Solid-phase catalysis: A biomimetic approach toward ligands on dendritic arms to explore recyclable hydroformylation reactions

Full text of DOI:10.1021/ja003854s

J. Am. Chem. Soc. 2001, 123, 2889-2890
Solid-Phase Catalysis: A Biomimetic Approach
2889
toward Ligands on Dendritic Arms to Explore
Recyclable Hydroformylation Reactions
Prabhat Arya,*,†,‡ Gautam Panda,† N. Venugopal Rao,†
Howard Alper,*,‡ S. Christine Bourque,‡ and Leo E. Manzer§
Steacie Institute for Molecular Sciences
National Research Council of Canada
100 Sussex DriVe, Ottawa, Ontario, Canada, K1A 0R6
Department of Chemistry, UniVersity of Ottawa
10 Marie Curie, Ottawa, Ontario, Canada, K1N 6N5
DuPont Central Research & DeVelopment
Experimental Station, Wilmington, Delaware 19880-0262
ReceiVed NoVember 2, 2000
The hydroformylation reaction is extensively used, on a
commercial basis, to obtain linear and branched aldehydes from
the reaction of alkenes with hydrogen and carbon monoxide in
the presence of a catalyst (i.e., Rh, Co, etc).1 Although homo-
geneous catalysis has been widely practiced in the past, in most
cases, the separation of the products from the reaction mixtures
is a nontrivial undertaking. Over the years, several promising Rh-
and Co-derived catalysts have been developed for hydroformyl-
ation reactions, but the lack of a recycling process severely limits
their potential.2 Due to the high costs involved in the syntheses
of ligands that exhibit high reactivity and high selectivity, and
the use of costly metals (i.e., Rh) in catalysis, there is a growing
interest to explore the heterogenization of the ligands in develop-
ing hetereogeneous catalytic reactions.
With the objectives of the heterogenization of Rh-based metal
catalysts, we initiated a program to explore the applications of
immobilized dendritic ligands anchored onto silica gel3 and onto
polystyrene-based beads4 for hydroformylation reactions. These
systems could be recycled easily, a desired requirement when it
comes to using expensive metals.5 Reasons to explain the observed
reactivity with the heterogenized, dendritic ligands are not clear
at this stage. Due to multiple copies of ligands on dendritic
surfaces, cooperative nature may be one of the several factors,
but it remains to be confirmed.6,5d In addition, to address the issue
of recycling potential of heterogenized catalysts, leaching of the
metals (e.g., Rh in particular) is one of the serious drawbacks
that needs attention. In this communication, we outline a novel
strategy that is targeted to address “the leaching problem” and
Figure 1. Retrosynthetic analysis: heterogenized catalytic systems with
ligands on arms.
its applications to study heterogeneous catalysis derived-hydro-
formylation reactions.
Cognizant of the knowledge that several proteins and enzymes
possess their key functional moieties in the inner core, we decided
to use heterogenized, dendritic systems in which the ligands could
be placed on the inner arms. The plan was to develop a modular
approach that allows the incorporation of ligands at different
interior sites in a highly controlled manner. We relied upon solid-
phase methodology to achieve this goal.7 To place ligands on
arms, we utilized a building block, 3, having two Fmoc-protected
N-terminal NH2 groups required for the growth of the dendritic
macromolecule. In addition, it has two NO2 groups on the side
chain that were converted to ligands via the reduction of NO2 to
NH2 on solid phase, followed by phosphinomethylation.
Heterogenized catalytic systems, 1 and 2 (Figure 1) were
selected to test our biomimetic-based hypothesis that ligands
immersed in dendritic architectures may exhibit a prolonged
reactiVity by preserVing the catalytic sites from the outer
enVironment, and it may preVent the leaching of the metal, etc.8
Both of them bear the same number of ligands (i.e., bivalent) on
the arms but are exposed to very different surroundings. For
example, it is possible to envision that the two catalytic sites in
system 1 are perhaps more exposed when to compared to system
2. It was postulated that, due to its nature, system 2 should have
a sustained effect on the recycling behavior, provided it is not
too hindered to exhibit any reactivity. To our surprise, no
reduction in reactivity was observed in system 2 in comparison
to 1. However, in some cases, system 2 was found to have a
prolonged reactivity over several cycles in hydroformylation
reactions.
* Authors for correspondence. (P.A.) - Telephone: (613) 993 7014. Fax
(613) 952 0068. E-mail: Prabhat.Arya@nrc.ca. (H.A.) - Telephone: (613)
562 5189. Fax (613) 562 5871. E mail: halper@uottawa.ca.
† Steacie Institute for Molecular Sciences, National Research Council of
Canada.
‡ University of Ottawa.
§ DuPont Central Research & Development.
(1) (a) Herrmann, W. A.; Cornils, B. Angew. Chem., Int. Engl. 1997, 36,
1047-1067. (b) For some recent references in homogenized hydroformylation
reactions, see: van der Veen, L. A.; Keeven, P. H.; Schoemaker, G. C.; Reek,
J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Lutz, M.; Spek, A. L.
Organometallics 2000, 19, 872-883; Deerernberg, S.; Kamer, P. C. J.; van
Leeuwen, P. W. N. M. Organometallics 2000, 19, 2065-2072.
(2) Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chem., Int. Engl. 1997, 36,
1236-11256. For a report on applications of dendritic catalysis, see: Tomalia,
D. A.; Dvornic, P. R. Nature 1994, 372, 617-618 and references therein.
(3) (a) Bourque, S. C.; Maltais, F.; Xiao, W.-J.; Tardif, O.; Alper, H.; Arya,
P.; Manzer, L. E. J. Am. Chem. Soc. 1999, 121, 3035-3038. (b) Bourque, S.
C.; Alper, H.; Manzer, L. E. Arya, P. J. Am. Chem. Soc. 2000, 122, 956-
957.
Interest in the design and synthesis of functional, dendritic
macromolecules is growing constantly with applications in
materials and biological sciences.9 Several publications describe
the synthesis of dendritic macromolecules having functional
groups in the interior core.10 However, a modular approach to
place ligands on arms to explore the effect on the leaching of the
metal has not been investigated. To our surprise, it was observed
that the heterogenized dendritic catalysts with ligands on arms
are very reactive in hydroformylation reactions. Moreover, as
anticipated, the two heterogenized catalytic systems 1 and 2
exhibited very different behavior in their recyclable abilities. The
(4) Arya, P.; Rao, N. V.; Singkhonrat, J.; Alper, H.; Bourque, S. C.; Manzer,
L. E. J. Org. Chem. 2000, 65, 1881-1885.
(5) (a) Kobayashi, S. Curr. Opin. Chem. Biol. 2000, 4, 338-345. (b)
Thompson, L. A. Curr. Opin. Chem. Biol. 2000, 4, 324-337. (c) Seebach,
D.; Sellner, H. Angew. Chem., Int. Ed. 1999, 38, 1918-1920. (d) Annis, D.
A.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121, 4147-4154.
(6) (a) Breinbauer, R.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2000, 39,
3604-3607. (b) Kleij, A. W.; Gossage, R. A.; Klein Gebbink, R. J. M.;
Brinkmann, N.; Reijerse, E. J.; Kragl, U.; Lutz, M.; Spek, A. L.; van Koten,
G. J. Am. Chem. Soc. 2000, 122, 12112-12124.
(7) (a) Solid-Phase Organic Synthesis; Burgess, K., Ed.; Wiley-Inter-
science: New York, 1999. (b) Do¨rwald, F. Z. Organic Synthesis on Solid
Phase-Supports, Linkers, Reactions; Wiley-VCH: New York, 2000.
(8) We termed our approach as “biomimetic” because several proteins and
enzymes possess their functional sites in the interior of the macromolecular
architectures, and in several cases it has been shown that the macromolecular
environment play important roles in modulating specific biological responses.
10.1021/ja003854s CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/28/2001

2890 J. Am. Chem. Soc., Vol. 123, No. 12, 2001
Communications to the Editor
Table 1. Hydroformylation of Styrene (p-Methoxystyrene) Using
Scheme 1. Solid-Phase Synthesis of Heterogenized Ligands
Rhodium Complexed Heterogenized Catalytic Systems, 1 and 2a
on Dendritic Armsa
catalyst cycle time (h) temp (°C) conversion (%) branched:linearb
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
1st
1
1
2
45
45
45
45
45
45
45
45
45
45
45
45
45
45
45
45
18
12
14
97
19:1
19:1
19:1
15:1
18:1 (16:1)
17:1 (17:1)
15:1 (17:1)
14:1 (30:1)
16:1
15:1
16:1
16:1 (19:1)
18:1 (16:1)
18:1 (18:1)
17:1 (17:1)
19:1 (30:1)
2nd
3rd
1st
2nd
3rd
4th
5th
1st
2nd
3rd
1st
2nd
3rd
4th
5th
5
20
20
20
20
1
1
2
>99 (>99)
>99 (>99)
>99 (>99)
>99 (56)
23
13
9
96 (>99)
>99 (>99)
>99 (>99)
>99 (>99)
>99 (85)
a (a) (i) 20% piperidine, DMF; (ii) 4.0 equiv 3, 4.0 equiv HBTU, 8.0
equiv DIPEA, DMF, 20h. (b) (i) 20% piperidine, DMF; (ii) 10.0 equiv
4, 10.0 equiv HBTU, 16.0 equiv DIPEA, DMF, 48 h; (iii) 20% piperidine,
DMF; (iv) Ac2O, DIPEA; (c) (i) 20% piperidine, DMF; (ii) Ac2O, DIPEA;
(iii) 12.0 equiv SnCl2 H2O, DMF, 10 h; (iv) 20.0 equiv phosphinomethanol
prepared in situ from p-formaldehyde and Ph2PH in degassed MeOH,
ref 2 h, stirred rt 12 h; (v) 1.0 equiv [Rh(CO)2Cl]2 per NH2 group, CH2Cl2,
rt, 14 h. (d) repeat steps in (c).
5
20
20
20
20
a Reaction conditions: Styrene or p-methoxystyrene (2.0 mmol), CO
(500 psi), H2 (500 psi), catalyst (25 mg). b Ratio of branched:linear
1
aldehydes was determined by H NMR.
effect of the surroundings on their ability to function as different
catalytic systems is highly intriguing and could have impact on
other applications in the area of functional dendritic macromol-
ecules.
Building blocks 3 and 44 were required for the synthesis of
the two heterogenized catalytic systems 1 and 2. Compound 3
was obtained from a Fmoc-protected p-NO2-phenylalanine deriva-
tive (Scheme 1).11
Table 2. Hydroformylation of Vinyl Acetate (Vinyl Benzoate)
Using Heterogenized Catalytic Systems, 1 and 2a
catalyst cycle time (h) temp (°C) conversion (%) branched:linearb
1
1
1
1
1
2
2
2
2
2
1st
5
20
20
20
20
5
20
20
20
20
45
45
45
45
65
45
45
45
45
65
73 (78)
19:1 (20:1)
17:1 (27:1)
17:1 (20:1)
18:1 (30:1)
19:1 (30:1)
20:1 (30:1)
17:1 (30:1)
19:1 (25:1)
18:1 (20:1)
17:1 (19:1)
2nd
3rd
4th
5th
1st
2nd
3rd
4th
5th
99 (>99)
90 (>99)
88 (43)
85 (20)
77 (85)
97 (>99)
95 (>99)
92 (91)
To examine the recycling behavior of the two heterogenized
catalysts 1 and 2 in hydroformylation reactions, styrene, p-
methoxystyrene (see, Table 1), vinyl acetate, and vinyl benzoate
(see Table 2) were selected as substrates. In a typical reaction,
2.0 mmol of the olefin in 10 mL of CH2Cl2 with 25 mg of the
catalyst was treated with CO (500 psi) and H2 (500 psi) gas
mixture in a 1:1 ratio at 45 °C. Catalysts 1 and 2 were found to
be highly reactive for the hydroformylation of styrene. For
example, both catalysts exhibited >99% conversion to the product
(branch:linear ratio ranged from 14:1 to 19:1) even up to the sixth
cycle. With p-methoxystyrene, the catalyst 1 was found to very
reactive up to the fourth cycle (>99%, ratio, B:L, 17:1) but the
conversion to the product decreased to 56% (B:L, 30:1) for the
fifth cycle. Catalyst 2 was found to be equally reactive (> 99%
for the fourth cycle, B:L, 17:1) and a continued reactive behavior
was observed for the fifth cycle (>85%, B:L, 30:1). Similar
observations were made with vinyl benzoate as the substrate. With
catalyst 1, the third cycle exhibited >99% conversion to the
product (B:L, 20:1). The reactivity was significantly reduced for
the fourth (43%, B:L, 30:1) and for the fifth cycles (20%, B:L,
30:1). However, once again the heterogenized catalyst 2 exhibited
a better recycling response. For example, the third cycle with
catalyst 2 gave the product with >99% (B:L, 25:1). Contrary to
88 (83)
a Reaction conditions: Vinyl acetate or vinyl benzoate (2.0 mmol),
CO (500 psi), H2 (500 psi), catalyst (25 mg). b Ratio of branched:linear
1
aldehydes was determined by H NMR.
catalyst 1, complex 2 was appreciably more reactive in the fourth
(91%, B:L, 20:1) and the fifth cycles (83%, B:L, 19:1).
To summarize, we have shown that it is possible to design
heterogenized, dendritic catalytic systems that could exhibit a
better response to the recycling behavior. Our approach is highly
modular and allows for the placement of ligands on arms in a
highly controlled manner. Although the potential of this approach
has only been shown in heterogenized catalytic studies, one may
envision several other applications that may require a precise
positioning of functional moieties in a highly controlled manner.
As observed earlier, the common notion that heterogenized
catalysts exhibit poor reactivities is not true with our present
systems. No reduction in reactivity was observed with the
heterogenized catalyst 2 that bear the two ligands on arms. In
fact, this system exhibited the enhanced recycling potential that
was originally hypothesized. Although results with catalyst 2
clearly indicate a better recycling potential when compared to
system 1, one can only speculate at the moment to explain this
behavior. It is also hoped that the successful outcome with the
present systems may benefit further by applying combinatorial
approaches, thus obtaining even better catalysts with high
reactivities and an everlasting, true catalytic behavior!12
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(11) See Supporting Information for the synthesis of the building block 3
and for the heterogenized catalytic systems 1 and 2.
Acknowledgment. We thank DuPont Canada and NRC/NSERC
Research Partnership Program for financial support of this research.
Supporting Information Available: Experimental details (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
JA003854S
(12) For recent reviews on combinatorial applications in the area of
catalysis, see: (a) Reetz, M. T. Angew. Chem., Int. Ed. 2001, 40, 284-310.
(b) Senkan, S. Angew. Chem., Int. Ed. 2001, 40, 312-329.