Synthesis of biphenyl-based phosphines by Suzuki coupling

Article abstract of DOI:10.1016/S0040-4039(01)01981-5

A series of phosphine oxides has been synthesised by the palladium-catalysed Suzuki coupling of arylboronic acids with OPPh₂(o-C₆H₄Br). On reduction with trichlorosilane, functionalised, biphenyl-based phosphine ligands were obtained in good yields. Our preliminary results indicate these ligands to be effective for palladium-catalysed C-C coupling reactions including the formation of their own oxides.

Full text of DOI:10.1016/S0040-4039(01)01981-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 9085–9088
Synthesis of biphenyl-based phosphines by Suzuki coupling
Colin Baillie, Weiping Chen and Jianliang Xiao*
Leverhulme Centre for Innovative Catalysis, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
Received 25 September 2001; accepted 19 October 2001
Abstract—A series of phosphine oxides has been synthesised by the palladium-catalysed Suzuki coupling of arylboronic acids with
OPPh2(o-C6H4Br). On reduction with trichlorosilane, functionalised, biphenyl-based phosphine ligands were obtained in good
yields. Our preliminary results indicate these ligands to be effective for palladium-catalysed C–C coupling reactions including the
formation of their own oxides. © 2001 Elsevier Science Ltd. All rights reserved.
Phosphines play an extremely important role in homo-
geneous catalysis.1,2 Those that possess novel electronic
and steric properties and functional groups are of par-
ticular importance, as they can effect unusual activities
and selectivities in metal-catalysed reactions in soluble
or supported forms. Amidst such phosphines, those
containing 2-biphenyl units have recently been shown
to be effective ligands in a number of metal-catalysed
reactions, such as asymmetric hydrogenation,3 allylic
alkylation,4 hydroformylation5 and CꢀX (X=C, N, O)
bond forming reactions.6–11 Worth noting is their out-
standing performance in effecting palladium-catalysed
C–X coupling reactions. In fact, bulky, biphenyl-based
phosphines represent one of the most effective classes of
ligands identified so far for such reactions. These phos-
phines are most often prepared by using Grignard and
lithium reagents.4–11 More recently, Buchwald has
reported a much-simplified synthesis of alkylphosphino-
biphenyl ligands on the basis of the reaction of aryl
magnesium halides with benzyne, followed by the addi-
tion of a chlorodialkylphosphine.12
properties such as H2O and supercritical CO2.13,14 One
methodology utilises the palladium-catalysed Heck
reaction of haloarylphosphine oxides OPPh3−n(p-
C6H4Br)n with olefinic substrates,13 while the other
involves the copper-mediated coupling of the same
oxides with perfluoroalkyl iodides.14 In both cases, the
free phosphines are obtained in excellent yields by
reduction with a chlorosilane and/or hydrogen. With
biphenyl-based phosphine ligands in mind, we have
extended these methodologies for the preparation of
diphenylphosphinobiphenyl derivatives, employing the
Suzuki coupling of OPPh2(o-C6H4Br) 1 with various
arylboronic acids 2, followed by reduction with
trichlorosilane to give the free phosphines 4 (Scheme 1).
While the Suzuki coupling is one of the most useful
routes for the synthesis of biaryls, it has rarely been
used for the direct preparation of phosphine ligands.15
Our method would provide an easy entry to function-
alised biphenyl-based phosphines, as the Suzuki chem-
istry is known to be tolerant of various functionalities.
The details of the method are herein described.
We have recently reported two simple methods for the
synthesis of substituted arylphosphine ligands applica-
ble to catalysis in solvents of widely differing solubility
Our synthesis of the phosphines 4 starts with the Suzuki
coupling of 1 and 2, which leads to the phosphine
O
O
PPh2
PPh2
PPh2
Ar
HSiCl3
Pd / PPh3
+
Ar-B(OH)2
Br
Ar
NEt3
K3PO4
Dioxane
105 oC
Toluene
120 oC
1
2
3
4
Scheme 1. Synthesis of biphenyl-based phosphines via Suzuki coupling.
Keywords: phosphine ligands; biphenyl; Suzuki coupling; C–C coupling; 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)01981-5

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C. Baillie et al. / Tetrahedron Letters 42 (2001) 9085–9088
oxides 3.16 The coupling reaction was conducted with
equimolar amounts of the aryl halide 1 and an aryl
boronic acid 2 and 2 equiv. of a base (K3PO4) in
dioxane at 105°C. The palladium catalyst was formed
in situ from Pd(dba)2 and 4 equiv. of PPh3. Table 1
summarises the results obtained. The ortho-positioned
OPPh2 moiety in 1 is considerably more bulky than
most other ortho substituents encountered in Suzuki
coupling reactions, and as such one may expect the
coupling of 1 with 2 to be difficult when particularly a
ligand such as PPh3 is to be used, which is neither
electron-rich nor bulky in comparison with PR3 (R=
Cy, t-Bu) or those based on biphenyls.6–11,17 PPh3 was
chosen as the ligand as it is the most convenient source
of phosphine due to its ready availability and ease of
handling. As can be seen, 1 couples readily under the
aforementioned conditions with phenylboronic acid 2a
as well as meta and para substituted aryl boronic acids
Table 1. Suzuki coupling of OPPh2(o-C6H4Br) 1 with arylboronic acids 2a

C. Baillie et al. / Tetrahedron Letters 42 (2001) 9085–9088
Ph2P
Ph2P
9087
Ph2P
OMe
SMe
4a, 75%
4g, 74%
4h, 78%
Ph2P
Ph2P
Me
4i, 71%
4j, 70%
Scheme 2. Isolated biphenyl-based phosphines along with yields.18
2b–f to give the expected biaryls in good yields, regard-
less of the nature of the substituents at 2 (entries 1–4).
The coupling of 1 with the halo substituted aryl boronic
acids 2e or 2f was carried out by slow introduction of
the latter via a dropping funnel. Directly mixing 1 and
2e or 2f resulted in lower yields, probably due to the
boronic acid self-coupling and/or coupling with the
product. The presence of the functional groups should
make phosphines derived from these oxides easily sup-
portable onto solid surfaces or polymers. As with other
Suzuki reactions, the coupling of 1 was significantly
more difficult with boronic acids containing ortho sub-
stituents to give di-ortho-substituted biaryls (entries
7–10). The yields given in Table 1 were obtained with
extra addition of boronic acid during the reaction and
prolonged reaction time. P(tBu)3 was also examined for
the reaction of 1 with 2-methoxyphenylboronic acid 2g
and 2-methylthiophenylboronic acid 2h, as it had been
reported to outperform PPh3 in the cross-coupling of
aryl chlorides and aryl boronic acids, and to be tolerant
of ortho substitution in both substrates.17 However, the
reported conditions for our reactions gave lower yields
(71% for 2g and 54% for 2h) than those obtained with
PPh3. This may partly be due to P(tBu)3 being sterically
too demanding. Fu has observed that the sterically less
hindered PCy3 is more effective than P(tBu)3 in the
Suzuki coupling of aryl chlorides that leads to tri-ortho-
substituted biaryls.17
replacing PPh3 with 4a in the coupling of OPPh2(o-
C6H4Br) 1 and phenylboronic acid 2a afforded an 84%
conversion of 1 to 3a, the oxide of 4a, in a 6 h reaction
time under the conditions described for PPh3. When the
sterically more demanding 2-methoxyphenylboronic
acid 2g was coupled to 1 in the presence of Pd-4a, an
84% conversion of 1 to 3g was observed after 24 h.
More interestingly, Pd-4i [0.1 mol% Pd(dba)2, 4 equiv.
of 4i] is effective in catalysing the coupling of the
electron-rich 4-bromotoluene with phenylboronic acid,
furnishing 4-methylbiphenyl in 92% isolated yield at
60°C in a 24 h reaction time.
We have previously shown that the Heck and related
reactions can provide a powerful route to arylphosphi-
nes with special solubility properties.13,14,19 The work
presented here shows that functionalised biphenyl-
based phosphine ligands can readily be accessed by
another class of catalytic CꢀC bond formation reac-
tions, namely Suzuki coupling reactions. Research is
underway to test the applicability of these ligands in
catalysis.
Acknowledgements
We thank the EPSRC and the industrial partners (Syn-
etix, Johnson Matthey, Catalytica, Air Products, Syn-
troleum) of the Leverhulme Centre for Innovative
Catalysis for financial support. J.X. is particularly
grateful to Synetix for the support of a Readership.
The free phosphines 4 were obtained from the oxides 3
by reduction with trichlorosilane.18 The reaction was
carried out by simply heating
a mixture of 3,
trichlorosilane and triethylamine in toluene at 120°C
for a few hours, affording the biaryl-based phosphines
4 in crystallised forms with good yields. Some examples
are shown in Scheme 2. Interestingly, 4 could also be
obtained by coupling 2 with a haloarylphoshine instead
of its oxide in the presence of a palladium catalyst
without additional ligands. Thus, (2-bromophenyl)-
diphenylphosphine PPh2(o-C6H4Br) coupled with 2a
(3% Pd(dba)2, 12 h, 105°C), yielding 4a in 79% yield
according to 31P NMR. This method could obviate
the need for reduction by trichlorosilane if proven to
be generally applicable.
References
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C. Baillie et al. / Tetrahedron Letters 42 (2001) 9085–9088
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nitrogen, to which were added trichlorosilane (0.57 ml,
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mixture was stirred at 120°C under argon for 6 h. After
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aqueous solution (1 ml) was added. The mixture was
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16. A typical procedure is given for 3a. To a Schlenk tube
were charged OPPh2(o-C6H4Br) 1 (0.500 g, 1.40 mmol)
and phenylboronic acid 2a (0.171 g, 1.40 mmol) together
with Pd(dba)2 (0.024 g, 0.04 mmol), PPh3 (0.044 g, 0.17
mmol) and K3PO4 (0.594 g, 2.80 mmol) in 5 ml of
dioxane under an atmosphere of argon. The Schlenk tube
was stirred at 105°C overnight. After cooling to room
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