Synthesis and Reactivity of Tris(Hydroxymethyl)Phosphine-Mimicking Nonsymmetrical Diphosphine Ligands

Article abstract of DOI:10.1080/10426507.2014.983597

As part of a study to obtain well-defined tris(hydroxymethyl)phosphine (THP)-inspired ligands, a new nonsymmetrical diphosphine featuring two hydroxymethyl functional groups on one phosphine terminus has been synthesized. A double formylation reaction was employed to effect the hydroxymethylation of the primary phosphine function in Ph₂P(CH₂)₂PH₂ and furnish the target bis(hydroxymethyl)phosphanylethyldiphenylphosphine. Initially, this methodology afforded complex product mixtures whose composition varied according to the reaction solvent, and these are assumed to result from acetalization of excess formaldehyde by the hydroxymethyl groups of the anticipated phosphine. The desired target could be obtained via a borane protection - deprotection pathway or by repeatedly treating the product mixture with H₂O, thereby probably shifting a hemiacetal equilibrium of the phosphine with formaldehyde towards the free hydroxymethyl functionalities.

Full text of DOI:10.1080/10426507.2014.983597

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Synthesis and Reactivity of
Tris(hydroxymethyl)phosphine Mimicking
Nonsymmetrical Diphosphine Ligands
Aike Nijlandab, Steven van Zutphena & Duncan Carmichaelb
a Magpie Polymers, 108 av. Carnot, 77140 Saint-Pierre-lès-Nemours, France
b Laboratoire de Chimie Moléculaire, Ecole Polytechnique, CNRS, 2 route de Saclay, 91128
Palaiseau Cedex, France
Accepted author version posted online: 22 Apr 2015.
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To cite this article: Aike Nijland, Steven van Zutphen & Duncan Carmichael (2015): Synthesis and Reactivity of
Tris(hydroxymethyl)phosphine Mimicking Nonsymmetrical Diphosphine Ligands, Phosphorus, Sulfur, and Silicon and the Related
Elements, DOI: 10.1080/10426507.2014.983597
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Synthesis and Reactivity of Tris(hydroxymethyl)phosphine Mimicking
Nonsymmetrical Diphosphine Ligands
Aike Nijlanda,b, Steven van Zutphena, and Duncan Carmichaelb*
a Magpie Polymers, 108 av. Carnot, 77140 Saint-Pierre-lès-Nemours, France
b Laboratoire de Chimie Moléculaire, Ecole Polytechnique, CNRS,
2 route de Saclay, 91128 Palaiseau Cedex, France
Email: duncan.carmichael@polytechnique.edu
Title for running head: Tris(hydroxymethyl)phosphine Mimicking Nonsymmetrical
Diphosphine Ligand Synthesis
Abstract
As part of a study to obtain well- defined tris(hydroxymethyl)phosphine (THP) -inspired
ligands, a new nonsymmetrical diphosphine featuring two hydroxymethyl functional
groups on one phosphine terminus has been synthesized. A double formylation reaction
was employed to effect the hydroxymethylation of the primary phosphine function in
Ph2P(CH2)2PH2
and
furnish
the
target
bis(hydroxymethyl)phosphanylethylenediphenylphosphine. Initially this methodology
afforded complex product mixtures whose composition varied according to the reaction
solvent, which are assumed to result from acetalisation of excess formaldehyde by the
hydroxymethyl groups of the anticipated phosphine. The desired target could be
obtained via a borane protection – deprotection pathway or by repeatedly treating the
product mixture with H2O, thereby probably shifting a hemiacetal equilibrium of the
phosphine with formaldehyde towards the free hydroxymethyl functionalities.
Keywords: Tris(hydroxymethyl)phosphine, phosphine borane deprotection, phosphine
formylation
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INTRODUCTION
Tris(hydroxymethyl)phosphine (THP) has found uses ranging from flame-
retardants1, biocides2, bleaching and brightness stabilizing agents for pulp3 to highly
selective recovery of precious metals. Being a surrogate of PH3, it also has the
interesting property of being an easily-handled source of phosphorus anion equivalents.
Among the properties that make THP stand out from other phosphine compounds are
its low cost, its relative stability with respect to oxidation under neutral conditions,4 and
its water solubility.5 In principle, such properties might be harnessed to provide catalysts
which are recoverable and/or viable under aqueous conditions, and it is unsurprising
that there has been substantial literature interest in the coordination chemistry of THP.
Successful syntheses of many metal complexes bearing hydroxymethylphosphine
ligands have been reported6 but, generally, their performance in catalytic systems has
been rather disappointing.3,7
In an attempt to investigate what might be compromising these systems, the
coordination chemistry and catalytic behaviour of a series of ethylene bridged
diphosphine ligands are under investigation (Figure 1A). The nonsymmetrical ethylene
bridged 1-diphenylphosphino-2-bis(hydroxymethyl) phosphines depicted in Figure 1B
should provide an easily accessible route to well-defined THP-inspired complexes and
are expected to bind strongly because of the chelate effect.8 This should allow metal-
bound reactivity at the hydroxyalkylphosphine functionality to be studied with little
intervention from processes resulting from P-dissociation.
[Insert Figure 1]
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The successful synthesis of an example of this type of ligand means that the
study of processes such as instability of THP- based catalysts in aqueous medium,
interference by formaldehyde formed by THP deformylation, or the generation of
unstable secondary phosphine species should be facilitated, and allow how such
processes might compromise catalytic processes to be examined.9
RESULTS AND DISCUSSION
The straightforward synthesis of primary-tertiary diphosphine 1 is adapted from
well-described protocols in the literature (Scheme 1).10
[Insert Scheme 1]
Compound 2 (Table 1), which constitutes the formal 1,2-addition product of 1 with
formaldehyde, was chosen as our initial target because the presence of two
hydroxymethyl groups at the same phosphorus centre. This makes the ligand quite
evocative of THP, as well as simplifying the initial stages of the study by avoiding the
the possibility of having several product diastereomers. However, the preparation of
clean samples of this compound by formylation of 1 proved to be less straightforward
than expected. Both paraformaldehyde or a formalin solution can be used as
formaldehyde sources for the formylation of the primary phosphine (Table 1) but, when
paraformaldehyde was used, a large excess of the reagent and elevated temperatures
were required because formaldehyde gas escapes from the reaction mixture under the
harsh conditions required to crack the paraformaldehyde. Following the reaction with
31P NMR showed that the reaction proceeds selectively in boiling THF (Table 1, Entry 1)
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but a polymeric residue of paraformaldehyde was observed on the walls of the reaction
vessel and in the condenser. In addition to underlining why excess reagent is needed,
this probably also explains why the conversion in THF did not proceed beyond 75%.
The primary phosphine was consumed fully under the same conditions in toluene, but
several products that are assumed to result from further evolution of the product
phosphine 2 under the reaction conditions were produced (≥3, Table 1, Entry 2). The
use of formalin as a formaldehyde source for the efficient formylation of primary
phosphines under homogeneous conditions, either in the presence11 or absence12 of a
transition metal catalyst. has been described Katti et al. Under their conditions (ethanol,
room temperature), 1 reacted with an excess of degassed 37% formalin (5 eq.) to give a
full and selective conversion within 2 h (Table 1, Entry 3). In a biphasic system with
diethyl ether and formalin, 1 was fully consumed after 4 hours but in this case, the
presence of at least three distinct species was again observed (Table 1, Entry 4).
Concentration of the ethereal layer in vacuo gave a 31P{1H} NMR spectrum in ethanol
that showed the same major product that was prepared in ethanol under the above
homogeneous conditions (δ -12.8 (d) and -20.8 (d) ppm). Replacing the solvent of the
ethanolic product solution (Table 3, Entry 3) by diethyl ether on the other hand, resulted
in a 31P NMR spectrum showing two compounds to be present in similar amounts.
[Insert Table 1]
To find out what lies behind these observations, we tried to isolate the reaction
products by converting them into their air-stable borane-protected analogs (Scheme 2).
4
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The formylation was performed in ethanol at room temperature as this represents the
most straightforward and in fact fastest method. Redissolution of the concentrated
product solution in CH2Cl2 gave two diphosphines in a ratio that was close to 1:1.
Addtion of BH3·SMe2 (2 equiv.) afforded a mixture of two boranated diphosphines
according to 31P NMR, from which only desired diphosphine-borane 3 (Scheme 2) could
be isolated after column chromatography (50% yield, two broad signals at 23.6 and 18.1
ppm in the 31P{1H} NMR spectrum). The deprotection of this diphosphine-borane was
effected classically according to Livinghouse’s protocol13 upon treatment with HBF4 in
CH2Cl2 followed by addition of degassed water and NaHCO3 subsequently until pH = 6-
7.
[Insert Scheme 2]
This deprotection may seem trivial but seems to be unprecedented for
hydroxymethylphosphine boranes, in spite of being considerably prevelant in the
literature.14 Alternatively, and more conveniently, compound 2 could be isolated directly
and in good yield by washing a solution of the concentrated product mixture (Entry 3,
Table 1) in CH2Cl2 repetitively with H2O, likely to effect deformylation of product
hemiacetals by extraction of formaldehyde into the aqueous layer (85% yield).
To conclude, our preliminary studies indicate that the clean synthesis of chelating
hydroxymethylphosphines, whilst not trivial, can be achieved under well- optimised
reaction conditions. The present protocols should also allow for using substituted
aldehydes (Fig 1B, R≠H) in reactions with mixed tertiary-primary phosphines, likely to
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give diastereomeric product mixtures.15 The possibility of the separation of their borane
protected analogs by chromatographic methods followed by facile deprotection may
lead to a rich ligand chemistry. Research in this direction as well as complexation to
transition metals is currently underway.
Acknowledgement
We thank the European Union (Marie Curie ITN SusPhos, Grant Agreement No.
317404) for financial support.
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10 Lithium cleavage: (a) Wittenberg, D.; Gilman, H. J. Org. Chem. 1958, 23, 1063-1064; Michael addition
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Buchholz, J.; Vidal-Ferran, A. Organometallics 2014, 33, 2960-2963
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Moiseev, D. V.; James, B. R.; Gushchin, A. V. Russ. J. Gen. Chem. 2013, 83, 252-259.
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Figure 1
Scheme 1. Synthesis of the tertiary-primary diphosphine starting material.
Scheme Error! Main Document Only.. Borane protection and deprotection of hydroxymethyl- bearing diphosphine 2.
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Table 1. Formylation of tertiary-primary diphosphine 1.
Entry Formaldehyde
source
Solvent
T
time
1 h
1.5 h
2 h
Conv.
75%
# of product
species
1
2
3
4
PFA (10 equiv.)
PFA (10 equiv.)
Formalin (5 equiv.) EtOH
Formalin (5 equiv.) Et2O
THF
PhCH3
66 oC
1
≥3
1
65 oC
>99%
>99%
>99%
rt
rt
4 h
≥3
10
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