (M2184, 9).
4.2. Analytical data
GC analyses were performed on a 5 m CPSIL-5CB column
using a Varian 3400 CX chromatograph. Mass spectra were
recorded on a Finnigan GC/MS GCQ spectrometer. 1H
(200 MHz), 31P (81 MHz) and 19F (188 MHz) NMR spectra
were recorded in CDCl3 on a Bruker AC200 spectrometer.
Analytical data of synthesized triarylphophines fit with
analytical data found in given references.
Acknowledgements
The authors thank Rhodia Recherches for financial support
of this work.
4.2.1. [(3-Trifluoromethyl)phenyl]-diphenylphosphine
1
1a.16,17 Pale yellow viscous oil; H NMR, d (ppm): 7.80–
References
7.10 (m, 14H); 31P NMR, d (ppm): 29.99; 19F NMR, d
(ppm): 262.38; MS, m/z (relative intensity): 330 (M,100),
251 (M279, 19), 203 (M2127, 18), 183 (M2147, 48), 108
(M2222, 22).
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4.2.2. [2-(Trifluoromethyl)phenyl]-diphenylphosphine
1
2a.18 White solid; H NMR, d (ppm): 7.65–7.55 (m, 1H),
7.20–7.05 (m, 13H); 31P NMR, d (ppm): 216.15 (q,
J¼47 Hz); 19F NMR, d (ppm): 256.45 (d, J¼47 Hz); MS,
m/z (relative intensity): 330 (M,100), 241 (M289, 60), 183
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4.2.3. [4-(Trifluoromethyl)phenyl]-diphenylphosphine
1
3a.1 Pale yellow viscous oil; H NMR, d (ppm): 7.53 (m,
2H), 7.41–7.27 (m, 12H); 31P NMR, d (ppm): 210.33; 19
F
´ ´ ´
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(M,100), 251 (M279, 20), 203 (M2127, 18), 183 (M2147,
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10. Sock, O.; Troupel, M.; Perichon, J.; Chevrot, C.; Jutand, A.
4.2.4. (3-Cyanophenyl)-diphenylphosphine 4a.19 Pale
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11. (a) Troupel, M.; Rollin, Y.; Sock, O.; Meyer, G.; Perichon, J.
New J. Chem. 1986, 10, 593–599. (b) Rollin, Y.; Troupel, M.;
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brown solid; H NMR, d (ppm): 7.80–7.20 (m, 14H); 31P
´
NMR, d (ppm): 210.04; MS, m/z (relative intensity): 287
(M, 100), 208 (M279, 33), 183 (M2104, 36), 108 (M2179,
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´ ´ ´
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4.2.5. Ethyl 3-(diphenylphosphino)benzoate 5a.8 Pale
1
´ ´
´
yellow viscous oil; H NMR, d (ppm): 8.30–8.10 (m, 2H),
7.70–7.35 (m, 12H), 4.48 (q, 3J¼7.1 Hz, 2H), 1.49
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3
(t, J¼7.1 Hz, 3H); 31P NMR, d (ppm): 210.44; MS, m/z
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(M2153, 49).
15. Uchino, M.; Asagi, K.; Yamamoto, A.; Ikeda, S. J. Organomet.
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4.2.6. Ethyl 4-(diphenylphosphino)benzoate 6a.8 Pale
yellow viscous oil; 1H NMR, d (ppm): 8.12 (m, 2H),
7.60–7.35 (m, 12H), 4.48 (q, 3J¼7.1 Hz, 2H), 1.48
16. Bethell, D.; Bourne, R.; Kasran, M. J. Chem. Soc., Perkin
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3
(t, J¼7.1 Hz, 3H); 31P NMR, d (ppm): 210.18; MS, m/z
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4.2.7. (4-Acetylphenyl)-diphenylphosphine 7a.1 White