Substrate Selective Hydroformylation by a Rh-Catalyst Confined in a Supramolecular Cage

Confinement of the active site is the key reason for high activities and selectivities observed in enzymatic transformations. The intrinsic complexity of natural enzymes has urged chemists to study simpler supramolecular cage analogues to ultimately achieve higher activity and selectivity in known catalytic transformations. Selective encapsulation of catalysts in cages, which should remain throughout the catalytic cycle in competition with substrate molecules, is challenging. One strategy involves the use of ligand templates, i.e. building blocks that can coordinate to the active metal center and simultaneously to the building blocks that form the cage. [1] Although these systems show unrivaled regio-selectivity in e.g. hydroformylation, they are too dynamic to show substrate selective catalysis, which is typical for Natural enzymes. Here we demonstrate that with a rigid cage we can impose size-selectivity on a hydroformylation catalyst upon encapsulation. [2] The encapsulation of the catalytically active complex within the [M₄L₆]⁸⁺ capsule is coordination-driven, relying on the supramolecular pyridine-zinc porphyrin interaction. The windows in the faces of the tetrahedral cage are limited in size due to the steric bulk imposed by the porphyrin units, occupying the edges of the capsule. This results in substrate size selective catalysis, as only smaller substrates can access the Rh(I) catalyst in the cage, and these alkenes are converted into the corresponding aldehydes (Figure 1). The cage acts as a second coordination sphere around the catalytically active site, which bears a strong resemblance to nature where enzymes embed the active site deep inside the hydrophobic pocket of a bulky protein structure.

[1] S.H.A.M. Leenders et al. Chem. Soc. Rev. 2015, 44, 433-448.

[2] S.S. Nurttila et al. Manuscript in preparation.