Soxhlet-dialysis: a method to recover soluble polymer supported catalysts{

There is a widespread interest in developing methods to recover homogeneous catalysts, particularly chiral catalysts, from a reaction mixture. The impetus to recover and reuse homogeneous catalysts stems not only from an economic standpoint but also from the need to eliminate contamination of the transition metal catalyst in the product and in the waste streams. The challenge is to recover the catalyst for reuse without any significant loss in its reactivity and selectivity. We report here a simple method that we call soxhlet-dialysis for the recovery of soluble polymer supported catalysts. Using this method, we show that a PEG-supported titanium-salen complex can be recovered and reused for silylcyanation of benzaldehyde at least five times without any loss of reactivity and enantioselectivity. When compared with normal dialysis, soxhlet-dialysis minimizes the amount of solvent that is required because of the recycling of the solvent through reflux. Among the strategies to recycle catalysts, the use of soluble supports to anchor transition-metal complexes has received considerable attention in recent years. The soluble support ensures that the catalyst is in the same phase as the reactants and reagents. Therefore, the reactivity and selectivity of the catalysts anchored on soluble supports can equal that of the unsupported homogeneous analogs; it is a significant advantage over the catalysts supported on insoluble supports. Initial methods to recover the catalyst for recycling were focused on precipitation and filtration of the supported catalyst by reducing the solubility of the support using an appropriate solvent or by changing the temperature. The precipitated catalyst often shows substantially reduced activity and poor recyclability. More recent methods focus on retaining the catalyst in solution and separating it from the reactants and products. These methods include the use of liquid–liquid biphasic solvent systems and pressurized-filtration using membranes with nanometer-sized pores. We have been interested in using dialysis to recover homogeneous polymer-supported catalysts for recycling. Dialysis relies on a concentration gradient across a semi-permeable membrane and the rate of diffusion declines exponentially as the system approaches equilibrium. In order to re-establish the diffusion gradient, the bulk needs to be periodically replaced with fresh solvent. Therefore, using dialysis to recover catalysts would require large amounts of solvent. To address this issue, we developed a simple semi-continuous-flow dialysis set up using a soxhlet extractor where the thimble is replaced with a dialysis bag (Fig. 1a). The dialyzed solution outside the membrane is continuously replaced with fresh solvent from the reflux, thereby maintaining the diffusion gradient. Of particular concern is the stability of dialysis membranes to organic solvents. However, we found that commercially available Spectra/Por regenerated cellulose membranes are stable to most organic solvents over extended periods of time. We chose the asymmetric silylcyanation of benzaldehyde using a chiral titanium-salen complex as a model reaction. As the soluble polymeric support, we used polyethylene glycol (PEG, Mw 5 5000 Da), which was attached to the catalyst through a glutaric acid spacer (Fig. 1b). A solution of the PEG-supported salen ligand in dichloromethane was treated with an equimolar amount of titanium tetrachloride and allowed to stir at room temperature for one hour to give 1. The solution of the preformed catalyst (0.1 mol% of 1) was treated with equimolar amounts of benzaldehyde and trimethylsilylcyanide (TMCN) (Scheme 1). The reaction proceeded at room temperature and was monitored by GC until complete conversion (.99%) of benzaldehyde to the product was observed. The product, cyanohydrin trimethylsilyl ether, was obtained in 86% ee after 24 h, similar to the previously reported enantioselectivity achieved with the unsupported catalyst 2. The reaction was concentrated and placed into a dialysis tubing (molecular weight cut-off 5 3.5 kDa) with one end tied shut. A magnetic stir bar was then placed into the dialysis bag to