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

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 homogeneous 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 Rhand Co-derived catalysts have been developed for hydroformylation 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 developing 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 its applications to study heterogeneous catalysis derived-hydroformylation 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 solidphase 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. 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 * Authors for correspondence. (P.A.) Telephone: (613) 993 7014. Fax (613) 952 0068. E-mail: [email protected]. (H.A.) Telephone: (613) 562 5189. Fax (613) 562 5871. E mail: [email protected]. † 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, 956957. (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-Interscience: New York, 1999. (b) Dörwald, 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. Figure 1. Retrosynthetic analysis: heterogenized catalytic systems with ligands on arms. 2889 J. Am. Chem. Soc. 2001, 123, 2889-2890