Dependence of enantioselectivity on the distribution of a chiral hydrogenation catalyst between an aqueous and a micellar phase: investigations using pulsed field gradient spin echo NMR spectroscopy.

Abstract

The enantioselectivity obtained from rhodium complex catalyzed hydrogenations conducted in water can often be increased considerably by the addition of amphiphiles. At present the reasons for this increase in selectivity are not fully understood. The application of pulsed field gradient spin echo NMR (PGSE-NMR) spectroscopy to determine the average diffusion coefficients of the catalysts in both known and novel examples of asymmetric hydrogenation shows definitively that the increase in enantioselectivity is coupled with an aggregation of the catalyst to the micelles. This aggregation or solubilization of the catalyst in the micelles leads to the formation of a new colloidal phase in the aqueous solution. This phase has stronger hydrophobic properties, and thus the hydrogenation is more comparable to those conducted in a hydrophobic or less polar organic solvent. In the case of anionic amphiphiles, which form amphiphilic salts with the cationic catalyst, the embedment of the catalyst complex into the micelle is generally complete. The whole hydrogenation then takes place exclusively inside the micelles, leading to high enantioselectivity. If the catalyst is not completely embedded into the micelle, for example in the cases of nonionic or cationic surfactant solutions, the solubility of the substrate plays an important role. For soluble substrates the hydrogenation of the substrate occurs predominately in the aqueous phase itself, leading to very poor enantioselectivities. In these cases, only the use of a large excess of amphiphile, far above the critical micelle concentration (cmc), will lead to higher enantioselectivities due to a shift of the equilibrium towards the micellar bonded forms of catalyst and substrate. In contrast, poorly soluble substrates exhibit a high tendency to be incorporated into micelles, which leads to much higher enantioselectivities if the cmc of the surfactant is small enough. Changes in the cmc of amphiphiles caused by their aggregation with catalysts could also be estimated. The variation in selectivity observed for the catalysts containing seven-membered, flexible chelate rings is apparently due to changes in their conformation in the less polar micellar medium, and this effect is also seen in organic solvents. As expected, catalysts containing smaller chelate rings show this effect to a considerably lower extent since they are conformationally more rigid.