Chiral, non-racemic small molecules are playing an increasingly important role in the search for more active and targeted pharmaceuticals. Variations in the structures of these small molecules can have a profound effect of the efficacy, bioavailability, and toxicity of potential drug candidates. The preparation of biologically active compounds can present significant challenges within the pharmaceutical industry on account of the high enantiomeric purities that they must possess.
Organocatalysis is a branch of chemistry that is becoming increasing widespread, in large part because of its applicability to the synthesis of enantiopure small molecules. This approach, which avoids the use of either expensive asymmetric metal catalysts or wasteful resolution processes, is already being employed in drug discovery to achieve a number of pharmaceutically relevant transformations in good yields with high enantioselectivities. Although it represents a general, selective, and practical method in discovery chemistry, the all-organic nature of these catalysts makes them difficult to separate from the desired products. Hence, a new technology is required to render this method viable on an industrial scale. In the past two years, we have demonstrated significant progress toward the understanding of the parameters required in order to achieve catalysis inside nano- and meso-porous materials. We have also shown how to prepare the highly porous and robust frameworks that constitute the recyclable catalyst supports.
The main research objective of this proposal is to design, prepare, and study the effects of immobilizing simple, well-known, homogeneous catalysts in highly porous and chemically resilient nanoporous coordination polymers (NCPs). By introducing organocatalysts into environments that are able to simulate homogenous reaction conditions, while keeping the catalysts bound to the heterogenous scaffolds, we intend to demonstrate that it is possible to use high-cost catalysts in a simple and easily recyclable manner, employing continuous flow chemistry.