A strongly positive dendrimer effect in asymmetric catalysis: Allylic aminations with Pyrphos-palladium functionalised PPI and PAMAM dendrimers

Article abstract of DOI:10.1039/b302155f

A remarkable and unprecedented increase in catalyst selectivity in dendrimer catalysis is observed for the Pyrphos-Pd catalysed allylic amination of 1,3-diphenyl-1-acetoxypropene as a function of the dendrimer generation (with up to 64 metal sites). This steady increase in ee-values for the allylic amination is less pronounced for the poly(propyleneimine)-derived catalysts than for the corresponding palladium-PAMAM dendrimer catalysts for which an increase in selectivity from 9% ee for a mononuclear reference system to 69% ee for the Pd₆₄-dendrimer was found.

Full text of DOI:10.1039/b302155f

A strongly positive dendrimer effect in asymmetric catalysis: allylic
aminations with Pyrphos-palladium functionalised PPI and PAMAM
dendrimers†
Yann Ribourdouille, Gerald D. Engel, Mireille Richard-Plouet and Lutz H. Gade*a
a
a
bc
a
Laboratoire de Chimie Organométallique et de Catalyse, UMR 7513, Institut Le Bel, Université Louis
Pasteur, 67070 Strasbourg, France. E-mail: gade@chimie.u-strasbg.fr
Institut de Physique et Chimie des Matériaux de Strasbourg UMR 7504,23, rue du Loess, 67037
b
Strasbourg, France
c
Institut des Matériaux Jean Rouxel, Laboratoire de Chimie des Solides 2, rue de la Houssinière, BP32229,
44322 Nantes, France
Received (in Cambridge, UK) 26th February 2003, Accepted 20th March 2003
First published as an Advance Article on the web 23rd April 2003
A remarkable and unprecedented increase in catalyst
selectivity in dendrimer catalysis is observed for the Pyr-
phos-Pd catalysed allylic amination of 1,3-diphenyl-1-acet-
oxypropene as a function of the dendrimer generation (with
up to 64 metal sites). This steady increase in ee-values for the
allylic amination is less pronounced for the poly(propylene-
imine)-derived catalysts than for the corresponding palla-
dium-PAMAM dendrimer catalysts for which an increase in
selectivity from 9% ee for a mononuclear reference system to
behaviour in catalysis to that of the mononuclear systems of
reference.
The chiral Pyrphos-functionalized dendrimers, which we
employed, were both the PPI derivatives mentioned above
(containing 4, 8, 16, 32 and 64 metal binding sites) and the
analogous poly(amidoamine) (PAMAM) dendrimers (contain-
ing 4–64 binding sites) which were synthesized in an analogous
way by ethyl-N,N-dimethylaminopropylcarbodiimide (EDC)
induced amide coupling of the ligand-linker unit 1 with the
amino end groups of the dendrimer (Scheme 1). Stirring
6
9% ee for the Pd64-dendrimer was found.
PPI(Pyrphos)
MAM(Pyrphos)64 with [PdCl
temperature cleanly gave the metallated dendrimers PPI(Pyr-
4
–PPI(Pyrphos)64 and PAMAM(Pyrphos)
4
–PA-
In spite of an ever growing number of examples for the
2
(NCPh) ] in CH Cl at ambient
2
2
2
1
application of metalladendrimers in catalysis there are still
only a few reports on applications in asymmetric catalysis to
date. On the other hand, enantioselective catalytic conversions
phosPdCl
phosPdCl
2
)
)
4
–PPI(PyrphosPdCl and
2
)
64
PAMAM(Pyr-
2
2
4
–PAMAM(PyrphosPdCl )64, respectively. Their
2
31
should be particularly suited as sensitive probes for “dendrimer
effects” in view of the small free activation enthalpy increments
which are associated with the catalyst selectivity.3
complete metallation was established by their P NMR spectra
which displayed a single coordination-shifted resonance at d
42.4–43.0 (d 211.0 to 212.2 for the non-metallated phos-
phines).
4
We recently reported the fixation of the Pyrphos ligand to
the amino endgroups of poly(propyleneimine) (PPI) dendrimers
and the generation of multisite cationic rhodium hydrogenation
catalysts bearing up to 32 metal sites.5 These dendrimer
catalysts displayed reduced activity and selectivity, with respect
to the mononuclear complexes, in the hydrogenation of several
prochiral substrates and thus a pronounced negative “dendrimer
effect”. In this paper we report, for the first time for such
Pyrphos-derived species, a strongly positive effect6 on the
selectivity of an asymmetric catalytic transformation upon
going to very large multisite chiral dendrimer catalysts. This
enhancement of the catalyst selectivity was observed in
palladium catalyzed allylic substitutions which are known to be
particularly sensitive to small changes in the chemical environ-
ment of the active catalyst sites.7
In contrast to the highly charged cationic Pyrphos-rhodium
dendrimers which we previously employed in asymmetric
hydrogenations, the neutral dichloropalladium derivatives
showed no tendency to aggregate significantly in solution or
upon precipitation. This was particularly apparent in prelimi-
nary TEM studies performed on samples of both PPI(Pyr-
2 2
phosPdCl )16 and of PPI(PyrphosPdCl )32 which gave electron
micrographs showing the more or less isolated individual
,8
Several studies on the catalytic properties of palladium
dendrimers bearing achiral phosphines have been recently
reported.9
–11
For the reaction of trans-cinnamyl acetate with
morpholine van Leeuwen and coworkers, using carbosilane
dendrimers, reported a slight increase in the ratio of the
10
branched vs. the linear product, while Kaneda et al. observed
no significant dendrimer effect using these substrates.11 How-
ever, the latter group found an increase in diastereoselectivity of
the amination of cis-3-acetoxy-5-carbomethoxycyclohex-1-ene
upon going to higher dendrimer generations, an observation
which they attributed to the increased surface crowding in these
macromolecular catalysts. Togni et al. reported the application
of chiral phosphinepalladium derivatives to dendrimer cataly-
12
sis. However, this study was limited to low generation
dendrimers which did not display a significantly different
Scheme 1 Synthesis of the Pyrphos-functionalized dendrimers PPI(Pyr-
phos)
their conversion to the metallated dendrimers PPI(PyrphosPdCl
(PyrphosPdCl and PAMAM(PyrphosPdCl –PAMAM(Pyr-
phosPdCl
4
–PPI(Pyrphos)64 and PAMAM(Pyrphos)
4
–PAMAM(Pyrphos)64 and
†
Electronic supplementary information (ESI) available: experimental
2 4
) –PPI-
procedures for the synthesis and metallation of phosphane dendrimers, and
catalytic studies. See http://www.rsc.org/suppdata/cc/b3/b302155f/
)
2 64
2 4
)
2 64
) .
1
228
CHEM. COMMUN., 2003, 1228–1229
This journal is © The Royal Society of Chemistry 2003

metalladendrimers (Fig. 1).‡ The statistical analysis of the
diameters of the metallated features observed in the individual
samples yielded distribution maxima (2.8 and 4.7 nm, re-
spectively) corresponding exactly to the theoretically predicted
values for the two dendrimer generations (Fig. 1b). These
values are consistent with the hydrodynamic radii of the
phosphine precursors determined in solution (1.6 and 2.8 nm,
respectively).
trend was observed in the asymmetric allylic alkylation of
1,3-diphenyl-1-acetoxypropene with sodium dimethyl mal-
onate which indicates that the results of the amination reaction
may be typical for allylic substitutions in general.13
We are currently studying the underlying mechanistic
reasons for this remarkable “dendrimer effect”. It is well known
2 2
that for C -chiral Ph P-diphosphines the orientation of the
phenyl substituents controls the stereoselectivity in the catalytic
transformations. Upon going to the higher dendrimer genera-
tions with their increasingly crowded diphosphine periphery,
the conformational flexibility and preferential orientation of
these aryl substituents may be altered which in turn changes
their selectivity in the allylic substitutions.
This work was funded by the CNRS (France) and the Institut
Universitaire de France. We acknowledge the help of Jean-
Pierre Munch with the determination of the hydrodynamic radii
of some of the dendrimers in solution. We thank the Ministère
de lAEducation Nationale de la Recherche et de la Technologie
and the Studienstiftung der deutschen Volkes for PhD grants to
Y.R. and G.D.E, respectively.
Fig. 1 (a) TEM image of the “fourth-generation” palladadendrimer
PPI(PyrphosPdCl )32 displaying features which belong both to individual
2
molecules as well as the superimposition of several dendrimers. (b)
Statistical size distribution based on the TEM images of PPI(Pyr-
Notes and references
rd
th
2 2
phosPdCl )16 [3 generation] and PPI(P Pd32) [4 generation].
‡ Powder samples are diluted in dimethyl sulfoxide. A droplet is deposited
onto a copper grid (3 mm diameter) and allowed to dry overnight. A film is
obtained and ready for observation in a TOPCON 002 transmission electron
microscope, operating at a 200 kV accelerating voltage. EDX spectroscopy,
coupled to TEM images, allows us to check the presence of Pd in the
particles. Distributions in size are measured on numeric images using
Analysis software (distributed by Eloise). Counting is performed on 200
particles, for each sample. The distribution is fitted to a Gaussian law
centered on 2.8(7) nm, for G3–Pd. For G4–Pd, the distribution is less narrow
and centred on 4.7(7) nm. The broadening at larger diameter takes into
account the elliptical shape of the objects.
As a test reaction for probing the catalytic performance we
chose the well established allylic amination of 1,3-diphenyl-
1
-acetoxypropene with morpholine [eqn. (1)]. The mononuclear
catalyst [(Boc-Pyrphos)PdCl ] (2) is very unselective for this
2
transformation (9% ee) which provides the point of reference
for the subsequent studies with the dendrimer catalysts. Using
complex 2 or the metalladendrimers PPI(PyrphosPdCl
PPI(PyrphosPdCl and PAMAM(PyrphosPdCl –PA-
MAM(PyrphosPdCl 64 in 0.3 mol% catalyst concentration, the
amination of 1,3-diphenyl-1-acetoxypropene was carried out at
5 °C in DMSO. The results of this study (representing the
average values for 3 runs) are displayed in Fig. 2.
2 4
) –
2
)
64
2 4
)
2
)
1
For reviews of dendrimer catalysis, see: (a) G. E. Oosterom, J. N. H.
Reek, P. C. J. Kramer and P. W. N. M. van Leeuwen, Angew. Chem., Int.
Ed., 2001, 40, 1828; (b) D. Astruc and F. Chardac, Chem. Rev., 2001,
4
1
01, 2991.
2
(a) M. S. T. H. Sanders-Hoven, J. F. G. A. Jansen, J. A. J. M. Vekemans
and E. W. Meijer, Polym. Mater. Sci. Eng., 1995, 210, 180; (b) D.
Seebach, R. Marti and T. Hintermann, Helv. Chim. Acta, 1996, 79,
1710; (c) P. B. Rheiner and D. Seebach, Polym. Mater. Sci. Eng., 1997,
77, 130; (d) R. Breinbauer and E. N. Jacobsen, Angew. Chem., Int Ed.,
2000, 39, 3604; (e) C. Köllner, B. Pugin and A. Togni, J. Am. Chem.
Soc., 1998, 120, 10274; (f) R. Schneider, C. Köllner, I. Weber and A.
Togni, Chem. Commun., 1999, 2415; (g) A. Takayoshi and S. Hiroaki,
Tetrahedron: Asymmetry, 2002, 13, 2083.
(1)
3
R. Noyori, Angew. Chem., Int. Ed., 2002, 41, 2008 and refs cited
therein.
4
5
6
U. Nagel, Angew. Chem., 1984, 96, 425.
G. D. Engel and L. H. Gade, Chem. Eur. J., 2002, 8, 4319.
A positive dendrimer effect in the regioselectivity of hydroformylations
was reported recently: L. Ropartz, R. E. Morris, D. F. Foster and D. J.
Cole-Hamilton, Chem. Commun., 2002, 361.
A remarkable and unprecedented increase in catalyst se-
lectivity is observed as a function of the dendrimer generation.
This steady increase in ee-values for the allylic amination is less
pronounced for the PPI-derived catalysts [40% ee for PPI(Pyr-
7 Reviews covering various aspects of asymmetric allylic substitutions:
(a) T. Hayashi, in Catalytic Asymmetric Synthesis, ed. I. Ojima, VCH,
Weinheim, 1993, p. 325; (b) B. M. Trost and D. L. van Vranken, Chem.
Rev., 1996, 96, 395; (c) G. Helmchen and A. Pfaltz, Acc. Chem. Res.,
phosPdCl
catalysts for which an increase in selectivity from 9% ee for 2 to
9% ee for PAMAM(PyrphosPdCl 64 was found. The varia-
2
)64] than for the palladium-PAMAM dendrimer
6
2
)
2
000, 33, 336.
tions of these values observed in catalytic runs with different
catalyst batches were less than (± 0.5% ee). The same general
8
Reviews on allylic amination: (a) M. Johannsen and K. A. Jørgensen,
Chem. Rev., 1998, 98, 1689; (b) A. Heumann, in Transition Metals for
Organic Synthesis, ed. M. Beller and C. Bolm, Wiley-VCH, Weinheim,
1
998, p. 251.
9
(a) M. T. Reetz, G. Lohmer and R. Schwickardi, Angew. Chem., Int. Ed.
Engl., 1997, 36, 1526; (b) N. Brinkmann, D. Giebel, G. Lohmer, M. T.
Reetz and U. Kragl, J. Catal., 1999, 183, 163.
1
0 (a) G. E. Oosterom, R. J. van Haaren, J. N. H. Reek, P. C. J. Kramer and
P. W. M. van Leeuwen, Chem. Commun., 1999, 1119; (b) D. de Groot,
E. B. Eggeling, J. C. de Wilde, H. Kooijman, R. J. van Haaren, A. W.
van der Made, A. L. Spek, D. Vogt, J. N. H. Reek, P. C. J. Kramer and
P. W. M. van Leeuwen, Chem. Commun., 1999, 1623; (c) D. de Groot,
J. N. H. Reek, P. C. J. Kramer and P. W. M. van Leeuwen, Eur. J. Inorg.
Chem., 2002, 1085.
Fig. 2 Dependence of the enantiomeric excesses found for the reaction in
eqn. (1) on the dendrimer generation for both precatalyst series PPI(Pyr-
11 T. Mizugaki, M. Murata, M. Ooe, K. Ebitani and K. Kaneda, Chem.
Commun., 2002, 52.
phosPdCl
MAM(PyrphosPdCl ) .
2 64
2
)
4
–PPI(PyrphosPdCl
2
)
64 and PAMAM(PyrphosPdCl
2 4
) –PA-
12 C. Köllner and A. Togni, Can. J. Chem., 2001, 79, 1762.
13 Y. Ribourdouille and L. H. Gade, unpublished results.
CHEM. COMMUN., 2003, 1228–1229
1229