Molecular weight enlargement : a molecular approach to continuous homogeneous catalysis

Homogeneous catalysts play an increasingly important role in organic synthesis today, because of their high activity and selectivity. Usually, precious metals are used in combination with valuable ligands and since metal prices are expected to increase further in the future, methods for their efficient recycling and reuse are of utmost importance. A range of approaches have been studied over the years, all with their own strengths and weaknesses, leading to the conclusion that one ultimate solution does not exist. This is inherently due to the vast variety of applications, each with its own specific requirements and conditions. Hence, there is a great need for the development of complementary generic methods - a toolbox for practical application. These methods can roughly be divided in biphasic catalysis and immobilization on insoluble (heterogenization) and soluble supports (molecular weight enlargement, MWE). Molecular weight enlargement (MWE) is an attractive method for homogeneous catalyst recycling. Applications of MWE in combination with either catalyst precipitation or nanofiltration that have demonstrated their great potential as a method for process intensification in homogeneous catalysis are discussed in chapter 1. Selected, recent advances in MWE in combination with catalyst recovery are discussed, together with their implication for future developments. These examples demonstrate that this strategy is applicable in many different homogeneously catalyzed transformations. In chapter 2 a new synthetic route towards stable molecular-weight enlarged monodentate phosphine ligands via ‘click’ chemistry is described. These ligands were applied in the Pd-catalyzed Suzuki-Miyaura coupling of aryl halides and phenyl boronic acid. The supported systems show very similar activities compared to the unsupported analogues. Moreover, recycling experiments by means of nanofiltration using ceramic nanofiltration membranes demonstrate that these systems can be recovered and reused efficiently. Chapter 3 describes a simple and efficient approach for the molecular weight enlargement of a hydroformylation catalyst. This system has been applied for the production of aldehydes in a continuous flow nanofiltration reactor operating for an unprecedented period of up to two weeks, without showing typical deactivation or leaching phenomena. Based on a bulky, rigid and robust POSS-modified PPh3 ligand we found that the molecular weight enlarged catalyst combines for the first time efficiently recovery with the advantages that homogeneous catalysts exhibit over heterogeneous systems, such as high activity and selectivity. In chapter 4, the simple and efficient approach for the molecular weight enlargement of a hydroformylation catalyst (chapter 3) has been extended to ligands that are expected to show a better performance than PPh3. Besides the bidentate ligands DPEphos and Xantphos that are known for their higher regioselectivity in the Rh-catalyzed hydroformylation of 1-octene, a bulky monophosphite has been modified with POSS. In this way a very active and recyclable ligand was obtained. These ligands were applied in the continuous hydroformylation of 1-octene in the continuous flow membrane reactor. XantPOSS showed long-term stability under the conditions applied, but showed a rather peculiar regioselectivity pattern, whereas monoPOSSphite showed rapid loss in catalytic activity. In both cases, however, both Rh and P losses were extremely low. Chapter 5 reports on the Rh-catalyzed hydroformylation of styrene. Usually, this reaction yields predominantly the chiral, branched aldehyde. An inversion of regioselectivity can be achieved by using strong p-acceptor ligands, such as diphosphites or diphosphorodiamidite ligands. Binaphthol-based ligands have been investigated spectroscopically and structurally to obtain valuable information on the coordination geometry and the electronic properties of the ligands. The ligands that perform best in the Rh-catalyzed hydroformylation of styrene were enlarged with a POSS moiety, which enables their potential application in a continuous flow membrane reactor. The Dupont adiponitrile process is a large scale industrial process that consists of three reaction steps that are all nickel catalyzed. The isomerization of 2-methyl-3-butenenitrile (2M3BN) to 3-pentenenitrile (3PN) is the second step in this process. In chapter 6, the bidentate ligands sixantphos, DPEphos, Triptycene-PPh2, and BIPPP were studied in the nickel-catalyzed isomerization of 2M3BN to 3PN. Triptycene-PPh2 showed the highest activity in this reaction and was compartmentalized inside a ceramic nanofiltration membrane. For the first time, the catalyst could be efficiently recycled and reused for 7 consecutive runs in this reaction. In order to maximize the catalyst retention, POSS-enlarged ligands were applied, but the catalytic activity decreased dramatically. The ‘click’ dendritic monodentate ligands described in chapter 2 showed approximately the same catalytic activities as their unmodified analogues in the Pd-catalyzed Suzuki coupling reaction. Therefore attempts were undertaken to extend this synthetic strategy to bidentate ligands.