Controlling the chiral environment of metal-organic cages for asymmetric catalysis

Details

Supervisors

Singleton, Michael L.

Faculty

Faculté des sciences

Degree label

Master [120] en sciences chimiques, à finalité approfondie

Abstract

Nature often relies on microenvironments derived from complex tertiary structures and a well-defined active site to isolate guest molecules and host chemical transformations with remarkable rate acceleration, substrate specificity, and product selectivity. Drawing inspiration from these systems, chemists have become increasingly intrigued by the prospect that the self-assembly of relatively simple molecular components might generate defined and spatially segregated enzyme-like nanospaces. The field of synthetic self-assembly evolved to leverage a collection of favourable interactions between the building blocks in order to form large entities with increased complexity and functionality. Most notably, coordination-driven self-assembly, which capitalizes on the predictable nature of the metal-ligand coordination sphere and ligand’s ability to encode directionality, has emerged as one quintessential route to design molecules of desired dimensions, sizes, and shapes. In the past four decades, this synthetic strategy has produced a wide range of structural motifs in which organic reactions can be efficiently catalyzed. The origins of the enhanced rates and catalytic selectivities associated with these self-assembled structures are still a matter of debate. However, the properties of the restricted cavity are probably part of the answer. This master thesis aims to provide more fundamental insights into the actual role of the metal-organic assemblies in the observed catalysis. Since the reactivity is assumed to be impacted by the nanocavities’ properties, we hypothesized that a chirally tuned cavity could allow a deeper understanding of the catalytic event via the transfer of chiral information. The development of this new strategy was achieved in three parts. Firstly, we successfully synthesized three rationally designed heteroaromatic amide-based functionalized ligands for the stereo-controlled self-assembly of M4L8 double-walled metallomacrocycles. The functional groups of interest can be described as a methyl group, an acidic group, and a chiral acidic group. Secondly, their self-assembly behaviour in the presence of palladium(II) cations has been studied. Unfortunately, the self-assembly of the chiral variant did not seem to work in contrast to the other ligands. Nevertheless, a comparative study of the reactivity of the acidic and chiral acidic assemblies was still performed as they should be able to catalyze challenging reactions such as a multistep bimolecular reaction sequence to generate cyclic aminal product. The acidic cage efficiently catalyzed the reaction, affording the product in >90% yield after 72h at room temperature. However, no reactivity was associated with the chiral acidic cage. While these results are preliminary, it could already imply the critical importance of the restricted space of the coordination cages for catalysis and leave interesting perspectives for these functionalized M4L8 cages.