Modular diphosphine ligands based on bisphenol A backbones

Article abstract of DOI:10.1016/S0040-4039(03)00948-1

A straightforward two-step synthesis is used to obtain new phosphorus-containing ligands based on readily available bisphenol A type backbones. Five diphosphine ligands have been prepared in good yields. An X-ray crystallographic study is presented for li

Full text of DOI:10.1016/S0040-4039(03)00948-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4389–4392
Modular diphosphine ligands based on bisphenol A backbones
Jarl Ivar van der Vlugt,a Josep M. Bonet,a Allison M. Mills,b Anthony L. Spekb and Dieter Vogta,*
aSchuit Institute of Catalysis, Laboratory of Homogeneous Catalysis, Eindhoven University of Technology, PO Box 513,
5600 MB Eindhoven, The Netherlands
bDepartment of Crystal and Structural Chemistry, Padualaan 8, University of Utrecht, The Netherlands
Received 19 November 2002; revised 3 April 2003; accepted 10 April 2003
Abstract—A straightforward two-step synthesis is used to obtain new phosphorus-containing ligands based on readily available
bisphenol A type backbones. Five diphosphine ligands have been prepared in good yields. An X-ray crystallographic study is
presented for ligand 5. Preliminary results on rhodium-catalyzed hydroformylation exemplify the use of these ligands for
homogeneous catalysis. © 2003 Elsevier Science Ltd. All rights reserved.
Homogeneous catalysis has proven to be a very power-
ful tool for the synthesis of various intermediates and
fine chemicals.1 The success of homogeneous transition
metal catalysts strongly depends on the ligands used. A
large number of the ligands applied in such reactions
are based on phosphorus donors and backbones such
as biphenyl,2 xanthene3 or norbornene.4 Frequently the
starting materials are either expensive or not commer-
cially available. In addition, structural variations and
exchange of functional groups is not always easy in
these systems while nowadays the aim is to create
modular, highly variable ligand classes made from read-
ily available materials.
ligand classes. A broad variety of these bisphenols are
commercially available at low cost since they are major
components in epoxy resins.5 Generic structures are
easily accessible by simple acid-catalyzed condensation
of a ketone with two molecules of a phenol. Here we
report the first examples of a new class of ligands based
on bisphenol A type backbones. Their application in
the rhodium-catalyzed hydroformylation of 1-octene
exemplifies their use and potential for homogeneously
catalyzed reactions.
Based on three derivatives of bisphenol A, we applied a
simple, straightforward two-step synthetic route
(Scheme 1). The approach was to use protected pheno-
lic OH-groups as directing groups for the selective
ortho-lithiation of both phenyl rings followed by reac-
We have selected bisphenol A and its derivatives as
starting compounds for the development of modular
Scheme 1. Synthetic methodology to generic ligands 1–4. Reagents and conditions: (i) MeI, K2CO3, acetone, reflux 16 h, 85%; (ii)
n-BuLi, TMEDA, −15°C, ether, 1 h, then SiCl2Me2, 72%; (iii) n-BuLi, TMEDA, −15°C, ether, 16 h, then ClPPh2, hexanes, 0°C,
16 h, 60%.
Keywords: bisphenol A; terphenyl; modular backbone; diphosphine ligand; homogeneous catalysis; rhodium.
* Corresponding author. Tel.: +31 40 2472483; fax: +31 40 2455054; e-mail: d.vogt@tue.nl
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00948-1

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J. I. 6an der Vlugt et al. / Tetrahedron Letters 44 (2003) 4389–4392
tion with a suitable phosphorus compound, in this case
ClPPh2. In this manner a wide range of phosphorus
containing ligands is accessible. Using this method we
obtained ligands 1–3 based on bisphenol A derived
backbones.6
particular reaction to 85% using Na2CO3 as the base.
Simple workup by filtration and evaporation of the
solvent followed by washing of the crude product with
methanol afforded the pure compounds in overall yields
of 40–50%.
This modular approach allows for variation in rigidity,
steric bulk and electronic properties of the ligands.
Introduction of other P-containing groups is also on
option, leading to, for instance, phosphonites.7 Taking
advantage of the selective ortho-lithiation approach,
and starting from 4-bromoanisole we also synthesized a
silicon-bridged bisphenol ligand 4 as well as a ligand
based on a terphenyl backbone, ligand 5, which we
have named Terphos (Scheme 2). In this latter case, the
appropriate backbone, compound II, which was
obtained in two steps via palladium-catalyzed Suzuki-
coupling using 1,2-dibromobenzene, has been reported
by Blake et al., with a yield of only 66% when using
Ba(OH)2 as the base.8 We improved the yield of this
Ligand 5 could be crystallized from hot acetonitrile
which gave crystals suitable for X-ray analysis.9 The
molecular structure of 5 is depicted in Figure 1 together
with selected bond lengths and angles. The terphenyl
backbone has an approximately C2 symmetry, the two
peripheral aromatic rings being tilted at angles of
48.22(9) and 49.70(9)° with respect to the central ring.
Because of the rotational freedom of the peripheral aryl
rings of the terphenyl backbone, the diphenylphosphine
groups are not constrained to any particular mutual
orientation. The dihedral angles between the aromatic
rings in the backbone are calculated to be 115.8 and
144.4° giving rise to the different spatial arrangements
of the phosphorus atoms.
Scheme 2. Synthetic-route to ligand 5. Reagents and conditions: (i) 1,2-dibromobenzene, Na2CO3, Pd(PPh3)4, DME, H2O, D, 16
h, 85%; (ii) n-BuLi, TMEDA, −40°C, Et2O, 16 h; (iii) ClPPh2, hexanes, 0°C, 16 h, 60%.
Figure 1. Ortep drawing of the crystal structure of ligand 5 (Terphos). Hydrogen atoms are omitted for clarity. Thermal ellipsoids
,
are drawn at the 50% probability level. Selected bond lengths (A): P1ꢀC3 1.8322(19), P2ꢀC9 1.8362(19), O1ꢀC1 1.431(3), O2ꢀC2
1.433(3). Selected bond angles (°): C3ꢀP1ꢀC21 101.85(9), C3ꢀP1ꢀC27 105.36(8), C21ꢀP1ꢀC27 101.13(9), C9ꢀP2ꢀC33 101.81(9),
C9ꢀP2ꢀC39 104.56(9), C33ꢀP2ꢀC39 100.62(9), C1ꢀO1ꢀC4 117.83(18), C2ꢀO2ꢀC10 116.34(16), C7ꢀC15ꢀC16 124.69(16), C13ꢀC16ꢀC15
125.16(16).

J. I. 6an der Vlugt et al. / Tetrahedron Letters 44 (2003) 4389–4392
4391
Our approach is not comparable to earlier work on the
synthesis of ligands based on bisphenol A type back-
bones. To the best of our knowledge there are only two
reports so far in the literature using bisphenol A as a
building block for phosphorus ligands; however, they
deal with the functionalization of the phenolic OH-
groups10 and the formation of phosphite-bridged
macrocycles.11
of the substrate occurred. Furthermore, the catalytic
system based on Terphos (ligand 5) shows the typical
behavior expected for diphosphine ligands concerning
the influence of temperature, pressure and CO/H2 ratio
(entries 6–9).
In conclusion, we have described a two-step synthetic
route to a new and modular class of phosphorus con-
taining ligands, based on bisphenol A derived skeletons.
As a first introduction four diphosphine ligands were
prepared in good yields. Based on the same methodol-
ogy, we used a new terphenyl backbone to obtain a
fifth ligand, Terphos. For this ligand the X-ray struc-
ture is presented. In the rhodium-catalyzed hydro-
formylation of 1-octene high activities were obtained,
especially for ligand 5. For this new class of ligands we
are currently investigating the coordination with vari-
ous transition metals and the activity in other catalytic
reactions. The family will be extended by introduction
of other phosphorus containing groups.
To illustrate the applicability of the new phosphorus
ligands in homogeneous catalysis, we chose the
rhodium catalyzed hydroformylation of 1-octene as an
example (Scheme 3). The catalysis was carried out
under typical hydroformylation conditions, 20 bar of
syngas (CO/H2 1:1) and a temperature of 80°C.
There is a direct influence of the flexibility and steric
crowding of the central-atom in the backbone skeleton
on the activity of the corresponding catalyst. The least
rigid ligand 1 (entry 1, Table 1) gave a TOF of 735 h−1.
The activity was improved to a TOF of 1029 h−1 when
a cyclohexyl-moiety was present in the backbone of
ligand 2 (entry 2) while with ligand 3 the activity
increased further to a TOF of 1418 h−1 (entry 3).
Selectivity for the terminal aldehyde is moderate with a
linear to branched (l/b) ratio of about 3. This is
expected as these ligands are not optimized to obtain a
high regioselectivity, as far as rigidity, bulkiness and
bite-angle are concerned. For ligand 4 (entry 4) the
activity was unexpected since it was thought to resem-
ble ligand 1.
Acknowledgements
This work is financially supported by the National
Research School Combination for Catalysis (NRSCC)
and in part (A.M.M. and A.L.S.) by the Netherlands
Foundation of Chemical Research (SON) with financial
aid from the Netherlands Organisation for Scientific
Research (CW-NWO). J.M.B. thanks the Erasmus pro-
gram of the European Union for a travel grant. OMG
is gratefully acknowledged for providing a stock of
Rh(acac)(CO)2. We like to thank Dr. Ahlers and Dr.
Paciello (BASF AG) and Dr. Rafael Sablong (TU/e)
for valuable scientific discussions.
Ligand 5 turned out to give the highest activity, with a
turnover frequency up to nearly 3500 h−1 which leads to
a conversion of nearly 22% after 15 min (entry 5). No
side reactions such as hydrogenation and isomerization
Scheme 3. Hydroformylation of 1-octene.
Table 1. Hydroformylation of 1-octene catalyzed by [Rh(acac)(CO)2]/1–5a
Entry
Ligand
Time (min)
Temperature (°C)
p (bar)
Conversion (%)b Sel.aldehyde(%)b
l/b ratiob
TOF (h−1 c
)
1
2
3
4
5
6
7
8
9
1
2
3
4
5
5
5
5
5
60
60
60
60
15
60
60
60
60
80
80
80
80
80
80
70
60
60
20
20
20
20
20
30
20
20
20d
18.8
26.8
35.4
31.6
21.8
40.0
20.3
8.3
97.9
99.0
99.2
99.3
98.1
97.6
98.4
98.3
98.9
2.8
2.9
2.7
2.9
3.0
2.9
3.0
3.0
2.4
735
1029
1418
1250
3485
1615
800
325
620
15.8
a Reaction conditions: 1-octene (31.0 mmol), [Rh(acac)(CO)2] (0.39 mM), decane (12.5 mmol), toluene (12.7 mL), 1-octene:Rh=4000:1,
preformation time 1 h, L:Rh=6:1.
b Determined by GC.
c TOF in mol 1-octene·mol Rh−1 h−1 determined by GC.
d p(H2):p(CO)=3:1.

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J. I. 6an der Vlugt et al. / Tetrahedron Letters 44 (2003) 4389–4392
following dimensions: a=9.4589(1) A, b=0110.8619(2)
,
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