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.

Reaktionen in micellaren Systemen

“…Die Übertragung der Chiralität weist darauf hin, dass die Hydrierung in der Palisadenschicht, d. h. im Übergang von Kopfgruppe zum hydrophoben Kern,2a stattfindet. Andere wichtige Hinweise auf einen intramicellaren Mechanismus wurden aus “pulsed‐field gradient spin echo”‐NMR‐Messungen (PGSE‐NMR) gewonnen 159…”

“…Der Anstieg in der Enantioselektivität kann von der Struktur der chiralen Rhodium‐Komplexe abhängig sein. So fanden Selke et al,159 dass Siebenringchelate wesentlich wirksamer als Fünf‐ und Sechsringchelate sind. Die Selektivitätssteigerung beim Übergang von Wasser ins micellare Medium kann übrigens durch das Enantiomerenverhälnis er besser dargestellt werden als durch den Enantiomerenüberschuss ee .…”

Synthesis, X-ray, and NMR Studies on Palladium BINAP Complexes Containing Oxazolidinone and Acetylacetonate Anions

“…Increasingly, pulsed field gradient spin−echo (PGSE) diffusion measurements are used to investigate possible ion pairing and/or aggregation of salts in solution. − The measurement of self-diffusion coefficients ( D values) is especially useful when the cation and anion can be measured separately (e.g., via 1 H and 19 F NMR measurements), as their relative magnitudes can be revealing. In a given solvent, identical D values for the cation and anion suggest strong ion pairing 25 (in the absence of hydrogen bonding, encapsulation effects, etc.).…”

Nuclear Magnetic Resonance Spectroscopy in Homogeneous Hydrogenation Research

“…An example of the use of PGSE NMR spectroscopy can be found in the studies of Selke et al [33], who investigated the dependence of enantioselectivity on the distribution of a chiral hydrogenation catalyst between aqueous and micellar phases. When a compound is incorporated into a micelle, its mobility is much lower compared to its mobility in solution.…”