Bioinspired Homo- & Heterogeneous Catalysis
provisional Prof. Johannes G. de Vries
The main objective of our research is the development of new catalytic processes. We try to achieve this by studying the relationship between the structure of the catalyst and its performance in catalysis. Our main research interest is in the field of homogeneous catalysis with the aid of transition metal complexes and a broad range of catalytic reactions has been studied. The major activity is in the field of ligand synthesis based on phosphorus donor atoms by rational design assisted by molecular modelling. Ligand design is supported by thorough mechanistic (in-situ) studies of catalytic reactions to acquire insight in structure-activity relations. Besides the study of well-known steric and electronic ligand effects the influence of ligand geometries around the metal centre is a key issue in this research. For example, catalytic reactions can be accelerated by forcing the geometry of the catalyst towards a structure that resembles the transition state, as has been proposed for metalloenzymes. This has resulted in novel, very active and (enantio)selective catalysts.
The rates and selectivity of enzymatic catalysis are seldom equalled by transition metal catalysis. Still, many important fine chemicals are produced by homogeneous catalysis because efficient enzymes for important chemical transformations like CO- and alkene insertions are lacking. By combining the concepts of biology for selective recognition with those of transition metal catalysis we develop novel, highly selective catalysts for important (asymmetric) catalytic C-C bond forming reactions.1 Furthermore, high substrate specificity could allow conversion of a single substrate present in complex mixtures, like those in biological systems.
We have developed methods to introduce phosphine ligand into proteins to introduce non-natural transition metal complexes into proteins.2,3 The protein chain of these artificial metalloenzymes can direct the orientation of the metal center and the substrates. By changing the amino acid sequence and the structure of the catalytic metal complex these catalysts can be optimized to obtain efficient and selective reactions.
We have explored several protein structures such as Photoactive Yellow Protein and Steroid Carrier Protein 2-L. The protein structures have been selected for their substrate binding properties and are applied in several C-C and C-X bond forming reactions2,4 and catalytic hydrogenation.5
 Bioinspired Catalyst Design and Artificial Metalloenzymes. Peter J. Deuss, René den Heeten, Wouter Laan, Paul C. J. Kamer Chem. Eur. J. 2011, 17, 4680-4698.
 Artificial metalloenzymes via cysteine-selective conjugation of phosphines to Photoactive Yellow Protein. W. Laan, B. K. Muñoz, R. den Heeten, P. C. J. Kamer ChemBioChem 2010, 11, 1236-1239.
 Highly efficient and site-selective phosphane modification of proteins via hydrazone linkage for the development of artificial metalloenzymes. P. J. Deuss, G. Popa, C. H. Botting, W. Laan, P. C. J. Kamer. Angew. Chem., Int. Ed. 2010, 49, 5315-5317.
 Artificial copper-enzymes for asymmetric Diels Alder reactions. P. J. Deuss, G. Popa, A. M. Z. Slawin, W. Laan, P. C. J. Kamer ChemCatChem 2013, 5, 1184-1191.
 Photoactive Yellow Protein as scaffold for the synthesis of artificial metalloenzymes. R. den Heeten, B. K. Muñoz, G. Popa, W. Laan, P. C. J. Kamer Dalton Trans. 2010, 39, 8477-8483.
 Enzyme activity by design: an artificial rhodium hydroformylase for linear aldehydes. A. G. Jarvis, L. Obrecht, P. J. Deuss, W. Laan, E. Gibson, P. Wells, P. C. J. Kamer. Angew. Chem. Int. Ed. 2017, 56, 13596-13600.
SCP—2L contains a large apolar molecular tunnel and this binding-sites can be modified with suitable transition metal complexes. The protein has been modified by mutagenesis to obtain one unique cysteine at the desired position (see Figure 1). The protein can be efficiently and selectively modified with phosphines and phosphine-metal complexes. These rhodium phosphine modified SCP-2Ls are efficient linear-selective catalysts in the hydroformylation of long-chain alkenes in water.6 SCP-2L A100C–1–P3–Rh showed a rate enhancement of at least 103 compared to the traditional Rh/TPPTS system in the biphasic hydroformylation of 1-octene and 1-decene. Moreover, the reaction is performed at 35 ℃ instead of the industrial high temperature of 115 ℃.
The current synthesis of fine chemicals is mainly based on fossil resources. With a view to the future, it will be necessary to develop new techniques using bio-based materials as renewable sources for such processes. Against this background the cultivation of oil plants, which can be grown in varying vegetation zones, will pave alternative ways to known and novel chemicals.
Up until now, various procedures have been established for the cleavage of plant oils into fatty acid derivatives and glycerol. The chemical modification of fatty acids and here, in particular, of their double bounds, has already been investigated in detail. The utilization of the cheap by-product glycerol (content in plant oil: ~10 weight percent) remained confined on the synthesis of unsymmetrical and easy accessible compounds, like glycerol carbonate (4-hydroxymethyl-1,3-dioxolan-2-one). In contrast, the generation of symmetrical glycerol derivatives, such as 1,3-dihydroxyacetone, is elaborate and expensive at this point in time.
Based on our previous investigations and on our expertise in the chemistry of renewables we plan to develop a catalytically based synthesis concept which provides an improved access to glycerol-derived symmetrical C3-compounds as valuable fine chemicals, building blocks or monomers.
1. J. Deutsch, A. Martin, H. Lieske, J. Catal. 2007, 45, 428-435.
2. G. Walther, J. Deutsch, A. Martin, F.-E. Baumann, D. Fridag, R. Franke, A. Köckritz, ChemSusChem 2011, 4, 1052-1054.
3. C. Diehl, G. Brenner, B. Schäffner, A. Köckritz, J. Deutsch, K. Neubauer, WO 001172 A1, 2017.
This project focuses on homogeneous catalysis using (chiral) bidentate ligands that enforce "unusual" geometry's. New bidentate ligands have been designed that force the geometry of the starting complex towards a structure that resembles the transition state. This way the course and rate of catalytic reactions can be directed. Furthermore, the rate and selectivity of an elementary step of a catalytic cycle can be steered by influencing the structure of the initial or product complex. This has been successfully applied in studies of the fundamental aspects of the rhodium-catalysed hydroformylation. The aim is to get more detailed information about the mechanism of a new generation of catalysts based on wide bite angle enforcing ligands. Especially the relation between catalyst structure and selectivity of the reaction is investigated. Asymmetric hydroformylation catalysts based on rhodium and P-chiral phosphine ligands have been developed. The newly developed ligands have been applied in a wide variety of metal complexes leading also to novel palladium and nickel catalysts. A variety of palladium catalysed reactions are being studied which are important in organic synthesis: cross-coupling, allylic substitution, Heck reaction, and carbonylation. Ligand effects and kinetics are key issues in these projects.
The goal of a sustainable society requires the efficient use of renewable or sustainable materials and demands the development of selective new methodologies for the preparation of desirable products. In this context we require:
- A change from traditional stoichiometric, high energy methods that produce huge amounts of chemical waste to mild and clean catalytic processes
- A major step change in chemicals production with fossil fuels being replaced by renewable resources as chemical starter units.
The challenge to change our society’s reliance for chemical production from fossil-fuel based to all-renewable resources is of enormous scale. Lignocellulosic biomass is considered as one of best resources for the sustainable production of energy and chemicals. Lignin is the second most abundant bio-polymer after cellulose and the principle natural source of aromatic carbon. It is a three dimensional, amorphous polymer which consists of methoxylated phenylpropane units. These units are interconnected by different C-O and C-C linkages such as β-O-4, β-β, β-5. Our research focusses on the development of optimal catalysts for ether cleavage in model compounds and native samples of lignin for maximising the potential of lignocellulose as a source of fuels and fine chemicals. Ruthenium catalysts based on wide bite-angle ligands have been explored for efficient ether bond cleavage, a crucial step in lignin degradation.
Steric and electronic properties of series of xantphos ligands to develop an efficient catalyst for lignin depolymerization are being studied. Rational design of an effective catalytic system is being aided by high throughput catalysts synthesis and screening.
Straight forward synthetic methodologies for different type of xantphos ligands are developed in our group. These methodologies are simpler and attractive due to the possibility of scaling up and avoiding tedious purification procedures.
- Oligomerisations (Dr. Bernd Müller)
- Synergy between homogeneous and heterogeneous catalysis (Dr. Rajenahally Jagadeesh)