Supraphos: A Supramolecular Strategy to Prepare Bidentate Ligands

Article abstract of DOI:10.1021/ja038955f

We report a new strategy for the preparation of chelating bidentate ligands, which involves just the mixing of two monodentate ligands functionalized with complementary binding sites. In the current example, the assembly process is based on selective metal?ligand interactions, using phosphite zinc(II) porphyrins 1?6 and the nitrogen donor ligands b?i. From only 16 monodentate ligands, a library of 60 palladium catalysts based on 48 bidentate ligand assemblies has been prepared. The relatively small catalyst library gave a large variety in the selectivity of the alkylation of rac-1,3-diphenyl-2-propenyl acetate. Importantly, small variations in the building blocks lead to large differences in the enantioselectivity imposed by the catalyst (up to 97% ee). Copyright

Full text of DOI:10.1021/ja038955f

Published on Web 03/16/2004
Supraphos: A Supramolecular Strategy To Prepare Bidentate Ligands
Vincent F. Slagt, Marc Ro¨der, Paul C. J. Kamer, Piet W. N. M. van Leeuwen, and Joost N. H. Reek*
Van’t Hoff Institute for Molecular Sciences, UniVersity of Amsterdam, Nieuwe Achtergracht 166,
1018 WV Amsterdam, The Netherlands
Received October 9, 2003; E-mail: reek@science.uva.nl
Bidentate chelating ligands comprise an important class of com-
pounds for the construction of transition metal catalysts.1 As com-
pared to monodentate ligands,2 however, the synthesis is generally
more complex and time-consuming. This is especially inconvenient
for reactions that need intensive ligand-optimization. Methodologies
that enable the synthesis of sufficiently large libraries of bidentate
phosphorus containing ligands are scarce,3 and new strategies are
required to prepare diverse catalyst libraries that can be used for
high throughput experimentation.4 Here, we report a supramolecular
Figure 1. A schematic representation of the supramolecular strategy to
form bidentate ligands by assembly and a modeled structure of a rhodium
complex [HRh(CO)2(1‚b)] based on such a bidentate assembly.
strategy to make bidentate ligands that involves simple mixing of
monomeric ligands. A small combinatorial5 library is used in the
palladium-catalyzed allylic alkylation, yielding up to 97% ee.
Traditionally, bidentate ligands are prepared by attaching donor
atoms to a ligand backbone. We anticipated that monodentate
ligands functionalized with complementary binding motifs could
form bidentate ligands by self-assembly (Figure 1). We have shown
previously6 that zinc(II) porphyrins and nitrogen donor ligands form
a complimentary motive that is suited for this purpose because the
binding is sufficiently strong and selective.7 For the current project,
we prepared six phosphite-functionalized porphyrins (1-6) that in
combination with eight monodentate phosphorus ligands (b-i) give
a library of 48 chelating ligands formed by assembly.
Figure 2. High-pressure 31P NMR spectrum of [HRh(CO)2(1‚b)] in
toluene-d8.
Before studying the ligand library in catalysis, we investigated
the coordination behavior of the supramolecular ligands using
bidentate ligand 1‚b as a typical example.8 UV-vis titrations and
NMR spectroscopy experiments show that the pyridyl moiety of b
coordinates to zinc(II) porphyrin 1 selectively with a binding
constant in the expected range (K(1‚b) ) 3.8 × 103 M-1). The
chelating behavior was proven by the increase in the association
constant of 1‚b observed in the presence of [HRh(a)3(CO)] (K )
64.5 × 103 M-1), corresponding to a chelate effect of 7 kJ/mol.9
NMR-spectroscopy in toluene-d8 under 20 bar of H2/CO. The
31P{1H} NMR spectrum appeared as two doublets of doublets
(δ ) 29.4 and 144.3 ppm, JRh-P ) 143 Hz, JRh-PO3 ) 265 Hz,
JP-PO3 ) 153 Hz) (Figure 2), showing that ligand 1‚b coordinates
in a bidentate fashion. These coupling constants indicate that the
ligand assembly 1‚b coordinates in an equatorial-equatorial fashion
to the rhodium metal center. Importantly, the presence of tri-
phenylphosphine a did not influence the formation of this complex,
and the addition of b to a solution of HRh(CO)2(1)PPh3 resulted
in the formation of the same complex [HRh(CO)2(1‚b)], evidencing
the chelating behavior of the ligand assembly. The chelating
behavior was also reflected in catalysis; in the rhodium-catalyzed
hydroformylation10 of styrene, supramolecular ligand 1‚b shows
an increase in selectivity for the branched product (b/l ) 10) and
a decrease in activity (TOF ) 398) of the catalyst as compared to
1 (TOF ) 2900, b/l ) 2.6). These experiments show that via
selective pyridine-zinc interactions two monodentate phosphorus
ligands form a chelating bidentate ligand assembly.
The supramolecular ligand library based on monodentate phos-
phorus ligands a-i and 1-6 was tested in the palladium-catalyzed
asymmetric allylic alkylation11 of rac-1,3-diphenyl-2-propenyl
acetate using dimethyl malonate as the nucleophile. The matrix of
the supramolecular bidentate ligands gave rise to a catalyst library
of 60 members just from the mixing of stock solutions of the 16
monodentate ligands. For the tested catalysts, the enantiomeric
excess ranged from 85% (S) to 86% (R) (Table 1). Importantly,
the ee depends strongly on the ligand assembly used, both of the
components being important.
The rhodium carbonyl hydride complex HRh(CO)2(1‚b) (δ )
-10.6 ppm) formed by ligand 1‚b was studied with high-pressure
9
4056
J. AM. CHEM. SOC. 2004, 126, 4056-4057
10.1021/ja038955f CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Allylic Alkylation of 1,3-Diphenylallyl Acetate and
Dimethyl Malonate at T ) 25 °C Using Different Palladium
Catalyst Assemblies: Enantiomeric Excesses Are Givena
diversity of the relatively small supramolecular catalyst library is
already sufficient to give catalysts with selectivities ranging from
70% (S) to 60% (R), and, unexpectedly, monomer ligand 3 resulted
even in 97% ee.
ligand
1
2
3
4
5
6
0
0
0
0
0
0
0
0
0
0
0
0
0
0
85 (S)
0
47 (R)
0
40 (S)
23 (S)
4 (S)
45 (S)
42 (R)
11 (S)
86 (R)
0
47 (S)
0
38 (R)
23 (R)
3 (R)
45 (R)
43 (S)
10 (R)
20 (S)
0
59 (S)
0
11 (R)
10 (S)
22 (R)
37 (S)
43 (S)
27 (S)
48 (R)
0
17 (R)
0
33 (S)
5 (S)
0
40 (S)
39 (R)
28 (S)
In conclusion, a new strategy for the preparation of chelating
bidentate ligands is presented. It involves mixing of two mono-
dentate ligands functionalized with complementary binding sites.
In the current example, the assembly process is based on selective
metal-ligand interactions, using phosphite zinc(II) porphyrins 1-6
and the nitrogen donor ligands b-i. From only 16 monodentate
ligands, a library of 60 palladium catalysts based on 48 bidentate
ligand assemblies has been prepared. The relatively small catalyst
library gave a large variety in the selectivity of the alkylation of
rac-1,3-diphenyl-2-propenyl acetate. So far, we only used phosphite
zinc(II) porphyrin 1-6 and monodentate ligands a-i, but many
other (a)chiral building blocks can be used for the ligand assemblies
including those based on hydrogen bonds.15
a
b
c
d
e
f
g
h
i
40 (S)
40 (R)
28 (S)
36 (S)
34 (R)
28 (S)
a [[Pd(allyl)Cl]2] ) 0.1 mmol/L, [1-6] ) 0.6 mmol/L, [a-i] ) 0.6 mmol/
L, the reaction was stopped after 24 h, T ) 25 °C, complete conversion
was obtained in all cases.
Table 2. Allylic Alkylation of 1,3-Diphenylallyl Acetate at T ) -20
°C Using Different Palladium Catalyst Assembliesa
ligand
conv. (%)
eeb (%)
ligand
conv. (%)
eeb (%)
Acknowledgment. The NRSCC is kindly acknowledged for
financial support of this project.
3
56
100
100
100
97 (S)
60 (R)
0
4
54
100
73
96 (R)
60 (S)
42 (S)
70 (S)
3‚b
3‚c
3‚d
4‚b
Supporting Information Available: Experimental details and
characterization data for all new compounds (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
5
44 (S)
5‚b
40
a See Table 1 for conditions. b ee ) enantiomeric excess.
References
Upon using (S)-ortho 3 as a monodentate ligand, we observed
an unexpected high ee (85%, S), because only a few monodentate
ligands are known to give high ee for this reaction.2c The (S)-meta
5 resulted in a much lower selectivity (20% ee, S). Interestingly,
bidentate ligand assembly 3‚b gave the enantiomeric product (47%
ee, R) opposite to that of monodentate 3, probably because in this
system the attack of the nucleophile is trans to the phosphine
ligand,12,13 while bidentate ligand assembly 5‚b gave a higher ee
of the same product as 5 (59% ee, S). Another remarkable result is
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an enantiomeric product other than 3 (48% ee, R). However, in the
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based on ligand assembly 3‚b gave under these conditions an
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