Water-soluble diphosphadiazacyclooctanes as ligands for aqueous organometallic catalysis

Article abstract of DOI:10.1016/j.catcom.2012.09.019

Two new water-soluble diphosphacyclooctanes been synthesized and characterized by NMR and surface tension measurements. Both phosphanes proved to coordinate rhodium in a very selective way as well-defined bidentates were obtained. When used in Rh-catalyzed hydroformylation of terminal alkenes, both ligands positively impacted the reaction chemoselectivity.

Full text of DOI:10.1016/j.catcom.2012.09.019

Catalysis Communications 29 (2012) 77–81
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Water-soluble diphosphadiazacyclooctanes as ligands for aqueous
organometallic catalysis
Jérôme Boulanger a, Hervé Bricout a, Sébastien Tilloy a, Aziz Fihri b, Christophe Len c,
a
Frédéric Hapiot a, , Eric Monflier
⁎
a
Université Lille Nord de France, CNRS UMR 8181, Unité de Catalyse et de Chimie du Solide, UCCS, UArtois, Faculté Jean Perrin, rue Jean Souvraz, SP18, F-62307 Lens Cedex, France
KAUST Catalysis Center (KCC), King Abdullah University of Science and Technology Thuwal 23955, Kingdom of Saudi Arabia
Transformations Intégrées de la Matière Renouvelable - EA 4297 UTC/ESCOM, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, BP 20529,
b
c
rue Personne de Roberval, F-60205 Compiègne cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 July 2012
Received in revised form 14 September 2012
Accepted 14 September 2012
Available online 23 September 2012
Two new water-soluble diphosphacyclooctanes been synthesized and characterized by NMR and surface
tension measurements. Both phosphanes proved to coordinate rhodium in a very selective way as well-defined
bidentates were obtained. When used in Rh-catalyzed hydroformylation of terminal alkenes, both ligands posi-
tively impacted the reaction chemoselectivity.
© 2012 Elsevier B.V. All rights reserved.
Keywords:
Water soluble phosphane
Aqueous catalysis
Hydroformylation
1. Introduction
ofa1,5-diphenyl-3,7-dicyclohexyl-1,5-diaza-3,7-diphosphacyclooctane
ligand which proved to be effective in a Pd-catalyzed Suzuki-Miyaura
Since the 1970's and the synthesis by E. Kuntz of the benchmark
TPPTS ligand, the design of innovative and efficient water-soluble
ligands for aqueous organometallic catalysis has always been a challenge
[1]. The main role of water-soluble ligands is to stabilize a catalyst into the
aqueous phase of a biphasic reaction which results in many benefits [2].
First, the organic products and water-soluble ligand-stabilized catalysts
could be easily separated and recovered upon completion of the reaction
by simple decantation. Second, the catalytic system could be recycled
giving this method a considerable advantage over homogeneous process-
es. Third, even if alternatives have been developed in other media such as
fluorous solvents [3], supercritical CO2 [4,5] and ionic liquids [6], water
remained the best eco-friendly solvent because it is cheap, available in
large quantities, non-toxic and non-flammable, to mention only some
the main features. Most commonly, the synthesis of water-soluble ligands
consists in grafting water-solubilizing groups to known hydrophobic
ligands. In this respect, suitable ionic substituents (sulfonate, carboxyl-
ate, phosphonate, or ammonium) or nonionic hydrophilic substituents
(polyols, carbohydrates, and polyethers) can be used [7–14]. Many
water-soluble mono- and polydentate ligands have thus emerged
among which phosphanes are the most widely used in catalytic pro-
cesses. They have been used in various aqueous organometallic reac-
tions, the most studied being hydrogenation, hydroformylation and
cross-coupling reactions [2]. Recently, one of us published the synthesis
cross-coupling reaction [15]. However, the poor water-solubility of the
ligand limited its application in aqueous organometallic catalysis and
prompted us to develop its water-soluble version. In this context, the
sulfonated ligands 1 and 2 (Scheme 1) have been synthesized and
their catalytic performance has been evaluated in a Rh-catalyzed
hydroformylation of terminal alkenes.
2. Experimental
2.1. General
Organic compounds were purchased from Aldrich Chemicals in their
highest purity and used without further purification. All liquid reagents
were degassed by bubbling nitrogen for 15 min before each use or by
two freeze-pump-thaw cycles before use. Distilled deionized water was
used in all experiments. All reactions and workup procedures were
performed under an inert atmosphere using conventional vacuum-line
and glasswork techniques.
2.2. Mass spectrometry
High-resolution electrospray mass spectra (ESI-HRMS) in the pos-
itive ion mode were obtained on a Q-TOF Ultima Global hybrid quad-
rupole time-of-flight instrument (Waters-Micromass), equipped with
a pneumatically assisted electrospray (Z-spray) ionization source and
an additional sprayer (Lock Spray) for the reference compound. The
⁎
Corresponding author. Tel.: +33 3 2179 1773; fax: +33 3 2179 1755.
E-mail address: frederic.hapiot@univ-artois.fr (F. Hapiot).
1566-7367/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2012.09.019

78
J. Boulanger et al. / Catalysis Communications 29 (2012) 77–81
which yielded a similar white product (4.8 g, 7.2 mmol, 87%). The NMR
analysis of phosphanes 1 and 2 is detailed in Supporting Information.
2.5. Determination of the phosphane basicity
Phosphane selenides were synthesized by refluxing an excess of
selenium (10 eq.) with the phosphane (25 mg) in absolute ethanol
(1.5 mL) under nitrogen for 15 h [16]. The resulting mixture was
directly analyzed by 31P{1H} NMR without any purification. In all
cases, NMR spectra exhibit the presence of phosphane selenides
which are characterized by a singlet with two satellites due to only
7.6% of active selenium isotope (77Se) in NMR spectroscopy.
2.6. Surface tension measurements
The surface tension measurements were performed using a KSV
Instruments digital tensiometer (Sigma 70) with a platinum plate.
The precision of the force transducer of the surface tension apparatus
was 0.1 mN m−1. The experiments were performed at 293 K 0.5
controlled by a thermostated bath Lauda (RC6 CS).
Scheme 1. Water-soluble diphosphadiazacyclooctanes derivatives 1 and 2.
purified compounds were dissolved in methanol (0.01 mg/mL) and
the solutions were directly introduced (5 mL/min) through an inte-
grated syringe pump into the electrospray source. The source and
desolvation temperatures were 80 and 150 °C, respectively.
2.7. Typical procedure for the Rh-catalyzed hydroformylation of terminal
alkenes
In a typical experiment, Rh(acac)(CO)2 (0.04 mmol) and the water-
soluble ligand (0.21 mmol) were dissolved in 11.5 mL of water. The
resulting aqueous phase and the olefin (20.35 mmol) were charged
into the 50 mL reactor, which was heated at the desired temperature.
The mixture was stirred at 1500 rpm and the autoclave was pressurized
with 50 atm of CO/H2 (1:1) from a gas reservoir connected to the reac-
tor through a high-pressure regulator valve allowing to keep constant
the pressure in the reactor throughout the whole reaction. Once the
reaction was complete, the organic phase was recovered by decanta-
tion. Gas chromatographic analyses of the organic phase were carried
out on a Shimadzu GC-17 A gas chromatograph equipped with a polydi-
methylsiloxane capillary column (30 m×0.32 mm) and a flame ioniza-
tion detector (GC:FID).
2.3. NMR measurements
NMR spectra were recorded at 25 °C on a Bruker DRX300 spectrom-
eter operating at 300 MHz for 1H nuclei, 75.5 MHz for 13C nuclei and
121.5 MHz for 31P nuclei. 31P{1H} NMR spectra were recorded with an
external reference (85% H3PO4). D2O (99.92% isotopic purity) was pur-
chased from Euriso-Top.
2.4. Phosphanes synthesis
A Schlenk flask was charged with cyclohexylphosphine (10% in
hexane, 14.6 mL, 8.3 mmol), degassed aqueous formaldehyde (37%,
1.92 mL, 25.8 mmol) and distillated acetonitrile (25 mL). After 2 h
stirring at room temperature, the solvents were removed under
vacuum and the resulting oil was combined with sodium 4-
aminobenzenesulfonate (1.62 g, 8.3 mmol) in degassed ethanol
(20 mL) and was refluxed overnight. The resulting suspension
was cooled to room temperature. The precipitate was filtered
and washed with copious dry ethanol and vacuum dried to
yield phosphane 1 as a white powder (4.6 g, 6.86 mmol, 83%).
A similar procedure was used to synthesize phosphane 2 except
for the use of sodium 3-aminobenzenesulfonate (1.62 g, 8.3 mmol),
3. Results and discussion
3.1. Synthesis of the water-soluble diphosphadiazacyclooctane derivatives
The synthesis of phosphanes 1 and 2 has been carried out as fol-
lows. Once cyclohexylphosphane and aqueous formaldehyde have
been mixed to form the dihydroxymethylphosphane intermediate,
reaction with sodium anilinesulfonates substituted in meta- or para-
position led to the expected diphosphadiazacyclooctane derivatives
Scheme 2. Synthesis of diphosphanes 1 and 2.

J. Boulanger et al. / Catalysis Communications 29 (2012) 77–81
79
(Scheme 2). The synthesis of these ligands is quite straightforward
with high reaction yields (80–90%) and the water solubility of these
phosphanes (about 10 mM at 25 °C) is high enough to make them
practically applicable in aqueous catalysis.
Mass spectrometry analyses confirmed the purity of ligands 1 and
2 (ESI). The NMR analyses of the diphosphanes revealed the magnetic
inequivalence of the methylene protons located between the nitrogen
and the phosphorus atoms. Doublets of doublets were detected char-
acteristic of both a 2J coupling constant between methylene protons
2
(2JH,H =15.4 Hz and JH,H =15.3 Hz for 1 and 2, respectively) and a
2J coupling constant connecting the methylene protons and the phos-
Scheme 3. Chair–chair conformation of diphosphanes 1 and 2.
2
phorus atoms (2JH,P=5.9 Hz and JH,P =5.7 Hz for 1 and 2, respec-
tively). These NMR data suggest that the phosphanes adopted a
chair–chair conformation in which both phosphorus atoms displayed
their electron lone pair on the same side of the molecule (Scheme 3).
A κ2-P,P coordination mode onto a metal atom is then conceivable.
mN.m-1
3.2. Phosphane basicity
70
The 1JP–Se first order phosphorous selenium coupling constants of the
Se=1 and Se=2 selenides are 700 and 720 Hz, respectively. The lower
1JP–Se values obtained for Se=1 and Se=2 indicate that 1 and 2 are
more electron rich and thus more basic than TPPTS (1JP–Se=757 Hz).
The results were coherent with the trialkyl nature of the phosphorus
atoms in 1 and 2 by comparison with TPPTS [16].
65
60
55
: 1
: 2
3.3. Tensiometric measurements
Ligands 1 and 2 have been characterized by surface tension measure-
ments in water. Their ability to modify the air–water interface clearly
appeared when increasing their concentration. A regular decrease in
surface tension γ for each diphosphane was indicative of an interfacial
adsorption in the 1–10 mM concentration range. 2 appeared to be
more surface active than 1 (Fig. 1). Note that no critical micellar concen-
tration could be observed in the studied concentration range. In fact, 1
50
0.1
1.0
10.0 mM
Fig. 1. Tensiometric properties of diphosphanes 1 and 2 as a function of their concen-
tration in water at room temperature.
Fig. 2. 31P{1H} NMR spectrum of a 6 mM solution of [Rh(COD)(2)+, BF4−] in a D2O/EtOH (50/50) mixture.

80
J. Boulanger et al. / Catalysis Communications 29 (2012) 77–81
(i)
(h)
(g)
(f)
(e)
(d)
(c)
(b)
(a)
Fig. 3. 31P{1H} NMR spectra (121.5 MHz, DMSO-D6) of a mixture of [Rh(COD)2+, BF4−] (12 mM) and 2. (a) 1 eq. of 2 (12 mM) after 10 min at 20 °C (recorded at 20 °C), (b) 1.5 eq. of
2 (18 mM) after 10 min at 20 °C (recorded at 20 °C), (c) 1.5 eq. of 2 (18 mM) after 10 min at 60 °C (recorded at 60 °C), (d) 1.5 eq. of 2 (18 mM) after 30 min at 60 °C (recorded at
60 °C), (e) 2 eq. of 2 (24 mM) after 10 min at 20 °C (recorded at 20 °C), (f) 2 eq. of 2 (24 mM) after 10 min at 60 °C (recorded at 60 °C), (g) 2 eq. of 2 (24 mM) after 20 min at
60 °C (recorded at 60 °C), (h) 2 eq. of 2 (24 mM) after 30 min at 60 °C (recorded at 60 °C), i) 2 eq. of 2 (24 mM) after 30 min at 60 °C (recorded at 20 °C).
and 2 could be considered hydrotropic. Over about 10 mM for 1 and
8 mM for 2, no data could be collected because of solubility limitations.
3.5. Rh-catalyzed hydroformylation of terminal alkenes
The catalytic performances of 1 and 2 were evaluated in Rh-catalyzed
hydroformylation of two different alkenes, namely methyl 4-pentenoate
(3) and acetoxystyrene (4). Rh(CO)2(acac) (acac=acetylacetonate) was
used as catalytic precursor under 50 bar CO/H2. The first catalytic runs
have been carried out using 3, a partially water-soluble substrate able to
react directly in the aqueous bulk. Table 1 showed that the conversion
was very dependent upon the ligand proportion.
3.4. Coordination properties
NMR experiments realized in a D2O/EtOH mixture (50/50) showed
that mixing the Rh(COD)2BF4 cationic precursor and 1 or 2 in stoi-
chiometric proportion gave the expected [Rh(COD)(1)+, BF4−] and
[Rh(COD)(2)+, BF4−] complexes. Fig. 2 is illustrative of the 31P{1H} spec-
trum obtained for [Rh(COD)(2)+, BF4−]. The well-defined doublet
(1JRh-P=132.5 Hz) is characteristic of two phosphorus in a symmetrical
environment and coordinated to the rhodium center in a κ2-P,P coordi-
nation mode (Fig. 2). No other Rh-complexes could be detected infor-
mative of the very selective coordination mode of the ligand onto the
metal.
Using 1 eq. ligand 1 at 80 °C (Table 1, run 1), a total conversion was
reached within 150 min along with an excellent 99% chemoselectivity
Table 1
Rh-catalyzed hydroformylation of methyl 4-pentenoate (3) and acetoxystyrene (4).
Run Substrate Phosphane L/
Temp. Conversion Aldehydes
l/b
Rh (°C)
(%)
selectivity (%)
An additional experiment has been carried out in a D2O/EtOH mix-
ture (50/50) with Rh(COD)2BF4 as a cationic precursor and 2 equiv. 2.
In these conditions, a new Rh-species could be detected. The 31P NMR
1
2
3
4
5
6
7
8
9
10
3
3
3
3
3
3
3
4
4
4
1
1
1
2
2
2
1
2
2
1
2
2
1
1
1
1
80
80
100
80
80
100
80
80
80
80
100
8
99
90
95
95
98
96
98
98
98
90
1.1
1.7
1.7
1.2
0.9
0.9
1.2
0.5
0.3
0.07
23
95
12
14
99
83
78
99
signal was upfield shifted (5.54 ppm vs. 11.89 ppm for [Rh(COD)(2)+
,
BF4−] and revealed a more electron-rich metallic center. Here again,
the doublet was characteristic of phosphorus atoms in a symmetrical
DPPPTS
1
2
1
environment with a JRh-P coupling constant of 120.8 Hz and could be
attributed to the planar [Rh(2)2+, BF4−] complex (ESI). The proportion
of the latter could be varied depending on the ligand amount as
depicted in Fig. 3. 100% [Rh(2)2+, BF4−] could be obtained after heating
the solution at 60 °C for 30 min in the presence of 2 eq. of 2.
DPPPTS
Conditions: n(Rh(CO)2(acac))=3.88 μmol (1 mg), substrate (1.94 mmol), 12 mL water,
reaction time=150 min, 50 bar CO/H2, substrate/Rh=500.

J. Boulanger et al. / Catalysis Communications 29 (2012) 77–81
81
in aldehydes and a poor regioselectivity (l/b=1.1). Thus, almost no
isomerization of the C_C double bond occurred during the catalytic
process, thus highlighting the selective ability of the catalyst to orient
the reaction towards the hydroformylation process. However, the low
l/b ratio clearly indicated that no preference was given to one or the
other alkenyl carbon for them to be functionalized by a formyl group.
Increasing the amount of 1 at 80 °C (Table 1, run 2) led to a huge
decrease in the conversion (from 100% to 8% within 150 min). As clearly
established above (see Section 3.4), a high-coordinated rhodium spe-
cies was probably formed with negative impact on the substrate com-
plexation. The significant drop in conversion was accompanied by a
slight decrease in chemoselectivity (90% aldehydes) and an increase
in regioselectivity (l/b=1.7). Increasing the temperature from 80 to
100 °C did not counterbalance the ligand effect as 23% conversion was
only reached within 150 min (Table 1, run 3). In that case, the aldehyde
proportion was slightly higher (95.0%) and the l/b ratio remained
constant (1.7). A similar trend was observed for 2 in terms of catalytic
activity. Thus, from 95% with 1 eq. 2 at 80 °C (Table 1, run 4), the con-
version dropped to 12 and 14% at 80 and 100 °C, respectively. While
the chemoselectivity was hardly impacted by variation of proportions
in 2 (in the range 95–98% aldehydes), the regioselectivity suffered
from an excess 2 in solution as a very low 0.9 l/b ratio was measured
using 2 eq. 2 at any temperature (Table 1, runs 5 and 6). When compar-
ing 1 and 2, no significant difference in catalytic performances could be
noticed. Thus, using a linear terminal alkene as substrate, the para- or
meta-position of the sulfonate groups had no real influence on the coor-
dination sphere. This conclusion was coherent with the geometry of the
Rh-complexes when coordinated by 1 or 2. Indeed, a structural study
carried out on non-sulfonated analogues of 1 and 2 showed the phenyl
groups to be far from the metallic center [17]. Consequently, the steric
hindrance around the metal was not high enough to discriminate the
two C_C carbons. To complete this series of experiments, the catalytic
behavior of 1 and 2 has been compared to a structurally close water-
soluble ligand, namely the well-known DPPPTS (tetra-sulfonated 1,3-
bis(diphenylphosphino)propane). DPPPTS has been chosen as its two
phosphorus atoms are distant from each other by four covalent bonds,
as observed for 1 and 2. Ligands 1 or 2 appeared to be as effective as
DPPPTS, either in terms of conversion or selectivities (run 7), thus
highlighting their bidentate nature during the course of the reaction.
The Rh-catalyzed hydroformylation has been widened to
acetoxystyrene (Table 1, runs 7 and 8). 83% and 78% of substrate were
converted at 80 °C under 50 bar CO/H2 within 150 min using 1 and 2,
respectively (Table 1, run 1 and 2). As observed for 3, the chemose-
lectivity was high (98% aldehydes). Contrary to what was usually
observed for terminal alkenes, it is well known that Rh-catalyzed
hydroformylation of styrene derivatives mainly led to branched alde-
hydes because of the formation, during the catalytic cycle, of a pseudo
π-allyl intermediate. In this context, it appeared that the Rh-catalyst
stabilized by 1 equiv 2 was more regioselective than that stabilized by
1 as higher proportions of branched aldehydes were formed (76% vs.
65%, respectively). As observed above for 3, conversion of 4 was
performed as efficiently using 1 or 2 than using DPPPTS, even if the
selectivity in branched aldehyde was somewhat lower with 1 or 2.
4. Conclusion
In this study, two new water-soluble diphosphadiazacyclooctane
derivatives have been synthesized using a straightforward two-step syn-
thetic procedure. They displayed a κ2-P,P coordination mode on rhodium
complexes. We demonstrated their potential in rhodium-catalyzed
hydroformylation of two terminal alkenes. The conversion proved to be
very dependent upon the phosphane/Rh ratio. A stoichiometric propor-
tion was optimized to yield high conversion. The high chemoselectivities
attainable in hydroformylation of terminal alkene derivatives con-
stitute without doubt one of the main advantages of these new
diphosphanes as water-soluble ligands. Extension of the use of
water-soluble diphosphadiazacyclooctane derivatives to other cata-
lytic reactions is currently on-going.
Acknowledgments
This work was supported by the Centre National de la Recherche
Scientifique (CNRS).
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://
dx.doi.org/10.1016/j.catcom.2012.09.019.
References
[1] E.G. Kuntz, ChemTech (1987) 570.
[2] K.H. Shaughnessy, Chemical Reviews 109 (2009) 643.
[3] D.P. Curran, Angewandte Chemie International Edition 37 (1998) 1174.
[4] W. Leitner, Accounts of Chemistry Research 35 (2002) 746.
[5] D. Prajapati, M. Gohain, Tetrahedron 60 (2004) 815.
[6] M. Haumann, A. Riisager, Chemical Reviews 108 (2008) 1474.
[7] V. Pârvulescu, C. Hardacre, Chemical Reviews 107 (2007) 2615.
[8] C. Machut, J. Patrigeon, S. Tilloy, H. Bricout, F. Hapiot, E. Monflier, Angewandte
Chemie International Edition 46 (2007) 3040.
[9] H. Fu, M. Li, J. Chen, R. Zhang, W. Jiang, M. Yuan, H. Chen, X. Li, Journal of Molec-
ular Catalysis A: Chemistry 292 (2008) 21.
[10] M. Ferreira, H. Bricout, A. Sayede, A. Ponchel, S. Fourmentin, S. Tilloy, E. Monflier,
Advanced Synthesis and Catalysis 350 (2008) 609.
[11] S. Tilloy, F. Hapiot, D. Landy, S. Fourmentin, V. Michelet, J.P. Genêt, E. Monflier, Ad-
vanced Synthesis and Catalysis 348 (2006) 1547.
[12] C. Machut-Binkowski, F.X. Legrand, N. Azaroual, S. Tilloy, E. Monflier, Chemistry–
A European Journal (2010) 10195.
[13] H. Bricout, E. Banaszak, C. Len, F. Hapiot, E. Monflier, Chemical Communications
46 (2010) 7813.
[14] D. Ngan Tran, F.X. Legrand, S. Menuel, H. Bricout, S. Tilloy, E. Monflier, Chemical
Communications 48 (2012) 753.
[15] A. Fihri, D. Luart, C. Len, A. Solhy, C. Chevrin, V. Polshettiwar, Dalton Transactions
40 (2011) 3116.
[16] M. Ferreria, H. Bricout, A. Sayede, F. Hapiot, S. Tilloy, E. Monflier, ChemSusChem 1
(2008) 631.
[17] S. Otto, A. Ionescu, A. Roodt, Journal of Organometallic Chemistry 690 (2005)
4337.