Improved synthesis of monodentate and bidentate 2- and 3-pyridylphosphines

Article abstract of DOI:10.1016/j.tetlet.2007.02.127

Tris(pyridyl)phosphines (2- and 3-pyridyl) and 1,2-bis(di-3-pyridylphosphino)ethane were synthesized in 70-75% yield using a Grignard reagent. The product could be efficiently isolated by solid-liquid extraction with diethylamine.

Full text of DOI:10.1016/j.tetlet.2007.02.127

Tetrahedron Letters 48 (2007) 2999–3001
Improved synthesis of monodentate and bidentate
2- and 3-pyridylphosphines
Alexander M. Kluwer, Irshad Ahmad and Joost N. H. Reek*
Van’t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166,
1018 WV Amsterdam, The Netherlands
Received 16 January 2007; revised 23 February 2007; accepted 27 February 2007
Available online 2 March 2007
Abstract—Tris(pyridyl)phosphines (2- and 3-pyridyl) and 1,2-bis(di-3-pyridylphosphino)ethane were synthesized in 70–75% yield
using a Grignard reagent. The product could be efficiently isolated by solid–liquid extraction with diethylamine.
Ó 2007 Elsevier Ltd. All rights reserved.
Complexes of transition metals with pyridylphosphine
ligands have been thoroughly investigated because of
their interesting coordination behavior and catalytic
activity.1–6 Particular attention has been directed
to the monopyridyl PPh2(2-pyridyl), which has been
successfully used in the construction of homo- and het-
erometallic complexes. Recently, the tris(pyridyl)phos-
phines (both 3- and 4-pyridyl, 1 and 2, respectively)
have been recognized as valuable building blocks for
the construction of supramolecular structures. Particu-
larly, the ability of such compounds to coordinate to
hard metals via the pyridyl nitrogen and to a catalytically
active transition metal via the phosphorus makes them
ideal for building heterometallic architectures (Scheme
1).7–9 This approach has been explored by our group to
effectively encapsulate transition metal catalysts by, for
example, Zn(II) meso-porphyrins and Zn(II)salphens,
which has dramatic consequences for the activity
(increases 10-fold) and the selectivity of the catalyst.10
In addition, the preparation of supramolecular bidentate
ligands by selective self-assembly has been used to pre-
pare significantly large catalyst libraries, enabling a fast
and efficient catalyst screening simply by changing the
building blocks of the supramolecular bidentate.11–15
N
N
N
N
N
N
N
Zn
N
N
[M]
P
Zn(II)TPP + P(3-Py)3
N
M
N
N N
Zn
N N
Scheme 1. Encapsulation of transition metal catalyst ([M]) by Zn(II)(meso-tetraphenyl porphyrine).
Keywords: Synthesis; Grignard reaction; Pyridylphosphine; Monodentate; Bidentate; 2-Pyridyl; 3-Pyridyl.
*
Corresponding author. Tel.: +31 (0)20 5256437; fax: +31 (0)20 5255604; e-mail: reek@science.uva.nl
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.02.127

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A. M. Kluwer et al. / Tetrahedron Letters 48 (2007) 2999–3001
The syntheses of pyridylphosphines as published by
Berners-Price et al.,16 employ an organolithium com-
pound to prepare the pyridyl lithium reagent, which is
subsequently allowed to react with a PCl-compound
(PCl3 or Cl2PCH2CH2PCl2) to obtain the corresponding
pyridylphosphine. Essential in the lithiation step are
maintaining the low reaction temperature (À110 °C)
and short reaction times to prevent isomerization
of the parent pyridyl lithium compound. Besides the
desired product also butyl phosphine compounds
are formed, which need to be separated afterwards by
column chromatography. According to the authors,
multiple columns are required to obtain the pure
tris(3-pyridyl)phosphines (isolated yield 45%).16
sium salts (by Na2CO3, NaOH or NH4OH) or the
chelating of the Mg2+-ions by, for example, Na2EDTA.
None of these attempts were successful since, in every
case, new (hard) cations are introduced that have a high
tendency to coordinate to the pyridyl nitrogens. These
complexes are too water soluble to extract with an
organic solvent like dichloromethane or chloroform.
A suitable solution to this problem is the solid–liquid
extraction of the phosphine (and phosphine oxide if
formed) with diethylamine (Et2NH) directly from the
quenched and dried reaction mixture. The Et2NH can
successfully compete for the coordination sphere of the
main group metal thereby liberating the desired product.
The solubility of the Mg2+-salts in pure Et2NH is negli-
gible and thus only organic products are collected. Since
diethylamine is relatively cheap, has a low boiling point,
and displays a relative low toxicity, it is ideal for such
extractions and can be easily recycled. Of course, the
formed phosphine oxide is also in the Et2NH phase
but this can be simply removed by flash column chroma-
tography. Using this route, the reaction can be per-
formed on a multi-gram scale with an overall yield of
75%. This procedure has also been applied to the synthe-
sis of 1,2-bis(di-3-pyridylphosphino)ethane and tris(2-
pyridine)phosphine and these compounds were isolated
respectively in 70% and 71% yield.
To circumvent these intensive purification steps and to
satisfy the need for larger quantities of the pyridylphos-
phine compounds, a different procedure was explored
using the Grignard reaction. Although some reports
have appeared for the preparation of such compounds
employing a Grignard reagent, the degree of success var-
ies.2 Particularly, the (3-pyridyl)- and (4-pyridyl)phos-
phine compounds are notoriously difficult to isolate.
Here, we report a general route toward the synthesis
of pyridylphosphines using Grignard reagents, giving
high yields of the desired product. Since less stringent
reaction conditions are required, and the work-up is
considerably facilitated by reducing the number of
byproducts, this reaction can easily be performed on a
multigram scale.
An optimized synthesis of pyridylphosphines via a Grig-
nard reaction has been reported. As is corroborated by
the many literature reports, Mg-pyridyl reagents have
a low tendency for isomerization and thus tolerate less
stringent reaction conditions. The synthetic strategy
and work-up procedure, that involves solid–liquid
extraction with diethylamine, can be easily extended to
other pyridylphosphines.
For the preparation of the Grignard reagent, the pure 3-
bromopyridine was added to a THF solution containing
activated magnesium. Subsequently, the organomagne-
sium intermediate was allowed to react at À78 °C with
PCl3, forming the desired product (Scheme 2). An
attempt to prepare a more pure Grignard reagent
(without Wurtz-coupling product) based on the method
often employed in dendrimer synthesis17 yielded only a
small amount of Grignard reagent, probably due to
the low reactivity of bromopyridine.
Acknowledgments
We are thankful to the National Research School Com-
bination Catalysis (NRSC-C) and the Dutch Organiza-
tion for Scientific Research (NWO) for support.
From earlier studies it is known that the introduction of
pyridyl groups to phosphines increases the solubility in
aqueous solution of the corresponding phosphine
ligand.18 The presence of hard cations (such as Mg2+
)
Supplementary data
strongly increases the water-solubility of these com-
pounds. Due to the stronger coordination of the desired
product to the magnesium salts (compared to Li-salts)
present in the reaction mixture, the standard work-up
procedure (extraction with CH2Cl2 from aqueous layer)
failed and a new one was developed. Several approaches
were investigated such as the precipitation of the magne-
General experimental procedures, 1H, 13C, 31P NMR
spectra and GC–MS data are available. Supplementary
data associated with this article can be found, in the
online version, at doi:10.1016/j.tetlet.2007.02.127.
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