Hydroformylation reactions with rhodium-complexed dendrimers on silica

Article abstract of DOI:10.1021/ja983764b

Polyamidoamine dendrimers, constructed on the surface of silica, were phosphonated by using diphenylphosphinomethanol, prepared in situ, and complexed to rhodium by use of [Rh(CO)₂Cl]₂. Excellent selectivities, favoring the branched aldehydes obtained from aryl olefins and vinyl esters, were observed by using the Rh(I) complex as the catalyst in hydroformylation reactions. The heterogeneous Rh (I) catalyst can also be recycled and reused without significant loss of selectivity or activity.

Full text of DOI:10.1021/ja983764b

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Hydroformylation reactions with rhodium-complexed dendrimers
on silica
Bourque, S. Christine; Maltais, François; Xiao, Wen-Jing; Tardif, Olivier;
Alper, Howard; Arya, Prabhat; Manzer, Leo E.
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Journal of the American Chemical Society, 121, 13, pp. 3035-3038, 1999-03-17
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J. Am. Chem. Soc. 1999, 121, 3035-3038
3035
Hydroformylation Reactions with Rhodium-Complexed Dendrimers
on Silica
S. Christine Bourque,† Franc¸ois Maltais,† Wen-Jing Xiao,† Olivier Tardif,†
Howard Alper,*,† Prabhat Arya,‡ and Leo E. Manzer§
Contribution from the Department of Chemistry, UniVersity of Ottawa, 10 Marie Curie St.,
Ottawa, Ontario, Canada K1N 6N5, Steacie Institute for Molecular Sciences, National Research Council
Canada, 100 Sussex Dr., Ottawa, Ontario, Canada K1A 0R6, and DuPont Central Research &
DeVelopment, Experimental Station, Wilmington, Delaware 19880-0262
ReceiVed October 28, 1998
Abstract: Polyamidoamine dendrimers, constructed on the surface of silica, were phosphonated by using
diphenylphosphinomethanol, prepared in situ, and complexed to rhodium by use of [Rh(CO)2Cl]2. Excellent
selectivities, favoring the branched aldehydes obtained from aryl olefins and vinyl esters, were observed by
using the Rh(I) complex as the catalyst in hydroformylation reactions. The heterogeneous Rh (I) catalyst can
also be recycled and reused without significant loss of selectivity or activity.
Introduction
potentially recyclable while maintaining high catalytic ef-
ficiency. To date, the majority of research in this area has
focused on polymer supported catalysts.4b Normally, the im-
mobilization of a catalytic species on a polymer support is
accompanied by a significant loss in catalytic activity or
selectivity. A variation on the polymer support approach is to
use a dendrimer that can be easily precipitated out of the reaction
solution and recovered with use of microporous membrane
filtration.
Dendrimers, being introduced within the last 20 years, are a
relatively new class of molecules.5 The highly branched nature
of dendrimers offers many interesting characteristics and ap-
plications including multiple sites for metal coordination. In
1994, van Koten and co-workers prepared soluble polycarbosi-
lane dendrimer complexes of nickel(II).6 The latter effectively
catalyzed the addition of polyhaloalkenes to double bonds. In
1997, Reetz and co-workers used a polyaminodiphosphine
dendrimer as a support for rhodium and palladium catalysts.7
We have now developed heterogeneous polyaminoamido diphos-
phonated dendrimers built on a silica gel core support (PPh2-
PAMAM-SiO2). We were gratified to observe that these
dendrimers, when complexed to Rh(I), are excellent catalysts
for the hydroformylation reaction.
The hydroformylation reaction,1 a versatile method for the
functionalization of carbon-carbon double bonds, is one of the
largest industrial catalytic processes producing millions of tons
of aldehydes annually. The majority of industrial applications
involve the production of linear aliphatic aldehydes such as
butanal or nonanal from propene and octene, respectively. The
branched aromatic aldehydes are more important from the fine
chemicals viewpoint as they provide valuable intermediates for
the pharmaceutical industry. For example, the synthesis of
ibuprofen and naproxen, common anti-inflammatory agents, can
be achieved by the mild oxidation of the branched aldehyde of
4-isobutylstyrene and 6-methoxy-2-vinylnaphthalene, respec-
tively.2 In both cases, the S-enantiomer is the pharmacologically
active species while the R-enantiomer is benign. However, in
the case of ibuprofen an asymmetric synthesis is not crucial
since the body efficiently converts the benign R-enantiomer into
the biologically active S-enantiomer.3
In recent years, major efforts have been directed toward the
development of new catalytic systems that effectively combine
the advantages of both heterogeneous and homogeneous ca-
talysis.4 Such a catalyst would ideally be easily recoverable and
† University of Ottawa.
Results and Discussion
‡ National Research Council Canada.
§ DuPont Central Research & Development.
(1) Preparation of PAMAM-SiO2 Dendrimers. Polyami-
noamido (PAMAM) dendrimers, up to the 4th generation, were
constructed on the surface of a silica gel particle (35-70 mm),
with aminopropyl groups (0.9 mmol/g ( 0.1) protruding from
the surface. Standard dendrimer building methods pioneered by
(1) (a) Ungvary, F. Coord. Chem. ReV. 1997, 167, 233-260. (b) Dickson,
R. S. Homogeneous Catalysis with Compounds of Rhodium and Iridium;
D. Reidel: Boston, MA, 1985; Chapter 4. (c) Herrmann, W. A.; Cornils,
B. Angew. Chem., Int. Ed. Engl. 1997, 36, 1048-1067.
(2) (a) Reuben, B. G.; Wittcoff, H. A. Pharmaceutical Chemicals in
PerspectiVe; John Wiley: New York, 1989. (b) Tamao, K.; Sumitami, K.;
Kiso, Y.; Zembayashi, M.; Fujioka, A.; Kodama, S.; Nakajima, I.; Minato,
A.; Kumada, M. Bull. Chem. Soc. Jpn. 1976, 49, 1958-1969.
(3) (a) Nonsteroidal Anti-Inflammatory Drugs; Lewis, A. J., Furst, D.
E., Eds.; Dekker: New York, 1994. (b) Hutt, A. J.; Caldwell, J. J. Pharm.
Pharmacol. 1983, 35, 693-704. (c) Caldwell, J.; Hutt, A. J.; Fournel-
Gigleux, S. Biochem. Pharma. 1988, 37, 105-114.
(4) (a) Shuttleworth, S. J.; Allin, M.; Sharma, P. K. Synthesis 1997,
1217-1239. (b) Nozaki, K.; Itoi, Y.; Shibahara, F.; Shirakawa, E.; Ohta,
T.; Takaya, H.; Hiyama, T. J. Am. Chem. Soc. 1998, 120, 4051-4052. (c)
Chen, J.; Alper, H. J. Am. Chem. Soc. 1997, 119, 893-895. (d) Nait Ajjou,
A.; Alper H. J. Am. Chem. Soc. 1998, 120, 1466-1468.
(5) (a) Matthews, O. A.; Shipway, A. N.; Stoddart, J. F. Prog. Polym.
Sci. 1998, 23, 1-56. (b) Frechet, J. M. J.; Hawker, C. J.; Gitsov, I.; Leon,
J. W. Pure Appl. Chem. 1996, 10, 1399-1425. (c) Ardin, N.; Astruc, D.
Bull. Soc. Chim. Fr. 1995, 132, 875-909.
(6) Knapen, J. W. J.; van der Made, A. W.; de Wilde, J. C.; van Leeuwen,
P. W. N. M.; Wijkens, P.; Grove, D. M.; van Koten, G. Nature 1994, 372,
659-663.
(7) (a) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem., Int.
Ed. Engl. 1997, 36, 1526-1529. (b) Reetz, M. T. Top. Catal. 1997, 4, 187-
200.
10.1021/ja983764b CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/17/1999

3036 J. Am. Chem. Soc., Vol. 121, No. 13, 1999
Bourque et al.
Tomalia and co-workers8 were employed to propagate the
dendrimer generation. A Michael-type addition of the preexisting
amino group to methyl acrylate forms the amino propionate
ester. Subsequent amidation of the ester moieties with ethyl-
enediamine completes the generation. Repetition of these two
reactions produces the desired generation of the dendrimer. As
a crude purification method, simple vacuum filtration and
solvent rinsing served to remove excess reagents.
It must be recognized that the heterogeneity of the dendrimer
on silica does not allow for simple proton and carbon NMR
characterization. It is conceivable that during the preparation
of these dendrimers, several branches may not have reacted
completely resulting in amputated versions of the proposed
structures. An incomplete reaction at one stage will propagate
itself in higher generations.
A recent paper, discovered during the preparation of this
manuscript, by Tsubokawa and co-workers9 explores the grafting
of the same PAMAM dendrimers onto a silica core. They
concluded that the resulting product was more likely to be a
highly branched polymer rather then a true dendrimer especially
at higher generations.
Figure 1. The proposed structures of the generation 0, 1, and 2 Rh-
PPh2-PAMAM-SiO2 complexes.
(2) Preparation of Phosphonated PAMAM-SiO2 Den-
drimer Rhodium Complexes. The dendrimers on silica were
phosphonated in order to provide an attractive coordination site
for rhodium. Double phosphinomethylation of each terminal
amine moiety was carried out with diphenylphosphinomethanol
prepared in situ from paraformaldehyde and diphenylphosphine.7a
The resulting phosphonated dendrimers were characterized by
31P solid-state NMR, with chemical shifts of -27 to -28 ppm
for the various generations comparing well with the published
result of -28 ppm7a for the homogeneous polyamino phospho-
nated dendrimer. The diphosphonated amino group can act as
a bidentate ligand for coordination with many transition metals.
One can envision the formation of a six-membered ring upon
complexation with the metallic species. The phosphonated
dendrimers were readily complexed by reaction with chloro-
(dicarbonyl)rhodium(I) dimer in hexanes. The dendrimer com-
plexes are easily isolated by microporous membrane filtration.
The resulting complexed dendrimers (see Figure 1) were
characterized by 31P solid-state NMR (complexed δ ) 24 to
25 ppm, uncomplexed δ ) -27 to -28 ppm).
Table 1. Rhodium Content of the Various PPh2-PAMAM-SiO2
Dendrimersa
generation
g of Rh/g of Si
µmol of Rh/25 mg of SiO2
0
1
2
3
4
0.046
0.029
0.039
0.0018
0.0026
11.2
7.0
9.5
0.44
0.63
a Average result from two independent laboratories for the same
sample.
(3) Catalytic Hydroformylation of Olefins with Rhodium-
Complexed Silica-Supported Dendrimers. The catalytic activ-
ity of the rhodium-complexed PPh2-PAMAM-SiO2 dendrim-
ers was investigated with regards to the hydroformylation
reaction (eq 1) and the results are summarized in Table 2.
The rhodium-complexed PPh2-PAMAM-SiO2 dendrimers
were digested with hydrofluoric acid or Aqua-Regia by micro-
wave heating and analyzed for Rh content by ICP analysis. The
rhodium content of the various generations is summarized in
Table 1. The degree of complexation decreases significantly
beyond the second generation. This is believed to be due to
incomplete phosphonation reactions arising from steric crowding
and ultimately resulting in the threshold of dendrimer growth
being reached. The PPh2-PAMAM-SiO2 dendrimers can be
handled in air; however, partial oxidation of the phosphine,
detected by 31P NMR analysis (δ ) 30 ppm), occurs after
exposure to atmospheric oxygen for one month. This decom-
position is expedited if filtration of the phosphonated dendrimers
and complexes is not carried out under a flow of inert gas such
as argon or nitrogen. Storage of the dendrimers and complexes
under nitrogen is sufficient to avoid oxide formation.
Treatment of styrene with a 1:1 mixture of carbon monoxide
and hydrogen (1000 psi total pressure) in dichloromethane, and
with Rh-complexed PPh2-PAMAM-SiO2 dendrimer (25 mg),
affords aldehydes in nearly quantitative yield with excellent
regioselectivity at room temperature for generations 0, 1, and
2. The catalytic activity is significantly less at room temperature
when generation 3 and 4 dendrimer complexes are used as
catalysts. Raising the reaction temperature to 65 and 75 °C
decreases the selectivity for the branched aldehyde and increases
the activity of the higher generation catalyst. Decreasing the
total pressure of the reaction to 800 and 500 psi also decreases
the selectivity for the branched aldehyde.
After the hydroformylation reaction with the generation 0,
1, and 2 catalysts, the product solution is yellow in color
suggesting that some leaching of the rhodium metal occurs. This
leaching is less evident in the generation 3 and 4 catalysts. The
catalyst from the entry 4 reaction was recovered by microporous
filtration, washed with distilled hexanes, and reused four times
without significant loss of activity or selectivity. The wash
solution was colorless after the second cycle, consistent with
little, if any, leaching.
(8) (a) Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.;
Martin, S.; Roeck, J.; Ryder, J.; Smith, P. Polym. J. 1995, 17, 117-132.
(b) Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.;
Roeck, J.; Ryder, J.; Smith, P. Macromolecules 1986, 19, 2466-2468. (c)
Tomalia, D. A.; Hall, M.; Hedstrand, D. J. Am. Chem. Soc. 1987, 109,
1061-1063. (d) Tomalia, D. A.; Berry, V.; Hall, M.; Hedstrand, D.
Macromolecules 1987, 20, 1164-1167.
(9) Tsubokawa, N.; Ichioka, H.; Satoh, T.; Hayashi, S.; Fujiki, K.
ReactiVe Functional Polym. 1998, 37, 75-82.

Hydroformylation Reactions with Rh-Complexed Dendrimers
J. Am. Chem. Soc., Vol. 121, No. 13, 1999 3037
Table 2. The Hydroformylation of Styrene with
Rh-PPh2-PAMAM-SiO2 Catalystsa
Table 4. Turnover Numbers for the Hydroformylation of Styrene
with Various Rh-PPh2-PAMAM-SiO2 Dendrimer Catalystsa
catalyst
entry generation
pressureb temp conversionc
selectivityd
B:L
tempb
(°C)
time
(h)
conversion
(%)
turnover
(/h)
(psi)
(°C)
(%)
entry
generation
1
2
3
4
5
6
7
8
9
0
1
2
2
2
2
2
2
3
3
4
4
1000
1000
1200
1000
800
25
25
75
75
75
75
65
25
75
25
75
25
98
25:1
27:1
9:1
8:1
6:1
1
2
3
4
5
6
7
8
9
10
11
12
13
0
0
1
1
2
2
2
2
2
3
3
4
4
25
70
25
22
22
22
22
22
2
4
8
22
72
22
72
22
32
92
15
60
37
44
74
88
82
25
18
38
28
13
102
10
96
18
230
200
120
100
78
180
84
98
>99
>99e
>99
>99
>99
>99
>99
5
70
25
500
3:1
70c
70c
70c
70
1000
1000
1000
1000
1000
1000
13:1
30:1
8:1
10
11
12
NDf
8:1
25
>99
2
70c
25
NDf
70c
200
a 2.0 mmol of styrene, 10 mL pf CH2Cl2, 22 h. b Total pressure with
a 1:1 ratio of CO:H2. c Determined by GC. d Determined by 1H NMR.
e Catalyst was recovered by microporous filtration, washed with distilled
hexanes, and reused four times without significant loss of activity or
selectivity. f Not determined.
a 25 mg of catalyst, 1000 psi of total pressure with a 1:1 ratio of
CO:H2. b 10.0 mmol of styrene at 25 °C, 25.0 mmol at 70 °C except
where indicated. c 10.0 mmol.
reaction (entry 6). The turnover frequency drops by half between
4 and 8 h (entries 7 and 8, respectively) of reaction.
Table 3. The Hydroformylation of Various Olefins Catalyzed by
Rh-PPh2-PAMAM-SiO2 Catalysts
catalyst temp conversionb selectivityc
Summary
entry
substratea
generation (°C)
(%)
B/L ratio
The dendrimer-supported complexes, Rh-PPh2-PAMAM-
SiO2, are new and highly active catalysts for the hydroformy-
lation of a variety of olefins. Aryl olefins and vinyl esters afford
branched chain aldehydes in high selectivity.
1
2
3
4
5
6
7
8
9
isobutylstyrene
4-methoxystyrene
vinylnaphthalene
vinyl benzoate
vinyl benzoate
vinyl benzoate
vinyl acetate
2
2
3
2
2
3
2
2
2
2
2
3
2
2
2
25
75
75
75
25
75
75
65
35
25
25
75
75
75
110
60
>99
>99
>99
29
>99
>99
>99
96
52
95
>99
>99
>99
>99
26:1
7:1
7:1
19:1
21:1
18:1
7:1
13:1
18:1
20:1
18:1
9:1
Experimental Section
vinyl acetate
vinyl acetate
General. Carbon monoxide, a powerful asphyxiant, should be used
with care. To use and work with carbon monoxide safely, reactions
must be carried out in a properly working fumehood with CO detectors
installed nearby.
10 vinyl acetate
11 vinyl acetate
12 vinyl acetate
13 allyl phenyl ether
14 octene
General Procedure for the Preparation of the PAMAM-SiO2
Dendrimers. Aminopropyl silica gel (0.018 mmol NH2, 20.0 g) and
methyl acrylate (0.18 mol, 15.65 g) were stirred at 50 °C under nitrogen
for 3 days in methanol (100 mL). The suspension was cooled and
filtered through a medium pore frit, washed first with methanol (3 ×
30 mL) and then with ether (3 × 30 mL). The residual solvent was
removed in vacuo (96% yield) affording methyl propylaminopropionate
silica gel (0.03 mol of ester groups, 20.0 g). The latter was then added
to ethylenediamine (100 mL) in methanol (100 mL) and stirred at room
temperature under nitrogen for 5 days. The resulting first-generation
PAMAM-SiO2 was isolated by filtration, then washed with methanol
(3 × 30 mL) and dichloromethane (3 × 30 mL). The residual solvent
was removed in vacuo (95% yield).
The second-generation PAMAM-SiO2 can be prepared by following
the above procedure starting with the first-generation PAMAM-SiO2
(0.028 mol of NH2 groups, 20.8 g) and methyl acrylate (0.5 mol, 43.0
g), and by changing the reaction time to 5 days. After isolation, the
ester was added to ethylenediamine (200 mL) in methanol (100 mL)
and stirred at room temperature under nitrogen for 7 days (91% yield).
The third (83% overall yield) and fourth (75% overall yield)
generations were prepared in the same manner.
General Procedure for the Phosphonation of PAMAM-SiO2
Dendrimers. Under argon, diphenylphosphine (40.0 mmol) was added
to a solution of paraformaldehyde (30.0 mmol) in degassed methanol
(40 mL). The mixture was stirred at 70 °C for 30 min and then cooled
to room temperature. The PAMAM-SiO2 dendrimer (2.0 mmol with
respect to NH2) was added along with degassed methanol (20 mL) and
toluene (80 mL). The reaction was stirred at 70 °C for 2 h and then at
room temperature overnight. The product was isolated by filtration by
using a 0.45 µm membrane filter under a stream of argon and washed
with methanol (100 mL). The residual solvent was removed in vacuo
and the product was stored under argon.
2:1
1:2
1:2
15 octene
a 2.0 mmol of substrate, 10 mL of CH2Cl2, 1000 psi of total pressure
with a 1:1 ratio of CO:H2, 22 h (except 48 h for entry 11). b Determined
by GC. c Determined by H NMR.
1
Table 3 describes the catalytic activity of the generation 2
and 3 dendrimer complexes as catalysts with a variety of olefins.
p-Isobutylstyrene gives excellent regioselectivity at room tem-
perature; however, the presence of the isobutyl group in the
para position slows down the reaction compared to styrene.
Excellent selectivity was also observed by reaction of vinyl
acetate at room temperature with a conversion of 52% (entry
10) with the generation 2 rhodium complex as the catalyst.
Increasing the temperature to 35 °C decreases the selectivity
slightly; however, the conversion is nearly complete (entry 9).
Octene reacts to form the linear aldehyde in slight excess.
Increasing the reaction temperature from 75 to 110 °C does not
improve the selectivity (entries 14, 15).
Turnover number results for the hydroformylation of styrene
with various Rh-PPh2-PAMAM-SiO2 dendrimer complexes
as catalysts are presented in Table 4. At room temperature, the
turnover numbers for generations 0, 1, and 2 are generally of
the order of 10 to 20 mmol of substrate to mmol of Rh/h while
generation 3 and 4 afforded 78 and 84/h, respectively. At 70
°C, the generation 3 and 4 dendrimer complexes gave relatively
high turnover frequencies of 180 and 200/h while the lower
generations are of the order of 100/h. The time dependence of
the turnover rate is demonstrated in entries 6-9 where the
highest turnover frequency occurs within the first 2 h of the
General Procedure for the Complexation of PPh2-PAMAM-
SiO2 with Rhodium. The PPh2-PAMAM-SiO2 (1.0 mmol w.r.t. PPh2)

3038 J. Am. Chem. Soc., Vol. 121, No. 13, 1999
Bourque et al.
was added to a solution of [Rh(CO)2Cl]2 (0.25 mmol) in freshly distilled
hexanes (40 mL). The mixture was stirred at room temperature
overnight under nitrogen. The product was filtered through a 0.45 µm
membrane filter under a stream of argon and washed with dry hexanes
(50 mL). Residual hexanes were removed in vacuo.
excess carbon monoxide - hydrogen. The resulting solution was filtered
to remove the catalyst and the solvent was evaporated in Vacuo. The
product aldehydes were analyzed by H NMR spectroscopy and gas
chromatography and identified by comparison of spectral results with
literature data10 and authentic samples.
1
General Procedure for the Hydroformylation Reaction. A glass
liner containing the substrate, catalyst (25 mg), and solvent (10 mL)
was placed in a 45 mL autoclave equipped with a magnetic stirring
bar. The autoclave was flushed three times with carbon monoxide and
then pressurized to the desired level. The hydrogen line was then
attached to the autoclave and purged before pressuring the autoclave
to the desired level. The autoclave was placed in an oil bath preset to
the desired temperature on a stirring hot plate. After the appropriate
reaction time (see Tables 2-4), the autoclave was removed from the
oil bath and cooled to room temperature prior to the release of the
Acknowledgment. We are grateful to DuPont Canada and
to the NSERC/NRC Research Partnership Program for support
of this research.
JA983764B
1
(10) (a) Pouchert, C. J.; Behnke, J. The Aldrich Library of 13C and H
FT NMR Spectra; Aldrich: 1993. (b) Hobbs, C. F.; Knowles, W. S. J. Org.
Chem. 1981, 46, 4422-4427.