Highly effective and recyclable dendritic BINAP ligands for asymmetric hydrogenation

Article abstract of DOI:10.1039/b001503m

A series of dendritic BINAP ligands have been synthesised and their ruthenium complexes used as catalysts in asymmetric hydrogenation.

Full text of DOI:10.1039/b001503m

Highly effective and recyclable dendritic BINAP ligands for asymmetric
hydrogenation†
Qing-Hua Fan,*a Yong-Ming Chen,a Xiao-Min Chen,a Da-Zhi Jiang,a Fu Xia and Albert S. C. Chan*b
a LMRSS, Center for Molecular Science, Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100080,
P.R. China. E-mail: fanqh@infoc3.icas.ac.cn
b Open Laboratory of Chirotechnology and Department of Applied Biology and Chemical Technology, The Hong
Kong Polytechnic University, Hong Kong, P.R. China
Received (in Cambridge, UK) 23rd February 2000, Accepted 29th March 2000
A series of dendritic BINAP ligands have been synthesised
and their ruthenium complexes used as catalysts in asym-
metric hydrogenation.
chiral diphosphine-containing catalysts, such as Ru(BINAP),
chiral information is transferred from the ligand to the
catalytically active center via the arrangement of the four
phenyl rings of the diphenylphosphino groups.15 Therefore,
upon incorporation of a chiral diphosphine-containing catalyst
into the core of a dendrimer, the chiral information might be
enhanced by the steric bulk of the dendritic wedges and forced
towards the pocket of the catalyst, in which the enantioselective
reaction takes place.
In recent years, the attachment of homogeneous catalysts to
soluble polymer supports has been attracting considerable
attention owing to its potential combination of the advantages,
and minimization of the disadvantages, of homogeneous and
heterogeneous catalysis.1–3 Unlike traditional cross-linked
polymer-supported catalysts in which the structure is usually
not clear, soluble polymer-supported catalysts also offer
opportunities for the study of polymer–catalyst interactions to
fine-tune both catalytic activity and stereoselectivity through
systematically adjusting the microstructure of the catalytic sites
in the polymer supports. Recently, we have developed a soluble
chiral polyester-supported Ru(BINAP) catalyst which offered a
higher rate of reaction than the corresponding monomeric
homogeneous catalyst while retaining high stereoselectivity.4
Most recently, dendritic organometallic catalysts have become
a very active field of research.5–7 The dendrimer architecture
might offer a means of better controlling the disposition of the
catalytic species in soluble polymer-based catalysts. Such novel
catalysts are well defined and highly branched three-dimen-
sional macromolecules on the nano-scale size, which may aid
the recycling of catalysts simply by supra-filtration or solvent
precipitation methods.‡ For asymmetric catalysis, chiral den-
drimers are required, however, so far, very few dendritic chiral
catalysts have been described.8–14 Two general strategies for the
construction of chiral dendritic catalysts can be applied:
multiple chiral metal complexes employed at the periphery of
the dendrimer, or chiral metal complexes incorporated in the
core of the dendrimer. For the second strategy the space-filling
nature of the dendritic wedges near the metal center would alter
the structure of the metal complex, and thus possibly influence
the reactivity of the catalyst and/or the substrate selectivity of
the catalytic reaction with increasing generations. This kind of
dendritic catalyst has been thus termed ‘dendrizyme’.6 For
Here, we report the first use of chiral diphosphine ligands
bearing dendritic wedges for asymmetric hydrogenation.16
BINAP was chosen as a model ligand for this study, since it is
probably the most versatile and effective ligand among all the
chiral phosphine ligands which have been studied for asym-
metric catalysis.15 Both rhodium and ruthenium BINAP
complexes have been extensively studied and several commer-
cial processes based on these catalysts have been developed.17
BINAP itself cannot be easily attached to a dendrimer so (R)-
5,5A-diamino-BINAP (R-1) was synthesized according to the
literature.18 A polyether dendrimer was chosen owing to its
inertness to catalytic reaction. Polyether dendritic wedges 2–4
with carboxyl groups located at the focal point were synthesised
by the convergent-growth approach introduced by Hawker and
Fréchet.19 The chiral dendritic BINAP ligands 5–7 were
synthesised in > 85% yield by condensation of the wedges 2–4
with R-1 in the presence of triphenylphosphite, pyridine and
calcium chloride in N-methyl-2-pyrrolidone (NMP) at 100 °C
(Scheme 1). These ligands were purified by fast column
chromatography and characterized by 1H and 31P NMR
spectroscopy, MALDI-TOF mass spectrometry and elemental
analysis. All results are in full agreement for the proposed
structures.
Asymmetric hydrogenation of 2-[p-(2-methylpropyl)phe-
nyl]acrylic acid 8 was used as the model reaction for the
investigation of the catalytic activity and enantioselectivity of
these dendritic Ru(BINAP) catalysts. In situ catalyst prepara-
tion was attained by mixing a dendritic BINAP ligand with
[Ru(cymene)Cl2]2 in methanol–toluene (1+1, v/v) and stirring
for ca. 40 min at 50 °C. Various generations (5–7) of these
dendritic Ru(BINAP) catalysts were tested, and complete
conversions of 8 were obtained with high enantioselectivities in
24 h with preliminary results summarised in Table 1. For
† Electronic supplementary information (ESI) available: (A) character-
isation of dendritic ligands and in situ catalysts; (B) time-dependent
conversion of 8 catalysed by dendritic catalysts. See http://www.rsc.org/
suppdata/cc/b0/b001503m/
Scheme 1 Synthesis of BINAP ligands with polyether dendritic wedges. Reagents and conditions: (a) NMP, CaCl2, P(OPh3), pyridine, 100 °C, 2 h.
DOI: 10.1039/b001503m
Chem. Commun., 2000, 789–790
This journal is © The Royal Society of Chemistry 2000
789

Table 1 Activity and enantioselectivity in the asymmetric hydrogenation of
8 catalyzed by dendritic Ru(BINAP) complexesa
29904009) and The Hong Kong Polytechnic University for
financial support.
Notes and references
‡ Supra-filtration or solvent precipitation methods are suitable procedures
for small scale high-value processes, but are not viable options for larger
scale lower cost processes.
§ In three-times repeated experiments, the catalysts showed very similar ee
values [experimental error (on a computer-controlled VISTA 6000 gas
chromatograph) is @ ±0.5%]. Further demonstration of the ‘dendrimer
effect’ on enantioselectivity is under way in our laboratory, by using higher
generation dendritic BINAP ligands and exploring the catalysts in other
reactions in which Ru(BINAP)-type catalysts are less effective.
1 For pioneering work using soluble supports, see: E. Bayer and M.
Mutter, Nature, 1972, 237, 512; V. Schurig and E. Bayer, Chemtech,
April, 1976, 212; V. N. R. Pillai and M. Mutter, Acc. Chem. Res., 1981,
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2 For later reviews on soluble polymer-supported catalysts, see: P.
Wentworth and K. D. Janda, Chem. Commun., 1999, 1917; L. Pu, Chem.
Eur. J., 1999, 5, 2227.
3 For later examples of soluble polymer-supported chiral ligand or chiral
catalysts, see: L. Canali, J. K. Karjalainen, D. C. Sherrington and O.
Hormi, Chem. Commun., 1997, 123; H. Han and K. D. Janda, J. Am.
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4 Q.-H. Fan, C.-Y. Ren, C.-H. Yeung, W.-H. Hu and A. S. C. Chan, J. Am.
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6 For reviews on organometallic dendrimers, see: M. A. Hearshaw and
J. R. Moss, Chem. Commun., 1999, 1; G. R. Newkome, E. He and C. N.
Moorefield, Chem. Rev., 1999, 99, 1689.
example, with 0.8 mol% Ru(R-6) catalyst, hydrogenated
product (ibuprofen) was obtained with 92.6% ee and 100%
conversion in 20 h. Confirming the worth of designing
Ru(BINAP) catalysts with dendritic wedges, all of the dendritic
catalysts performed better compared to the parent BINAP
complex. These catalysts showed higher ee values than
Ru(BINAP), although the highest-generation catalyst Ru(R-7)
gave slightly lower enantioselectivity (Table 1, entries 1–4).§
Most interestingly, the size of the dendritic wedges influenced
the reactivity of these catalysts. Unlike common dendritic
catalysts,7a the rate of the reaction increased using higher
generation catalysts. This effect is most pronounced when going
from generation 1 to 2 (Table 1, entries 2–4). The profound size
effect is probably due to the steric bulk of the dendritic wedges
which affects the dihedral angle of the two naphthalene rings in
the Ru(BINAP) complex, and thus leads to a faster rate and/or
better enantioselectivity of reaction. Similar acceleration effects
have been observed in the asymmetric hydrogenation of
unsaturated carboxylic acids catalyzed by Ru(II) catalysts
containing polyester-supported BINAP,4 H8-BINAP20 or a bis-
steroidal phosphine,21 which possess a larger steric bulk than
BINAP itself.
The large molecular size and different solubilities of the
dendritic Ru(BINAP) catalysts in various solvents provided a
convenient and reliable method for the separation and reuse of
the catalysts. For example, upon completion of the reaction,
methanol was added to the reaction mixture and the catalyst
Ru(R-7) was quantitatively precipitated and recovered via
filtration. The recovered catalyst was reused for at least three
cycles with the same activity and enantioselectivity (Table 1,
entries 5–8).
7 For later examples of achiral dendritic catalysts, see: (a) G. E.
Oosterom, R. J. van Haaren, J. N. H. Reek, P. C. J. Kamer and
P. W. N. M. van Leeuwen, Chem. Commun., 1999, 1119; (b) D. de
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Commun., 1999, 2415.
In summary, we have demonstrated the importance of the
dendritic wedges on the catalytic activity and enantioselectivity
of dendritic Ru(BINAP) complexes. This study opens up a new
frontier for the development of highly effective and easily
separable chiral catalysts. Current work is aiming at a detailed
insight of the nature of the dendritic effect and the exploration
of these catalysts in other reactions.
We are grateful to the Foundation of the President of The
Chinese Academy of Sciences and the Foundation of the
Director of Institute of Chemistry, CAS, the National Natural
Science Foundation for Youth of China (projects 29604009 and
17 R. Noyori, Chemtech, 1992, 360.
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790
Chem. Commun., 2000, 789–790