Dendrimer-induced molecular catalysis in water: The example of olefin metathesis

Article abstract of DOI:10.1002/chem.201002014

A dendritic nanoreactor (see graphic) constructed by 1→3 connectivity and terminated by 27 tetraethyleneglycol tethers induces ring-closing metathesis (RCM), cross metathesis (CM) and enyne metathesis (EYM) using low amounts of Grubbs-II catalyst in water and air, down to 0.04% Grubbs catalyst for RCM. The dendrimer can be re-used at least 10 times without significant yield decrease.

Full text of DOI:10.1002/chem.201002014

DOI: 10.1002/chem.201002014
Dendrimer-Induced Molecular Catalysis in Water: The Example of Olefin
Metathesis
Abdou K. Diallo, Elodie Boisselier, Liyuan Liang, Jaime Ruiz, and Didier Astruc*[a]
Metallodendritic catalysis, in which the molecular catalyst
is covalently attached to the core or periphery of the dendri-
mer, is a well-developed research area.[1] A dendrimer can
also provide a radial polarity gradient suitable for organo-
for medical applications.[7] Very recently, this group has also
reported a family of enzyme-inspired polymer catalysts from
modular star polymers.[8]
Various efficient, water-soluble, ruthenium–benzylidene
olefin, metathesis catalysts[9] for metathesis of water-soluble
olefins in homogeneous water have been reported, in partic-
ular by Grubbs and by Grela,[10,11] and metathesis of hydro-
phobic olefins in water mixed with another solvent is also
known.[12] In some cases, olefin metathesis of hydrophobic
substrates has also been reported in pure water,[13–15] includ-
ing with the use of ultrasonification[14] or surfactants.[15] This
field is thus the subject of fast-growing attention.[11]
We now report catalysis of ring-closing metathesis
(RCM), cross metathesis (CM) and enyne metathesis
(EYM), in water and air under ambient or mild conditions
using low catalytic amounts (0.083% mol) of a suitably de-
signed dendrimer 1 (that can be re-used many times), and of
Grubbsꢁ second-generation olefin-metathesis catalyst
ACHTUNGTRENNUNGcatACHTUNGTRENNUNGalysis, and this principle was shown by Frꢀchetꢁs group to
accelerate the intradendritic dehydrohalogenation of 2-iodo-
2-methylheptane, proceeding with E1 elimination mecha-
nism, and 1O2-sensitized peroxidation reactions.[2] Another
remarkable case is that of dendrimer-encapsulated palladi-
um nanoparticles for which Crooks et al. showed that den-
drimer encapsulation of such nanoparticle catalysts provides
selectivity, the dendrimer playing the role of an efficient
“nanofilter”.[3] Catalysis by dendrimer-encapsulated molecu-
lar transition-metal catalysts is still unknown, however. Yet,
the function of dendrimers as unimolecular micelles has
been pioneered by Newkome in his seminal publication on
“arborols”,[4] and Tomalia and other groups have also shown
useful dendrimer encapsulation of guest molecules in early
works.[5,6]
A
ACTUHNGTRENNCGUHTUGNREU(NGN =CHPh)Cl2ACHTUNREGTG{NNNU 1,3-bisACUTHNGTRNE(NNUG mesityl)-NHC}ACHTUNTGNUER(NG PCy3)] (2, NHC=
Therefore one can envisage that common and commercial
catalysts could be temporarily encapsulated inside dendri-
ACHTUNGTRENNUNGmers at the same time as substrates for intradendritic cataly-
sis. Application of this idea could be beneficial for catalysis
in pure water, a challenging topic. For this purpose, the den-
drimer should be water-soluble and at the same time be ca-
pable of encapsulating hydrophobic compounds in its hydro-
phobic interior. Polyethyleneglycols (PEGs) are adequate
for the decoration of the dendrimer periphery, because they
insure the water solubility of dendrimers and are also com-
patible with hydrophobic compounds. Indeed, Frꢀchetꢁs
group, followed by many others, showed that PEG-terminat-
ed dendrimers could encapsulate various hydrophobic drugs
The new dendrimer 1 was synthesized by [Fe
induced nona-allylation of mesitylene, followed by photolyt-
ic removal of [Fe
(h5-C5H5)]+,[16] hydrosilylation with chloro-
(h5-C5H5)]+-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
methyldimethylsilane, chloride/azide substitution to give a
known dendritic core,[17] and continuation of the 1!3 con-
nectivity[4] upon “click” reaction with a Percec-type den-
dron[18] functionalized at the focal point with a propargyl
group and on the periphery with triethyleneglycol tethers
(Scheme 1; see the Supporting Information for the experi-
[a] A. K. Diallo, Dr. E. Boisselier, L. Liang, Dr. J. Ruiz, Prof. D. Astruc
Institut des Sciences Molꢀculaires
UMR CNRS N8 5255, Universitꢀ Bordeaux 1
33405 Talence Cedex (France)
Fax : (+33)540-00-69-94
E-mail: d.astruc@ism.u-bordeaux1.fr
1
mental details of the synthesis, the H and 13C NMR spectra
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002014.
and the MALDI TOF mass spectrum). The dendrimer 1 was
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Chem. Eur. J. 2010, 16, 11832 – 11835

COMMUNICATION
Scheme 1.
characterized in particular by the appearance of the 1,2,3-
triazole proton at 7.45 ppm in the 1H NMR spectrum re-
corded in CDCl3, the disappearance of the alkyne and azide
bands in the IR spectrum, the molecular peak at 7234.1
([M+Na]+) as the dominant peak in the MALDI TOF mass
spectrum (calcd for C342H597O117N27Si9: 7212.2), and correct
elemental analysis (calcd C56.95, H8.34; found: C56.37,
H8.33). Size exclusion chromatogram consistently showed a
fully symmetrical elution band (see the Supporting Informa-
Table 1. Ring-closing metathesis reactions using Grubbs second-genera-
tion catalyst 2 and dendrimer 1 in H2O and air at 258C for 24 h.
Substrate
Product
Cat. 2[a] Conv. [%] Conv. [%]
[mol%] without 1 with 0.083% 1
AHCTUNGTRENNUNG
A
B
0.1
0
86[b]
0.1
0.06
0.04
0
0
0
90[c]
66[c]
62[c]
1
tion). The DOSY H NMR experiment provided a diffusion
C
0.1
0.1
6[b]
89[b]
coefficient D=1.36 (ꢀ0.1)ꢃ10ꢁ10 m2 sꢁ1 that led to a hydro-
dynamic diameter of 5.54 (ꢀ0.2) nm for 1 using the Stokes–
Einstein equation, and considering 1 as a sphere (see the
Supporting Information).
D
0
90[c]
Among the commercial Ru–benzylidene metathesis cata-
lysts probed in this system (see the Supporting Information),
the most successful catalyst under these conditions is 2.
Using only water as the solvent in the presence of the
water-soluble dendrimer 1 (less than 0.1% mol vs. sub-
strate), only 0.04% of 2 leads to the RCM of 4 giving 10
with 62% conversion at 258C; 2% of 2 is required under
the same conditions for CM and EYM with 97–99% conver-
sions (Table 1 and the Supporting Information). For elec-
tron-deficient olefins, the CM reactions are found to be
E
F
2
2
27[c]
30[c]
97[c]
99[c]
[a] The % mol of the Ru catalyst 2 in this column are vs. substrate; for
instance 4 mg of 2 dispersed in 47 mg of water corresponds to 0.1% mol
2, vs. substrate. The dendrimer amount of 0.083% mol vs. substrate cor-
responds to 28 mg of 1, that is, 83 mmolLꢁ1 (see the Experimental Sec-
tion). [b] The reaction mixture without the catalyst was analyzed by
1H NMR spectroscopy in CDCl3, following filtration of the Ru catalyst or
resulting residual species, then extraction with diethyl ether [c] The reac-
tion mixture without the catalyst was analyzed by GC (injection of the
extracted diethyl ether solution, see the Supporting Information).
stereoACHTUNGTRENNUNGselective, but require heating to 408C (Schemes 2 and
3). The yields of the isolated CM reaction products 17 and
19 under these conditions are 66 and 83%, respectively, but
drop to 10 and 17%, respectively, in the absence of the den-
drimer 1.
Besides the fact that these reactions are carried out in
pure water and air under mild conditions, another remark-
able feature is that extremely low loading of 2 is used for
RCM. Indeed, the RCM reactions usually provide conver-
sions and yields around 90%, with only 0.1% catalyst 2
(Table 1, entries A–D). We do not find very significant dif-
ferences between reactions carried out under N2 and those
in air (for instance, 60% conversion in air vs. 66% conver-
sion under N2, using 0.06 mol% 2) despite a color change of
the reaction from off white to dark beige in air unlike for re-
actions carried out under N2.
We have verified that the reactions do not yield signifi-
cant amounts of RCM products in the absence of the den-
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D. Astruc et al.
ence of the Ru catalyst inside the dendrimer, although such
a transitory situation is likely for minute amounts of 2 in
view of the marked property of dendrimers to encapsulate
various kinds of substrates.[2–6] The driving force for the in-
teraction of the hydrophobic catalyst 2 and substrates is
their hydrophobicity matching the hydrophobic dendrimer
interior. Note that the required amount of catalyst to reach
high conversions is very low compared to metathesis reac-
tions carried out in (or “on”) various solvents including
water (vide supra). It is especially intriguing that high
amounts of ruthenium catalyst are required to carry out
RCM reactions in the presence of water in the absence of
the dendrimer, which means that the catalyst eventually un-
dergoes some decomposition in water in competition with
RCM of terminal olefins. Thus, we have tested the stability
of the Grubbs-II catalyst 2 in the presence of water at ambi-
ent temperature for 24 h, and found that it is stable in the
absence of olefin substrate. For instance, after stirring
0.1% mol 2 in suspension in water for one day at 258C in
air, the substrate 4 and the dendrimer 1 were then added
and, after an additional day, the results of the RCM reaction
were not significantly changed (80% conversion) compared
to the result indicated in Table 1, entry B (90% conversion)
under the same conditions. This means that the pre-catalyst
2 itself is stable and that the relative instability of 2 during
metathesis in the presence of water (but in the absence of
dendrimer 1) is due to the slow decomposition of the cata-
lytically active species formed during the RCM catalytic
cycle. In particular, it has been shown that the methylene
Scheme 2.
Scheme 3.
drimer 1 under our reaction conditions (see Table 1). For
EYM with 2% of catalyst 2, the conversions decrease from
97–99% in the presence of 0.083% mol of dendrimer 1 to
27–30% in the absence of dendrimer.
As shown earlier, RCM reactions can proceed in the pres-
ence of water even without surfactant, but the amount of
first- or second-generation Grubbs catalyst required then
reaches 4 to 5% for good- to high-yield reactions,[13] which
is of the order of 100 times more ruthenium catalyst than
under our reaction conditions. We have indeed verified that
these literature results are reproducible with 2.[13b]
Finally, the last key feature of the present system is that
the aqueous solution of the water-soluble dendrimer 1 can
be recycled, because 1 is insoluble in diethyl ether. Re-use
of the aqueous solution of 1 can be carried out subsequent
to filtration of the water-insoluble catalyst after the reaction
and removal of the organic reaction product by decantation
or extraction with diethyl ether. Remarkably, we have been
able to recycle this aqueous dendrimer solution at least ten
times without any significant yield decrease (see Table 2).
species [RuACHTUNGTERNU(NNG =CH2)Cl2ACHUTGTNERNNUG{1,3-bisACHTUNGERTNN(GUN mesityl)-NHC}ACHTNUGTRENN(UGN PCy3)], gener-
ated in the catalytic cycle of RCM reactions involving termi-
nal olefins, is usually highly subject to dimerization and de-
composition in CH2Cl2 or C6H6.[9] Whatever be the decom-
position path of this species in the presence of water, it ap-
pears that such a decomposition is considerably reduced
when the dendrimer 1 is used for the RCM reactions. This
strongly argues in favor of a dendritic protection (probably
by encapsulation) of this reactive species. RCM reactions
need lower amount of catalyst 2 in organic solvents[9] than
in the presence of water, especially in the absence of the
dendrimer 1. Thus the hydrophobic dendrimer interior
should indeed be favorable to protect this intermediate
ruthenium–methylene species from side reactions occurring
in the presence of water.
In conclusion, we have disclosed extremely efficient RCM
metathesis reactions with the commercial Grubbs-II catalyst
2 with high conversions and yields using only 0.1% catalyst
and 0.083% of the new dendrimer 1 in pure water and air at
258C without significant yield decrease in air, compared to
reactions under N2. Under these conditions, the RCM reac-
tions do not significantly proceed in the absence of the den-
drimer 1. The use of the water-soluble dendrimer 1 allows
us to decrease the amount of this commercial ruthenium
catalyst needed to carry out olefin RCM reactions in (or
“on”) water by a factor of the order of 100. Other metathe-
sis reactions such as EYM and CM, which were also carried
out in pure water and air with 2% Grubbs catalyst 2, also
Table 2. Recycling the aqueous solution of dendrimer 1 with the use of
0.1 mol% Grubbs-II catalyst 2 for the RCM of 4.[a]
Cycle number
1
2
3
4
5
6
7
8
9
10
conversion [%, ꢀ3%] 90 89 87 86 87 87 86 86 86 85
[a] The catalyst 2 was not recycled, given the low amount of 0.1 mol% 2
(4 mg) used for each experiment. See Table 1, entry B for the lower limit
of the% mol 2 vs. 4 (0.04%). Conversions were determined by GC (see
the Experimental Section and the Supporting Information).
The reaction mixtures are heterogeneous in these systems,
that is, 2 is in equilibrium between the solid state and the
dendrimer-solubilized state (Scheme 4).
The catalyst 2 looks insoluble under the reaction condi-
tions. Physical data do not permit us to establish the pres-
Scheme 4.
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Heterogeneous Catalysis
COMMUNICATION
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times without significant decrease of metathesis product
yield. This strategy might in principle be extended to other
types of catalysis, and research along this line is ongoing in
our laboratory.
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Grubbs second-generation catalyst 2 (4 mg, 4.71 mmol, 0.1 mol% vs. 4),
the substrate 4 (1.184 g, 4.71 mmol), the dendrimer 1 (28 mg, 3.9 mmol,
83 mmolLꢁ1, that is, 0.083 mol% vs. 4, 83 mol% vs. 2), and distilled water
(47 mL) were introduced into an Erlenmeyer flask, and the resulting het-
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24 h under air. Then, the insoluble ruthenium catalyst 2 was separated
over a 0.22 mm millipore filter (PTFE). The product 10 was then extract-
ed from the reaction mixture with diethyl ether, and analyzed by GC (a
sample of this diethyl ether phase of the reaction mixture was directly in-
jected), which provided a 90% conversion to 10. The ether solvent was
also removed under vacuum for 1H NMR analysis in CDCl3. The dendri-
mer, which is insoluble in diethyl ether, remained in the aqueous phase.
This aqueous solution of 1 could be re-used with the present procedure
at least ten times without any significant yield decrease for an analogous
reaction (see Table 2 and the Supporting Information). On a 1.0 g scale
of 4 (4 mmol), the yield of the RCM reaction of 4 using the same proce-
dure was 87% (0.773 g, 3.5 mmol) after column chromatography on silica
gel by using pentane/ethyl acetate 9:1. The same experiment in the above
conditions, but carried out in the absence of dendrimer 1, gave 0% con-
version, and 4 was recovered. The procedure for the RCM reactions of 3,
5, and 6 (entries A, C, and D of Table 1) were identical. The same proce-
dure was used with 2 mol% of 2 for EYM of 7 and 8 at 258C giving 13
and 14, respectively (entries E and F, respectively, of Table 1) and CM of
15 and 18 at 408C giving 17 and 19, respectively (Schemes 2 and 3, re-
spectively, see the SI). The detailed experimental procedure for the syn-
thesis of the dendrimer 1 including all characterizations and spectra is
provided in the Supporting Information.
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Acknowledgements
Financial support from the IUF, the Universitꢀ Bordeaux 1, the CNRS
and the ANR (project ANR-07-CPD-05-01) are gratefully acknowledged.
Keywords: dendrimers · Grubbs catalyst · heterogeneous
catalysis · metathesis · water chemistry
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Received: July 16, 2010
Published online: September 6, 2010
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