Asymmetric hydrogenation catalysis via ion-pairing in chiral ionic liquids

The relevant interactions between the organic ions of ionic liquids (ILs) include van der Waals forces, hydrogen bonding and coulombic interactions. In solutions these interactions lead to the formation of aggregates. Depending on the strength of the interactions and the concentration of the IL in the solvent, different aggregates are formed with ion-pairs being the dominant species at low concentrations. A probe for investigating these interactions is the enantioselectivity of a reaction carried out on a prochiral ion in presence of its chiral counter-ion. As asymmetric induction requires structurally well-defined interactions, the induced enantioselectivity can be correlated to ion aggregate formation. The first proof of this concept was provided by the asymmetric hydrogenation of [N-(3′-oxobutyl)-N-methylimidazolium]-[(R)-camphorsulfonate] and -[(S)-camphorsulfonate] using a heterogeneous Ru on C contact. Depending on the substrate IL concentration an enantioselectivity of up to 94% could be realized. The catalytic results were linked to the probability of the ion pair formation as evidenced by DOSY-NMR measurements and dielectric relaxation spectroscopy. The expansion of this principle to chiral ionic liquids that can be easily decomposed to chiral building blocks of synthetic relevance led us to the development of two approaches: a) the application of an IL substrate consisting of a chiral cation and a keto-functionalized, prochiral carboxylate counter-ion allowing for the synthesis of chiral esters in the sequence of IL hydrogenation and esterification; and b) reversible binding of a prochiral substrate to the cation of an IL with a chiral, enantiopure anion allowing the synthesis of neutral chiral building blocks in a sequence of binding, hydrogenation and splitting. The latter approach was tested for two ILs based on the hydroxyl-functionalized cation cholinium to which a prochiral keto functionalized carboxylic acids was reversibly attached via esterification. The hydrogenation of such prochiral ester cation in the presence of enantiopure anions resulted in ees of up to 63%.