Template-induced formation of heterobidentate ligands and their application in the asymmetric hydroformylation of styrene

Article abstract of DOI:10.1039/b609321c

We report the template-induced formation of chelating heterobidentate ligands by the selective self-assembly of two different monodentate ligands on a rigid bis-zinc(ii)-salphen template with two identical binding sites; these templated heterobidentate ligands induce much higher enantioselectivities (up to 72% ee) in the rhodium-catalyzed asymmetric hydroformylation of styrene than any of the corresponding homobidentate ligands or non-templated mixed ligand combinations (up to 13% ee). The Royal Society of Chemistry.

Full text of DOI:10.1039/b609321c

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Template-induced formation of heterobidentate ligands and their
application in the asymmetric hydroformylation of styrene{
Mark Kuil, P. Elsbeth Goudriaan, Piet W. N. M. van Leeuwen and Joost N. H. Reek*
Received (in Cambridge, UK) 30th June 2006, Accepted 3rd August 2006
First published as an Advance Article on the web 15th August 2006
DOI: 10.1039/b609321c
template with two identical binding sites (Fig. 1). These templated
heterobidentate ligands induce much higher enantioselectivities in
the rhodium-catalyzed asymmetric hydroformylation of styrene
than their non-templated analogues.
We report the template-induced formation of chelating hetero-
bidentate ligands by the selective self-assembly of two different
monodentate ligands on a rigid bis-zinc(II)-salphen template
with two identical binding sites; these templated heterobidentate
ligands induce much higher enantioselectivities (up to 72% ee) in
the rhodium-catalyzed asymmetric hydroformylation of styrene
than any of the corresponding homobidentate ligands or non-
templated mixed ligand combinations (up to 13% ee).
The building blocks used in this contribution (1–3, a–h) were all
prepared in a straightforward manner.7 The formation of
bidentate phosphorus ligands takes place in situ by selective
coordination of the nitrogen donor atom of ligand a–h to the zinc
atoms of the bis-Zn-salphen template 3, and the phosphorus donor
atoms are still available for complexation to palladium or
rhodium.8 Titration experiments in toluene monitored by UV-vis
spectroscopy revealed that the bis-Zn-salphen template binds
two ligands a with corresponding binding constants of K1 5 2.4 6
104 M21 and K2 5 1.5 6 104 M21. The formation of templated
homobidentate palladium complexes such as [Pd(CH3)Cl(3(a)2)]
and [Pd(CH3)Cl(3(b)2)] was evidenced by 31P NMR studies.7
Homobidentate and heterobidentate ligands comprise a very
important class of ligands in homogeneous transition metal
catalysis,1 but compared to monodentate ligands2,3 their synthesis
is more tedious. Supramolecular (hetero)bidentate ligands4 do not
suffer from these synthetic disadvantages and therefore represent
an important new class of ligands that is well-suited for
combinatorial approaches. In the supramolecular approach two
monodentate ligands are brought together by a self-assembly
process using non-covalent interactions such as hydrogen bonds or
dynamic metal–ligand interactions. Two monodentate ligands can
be assembled by using ligands with complementary binding
motifs,5 or alternatively a template can be used that contains
binding sites for the assembly of two monodentate ligands.6
Herein, we report the template-induced formation of chelating
heterobidentate ligands by the selective self-assembly of two
different monodentate ligands on a rigid bis-zinc(II)-salphen
Since template 3 contains two identical binding sites, the use of
mixtures of ligands in the presence of the template was expected to
lead to mixtures of complexes, in analogy to the work of Reetz and
of de Vries and Feringa.3 Remarkably, a mixture of c + d in the
presence of the rhodium-precursor [Rh(acac)(CO)2] and the bis-
zinc(II)-salphen template 3 showed exclusive formation of the
templated heterobidentate catalyst assembly [Rh(acac)CO(3(c +
d))]. The corresponding homocombinations were not observed at
all by 31P NMR spectroscopy (Scheme 1).7 In contrast, in the
absence of template, only the two homocombinations
Fig. 1 Schematic representation (left) and molecular modeling picture
(right) of the templated heterobidentate complex [HRh(CO)2(3(a + c))]
(green 5 C, white 5 H, blue 5 N, red 5 O, purple 5 P, purple 5 Rh and
purple 5 Zn).
Van’t Hoff Institute for Molecular Sciences, University of Amsterdam,
Nieuwe Achtergracht 166, 1018 WV Amsterdam, The Netherlands.
E-mail: reek@science.uva.nl; Fax: +31 20 5256422; Tel: +31 20 5256437
{ Electronic supplementary information (ESI) available: Ligand synthesis,
experimental details and additional catalytic results. See DOI: 10.1039/
b609321c
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Chem. Commun., 2006, 4679–4681 | 4679

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Scheme 1 Schematic representation of the selective formation of templated heterobidentate rhodium complexes.
[Rh(acac)CO(c)2] and [Rh(acac)CO(d)2] were formed, and the
heterocombination [Rh(acac)CO(c)(d)] could not be detected at
all.7 Likewise, when the mono-zinc(II)-salphen building block 1
was used, exclusive formation of the homocomplexes was
observed.7
Templated heterobidentate ligands were also formed by other
ligand building blocks, as is clear from the catalysis results. For
example, the bis-zinc(II)-salphen templated heterobidentate ligand
(3(c + a)) provided a rhodium catalyst that gave the product with
high enantioselectivity of 72% ee (entry 12), whereas the non-
templated catalysts based on these ligands (entries 10 and 11)
provide the product almost in racemic form. The combinations of
c/e, c/b, c/f and f/g all gave similar enhanced enantioselectivities in
the presence of the template (entries 15–18).7 As predicted by the
molecular modeling studies, the approach does not work for a
combination of two sterically hindered ligands. For example,
phosphite d and phosphoramidite f provide the product in low ee,
also in the presence of a template (entry 19).9
There are no electronic changes of the metal complexes in going
from the non-templated to the templated state, indicating that the
selective formation of heterobidentate ligated metal complexes
must be sterically driven. Molecular modeling studies at the PM3
level show that the reorganization energy of the metal complexes in
going from the non-templated to the templated state is much
higher for the bulky ligands than for non-bulky ligands. For
example, the energy to reorganize HRh(CO)2(c)2 such that it
can coordinate to the template with the two pyridyl groups is
8.6 kcal/mol, whereas for HRh(CO)2(a)2 and HRh(CO)2(a)(c) this
is 4.9 and 4.7 kcal/mol, respectively.7 This is clearly visible in the
structural changes (Fig. 2) and it suggests that the selective
formation of heterobidentate ligated complexes is disadvantaged if
both ligands are very bulky, which is supported by the catalysis
data (vide infra).
Table 1 Asymmetric Rh-catalyzed hydroformylation of styrenea
The templated heterobidentate ligand assemblies were studied in
the rhodium-catalyzed asymmetric hydroformylation of styrene
(Table 1). Rhodium complexes based on ligand c (entries 1–3) all
showed a low conversion whereas the rhodium complexes based
on ligand d (entries 4–6) all gave full conversion and a low
enantiomeric excess of the product (13%). Surprisingly, the catalyst
based on the templated heterobidentate ligand 3(c + d) gave much
higher ee (55%) at slightly lower conversion (entry 9). Control
experiments using mixed ligand combinations c + d and 1c + 1d
(entries 7 and 8) gave low ee (approximately 10%) and full
conversion, indicating that the template 3 plays a crucial role.
These results are completely in line with the NMR data and
support the formation of the templated heterobidentate (3(c + d))
catalyst assembly under catalytic conditions, which is also the most
selective of the series.
Entry
homocombinations
Ligands
Template
% conv.b
b/lc
% eed
1
2
3
c/c
c/c
c/c
d/d
d/d
d/d
—
1
3
—
1
3
, 1
, 1
, 1
. 99
. 99
. 99
—
—
—
12.2
12.5
13.5
—
—
—
11
11
13
4e
5e
6e
heterocombinations
7
8
9
c/d
c/d
c/d
c/a
c/a
c/a
c/e
c/e
c/e
c/b
c/f
f/g
d/f
d/h
d/h
d/h
—
1
3
—
2
3
—
2
3
3
3
3
3
—
1
3
. 99
. 99
66
33
20
19
28
21
20
12.0
12.3
9.90
10
10
55
0
4
72
0
10
11
12
13
14
15
16
17f
18f
19f
20g
21g
22g
a
8.02
8.40
9.20
7.56
9.26
8.21
3.92
4.20
4.20
6
55
57
61
53
6
3
3
4
12
2.0
1.3
84
97
93
16.0
11.3
12.4
21
5.30
[Rh(acac)(CO)2]
5
1.0 mmol/l in toluene, [phosphorus]
5
5
10 mmol/l, styrene/rhodium 5 1000, pressure 5 20 bar (CO/H2
b
1/1), temperature 5 40 uC. Percentage conversion; the reaction was
stopped after 87 h. Ratio of branched to linear product. In all
c
d
Fig. 2 Preorganization of HRh(CO)2(a)(c) (left) and HRh(CO)2(c)2
(right) adjusting from the non-templated (green) to the templated (yellow)
state.
e
cases the S enantiomer of the product was formed. 16 h. 20 h.
f
g
48 h.
4680 | Chem. Commun., 2006, 4679–4681
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T. P. Clark, C. R. Landis, S. L. Freed, J. Klosin and K. A. Abboud,
J. Am. Chem. Soc., 2005, 127, 5040; (g) A. T. Axtell, C. L. Cobley,
J. Klosin, G. T. Whiteker, A. Zanotti-Gerosa and K. A. Abboud,
Angew. Chem., Int. Ed., 2005, 44, 5834; (h) Y. Yan and X. Zhang, J. Am.
Chem. Soc., 2006, 128, 7198.
2 See for example: (a) C. Claver, E. Fernandez, A. Gillon, K. Heslop,
D. J. Hyett, A. Martorell, A. G. Orpen and P. G. Pringle, Chem.
Commun., 2000, 961; (b) M. T. Reetz and G. Mehler, Angew. Chem.,
Int. Ed., 2000, 39, 3889; (c) M. van den Berg, A. J. Minnaard,
E. P. Schudde, J. van Esch, A. H. M. de Vries, J. G. de Vries and
B. L. Feringa, J. Am. Chem. Soc., 2000, 122, 11539.
3 (a) M. T. Reetz, T. Sell, A. Meiswinkel and G. Mehler, Angew. Chem.,
Int. Ed., 2003, 42, 790; (b) D. Pen˜a, A. J. Minnaard, J. A. F. Boogers,
A. H. M. de Vries, J. G. de Vries and B. L. Feringa, Org. Biomol.
Chem., 2003, 1, 1087; (c) M. T. Reetz and X. Li, Angew. Chem., Int. Ed.,
2005, 44, 2959; (d) M. T. Reetz and X. Li, Angew. Chem., Int. Ed., 2005,
44, 2962; (e) R. Hoen, J. A. F. Boogers, H. Bensmann, A. J. Minnaard,
A. Meetsma, T. D. Tiemersma-Wegman, A. H. M. de Vries, J. G. de
Vries and B. L. Feringa, Angew. Chem., Int. Ed., 2005, 44, 4209; (f)
M. T. Reetz, Y. Fu and A. Meiswinkel, Angew. Chem., Int. Ed., 2006,
45, 1412.
Remarkably, all ligands that gave high ee had at least one ligand
with a R2P–N(H)-R1 moiety. Control experiments with rhodium
complexes based on a methylated phosphoramidite ligand h and a
bulky phosphite ligand d (ee-isomer)10 all gave low ee (templated
or not), suggesting a non-innocent role for the N–H moiety
(entries 20–22).7
To get more information on the structure of the complex
formed under hydroformylation conditions we performed high-
pressure IR and NMR spectroscopy studies. High-pressure IR
data indicate the formation of the heteroligated HRh(CO)2(3(c +
d)) complex in which both phosphorus donor atoms coordinate in
the equatorial plane of the trigonal bipyramidal rhodium
complex.7 The IR spectrum shows two absorption bands for the
carbonyl ligands at 2056 and 2008 cm21, typical of an ee isomer.11
In contrast, the non-templated mixed ligand combination showed
the presence of various rhodium-complexes in the reaction
mixture.7 Additional support for the formation of the ee-isomer
of HRh(CO)2(3(c + d)) complex was obtained from high-pressure
NMR data7 showing coupling constants of J{Rh–Pc) 5 216 Hz
and J{Rh–Pd) 5 253 Hz, typical of a complex containing an
equatorial amidite12 and an equatorial phosphite13 respectively. It
was previously demonstrated that the coordination of the ligands
in an ee disposition is an important prerequisite for the formation
of (enantio)selective Rh-catalysts.14 These templated heterobiden-
tate ligands coordinating in a ee-fashion are a promising class of
ligands through variation of the substituents in the equatorial
plane.
4 For reviews see: (a) M. J. Wilkinson, P. W. N. M. van Leeuwen and
J. N. H. Reek, Org. Biomol. Chem., 2005, 3, 2371; (b) B. Breit, Angew.
Chem., Int. Ed., 2005, 44, 6816; (c) A. J. Sandee and J. N. H. Reek,
Dalton Trans., 2006, 3385.
5 (a) B. Breit and W. Seiche, J. Am. Chem. Soc., 2003, 125, 6608; (b)
B. Breit and W. Seiche, Angew. Chem., Int. Ed., 2005, 44, 1640; (c)
J. M. Takacs, D. S. Reddy, S. A. Moteki, D. Wiu and H. Palencia,
J. Am. Chem. Soc., 2004, 126, 4494; (d) V. F. Slagt, M. Ro¨der,
P. C. J. Kamer, P. W. N. M. van Leeuwen and J. N. H. Reek, J. Am.
Chem. Soc., 2004, 126, 4056; (e) J. N. H. Reek, M. Ro¨der,
P. E. Goudriaan, P. C. J. Kamer, P. W. N. M. van Leeuwen and
V. F. Slagt, J. Organomet. Chem., 2005, 690, 4505; (f) F. Chevallier and
B. Breit, Angew. Chem., Int. Ed., 2006, 45, 1599; (g) X.-B. Jiang,
L. Lefort, P. E. Goudriaan, A. H. M. de Vries, P. W. N. M. van
Leeuwen, J. G. de Vries and J. N. H. Reek, Angew. Chem., Int. Ed.,
2006, 45, 1223; (h) M. Weis, C. Waloch, W. Seiche and B. Breit, J. Am.
Chem. Soc., 2006, 128, 4188.
In summary, we have shown, for the first time, a template-
induced selective formation of a chelating heterobidentate ligand.
This heterobidentate ligand is formed by self-assembly of two
different monodentate ligands on a bis-zinc(II)-salphen template
molecule that contains two identical binding sites. These templated
heterobidentate ligands gave rise to catalysts that provided much
higher enantioselectivities (up to 72% ee) in the asymmetric
rhodium catalyzed hydroformylation of styrene than any of the
corresponding homobidentate ligands or non-templated mixed
ligand combinations (up to 13% ee). With the experiments
described herein we have introduced a new method for the easy
preparation of heterobidentate ligands that can be used for
asymmetric catalysis. We are currently exploring this strategy in a
combinatorial fashion for various asymmetric transformations.
We gratefully acknowledge NWO-CW for financial support.
6 (a) V. F. Slagt, P. W. N. M. van Leeuwen and J. N. H. Reek, Chem.
Commun., 2003, 2474; (b) V. F. Slagt, P. W. N. M. van Leeuwen and
J. N. H. Reek, Angew. Chem., Int. Ed., 2003, 42, 5619.
7 See supporting information.
8 (a) A. W. Kleij, M. Kuil, D. M. Tooke, M. Lutz, A. L. Spek and
J. N. H. Reek, Chem.–Eur. J., 2005, 11, 4743; (b) A. W. Kleij, M. Lutz,
A. L. Spek, P. W. N. M. van Leeuwen and J. N. H. Reek, Chem.
Commun., 2005, 3661.
9 Bulky mono-phosphite Rh-complexes are formed, see: (a)
P. W. N. M. van Leeuwen and C. F. Roobeek, J. Organomet. Chem.,
1983, 258, 343; (b) T. Jongsma, G. Challa and P. W. N. M. van
Leeuwen, J. Organomet. Chem., 1991, 421, 121; (c) A. van Rooy,
E. N. Orij, P. C. J. Kamer and P. W. N. M. van Leeuwen,
Organometallics, 1995, 14, 34.
10 High-pressure IR showed HRh(CO)2(3(h + d)) (ee-isomer) (ref. 7).
11 L. A. van der Veen, M. D. K. Boele, F. R. Bregman, P. C. J. Kamer,
P. W. N. M. van Leeuwen, K. Goubitz, J. Fraanje, H. Schenk and
C. Bo, J. Am. Chem. Soc., 1998, 120, 11616.
12 S. C. van der Slot, J. Duran, J. Luten, P. C. J. Kamer and P. W. N. M. van
Leeuwen, Organometallics, 2002, 21, 3873.
Notes and references
1 See for example: (a) K. Nozaki, N. Sakai, T. Nanno, T. Higashijima,
S. Mano, T. Horiuchi and H. Takaya, J. Am. Chem. Soc., 1997, 119,
4413; (b) G. Francio, F. Faraone and W. Leitner, Angew. Chem., Int.
Ed., 2000, 39, 1428; (c) S. Breeden, D. J. Cole-Hamilton, D. F. Foster,
G. J. Schwarz and M. Wills, Angew. Chem., Int. Ed., 2000, 39, 4106; (d)
I. del Rio, W. G. J. de Lange, P. W. N. M. van Leeuwen and C. Claver,
J. Chem. Soc., Dalton Trans., 2001, 8, 1293; (e) K. Nozaki, T. Matsuo,
F. Shibahara and T. Hiyama, Organometallics, 2003, 22, 594; (f)
13 S. Deerenberg, P. C. J. Kamer and P. W. N. M. van Leeuwen,
Organometallics, 2000, 19, 2065.
14 G. J. H. Buisman, E. J. Vos, P. C. J. Kamer and P. W. N. M. van
Leeuwen, J. Chem. Soc., Dalton Trans., 1995, 409; notable exceptions of
ligands coordinating in an ea-fashion giving high ee see ref. 1a and
R. Edwalds, E. B. Eggeling, A. C. Hewat, P. C. J. Kamer,
P. W. N. M. van Leeuwen and D. Vogt, Chem.–Eur. J., 2000, 6, 1496.
This journal is ß The Royal Society of Chemistry 2006
Chem. Commun., 2006, 4679–4681 | 4681