Peptide-based Organocatalyst on Stage: Functionalizing Mesoporous Silica by Tetrazine-Norbornene Ligation

Organocatalysis via the enamine mechanism developed to one of the most relevant tools in carbonyl chemistry and is widely used in asymmetric organic synthesis. In this work, a strategy is presented to conveniently immobilize a peptide-based catalyst on silica supports for use in continuous flow catalysis reactions. A set of different porous silica supports is investigated spanning from mesoporous silica particles with defined pore sizes suitable for packed bed column reactors to silica monoliths with hierarchical meso-macropore spaces. While the silica supports are functionalized with norbornene entities, the peptide-based organocatalyst is modified with a tetrazine moiety, enabling the immobilization via inverse electron-demand Diels-Alder (IEDDA) reaction. The ligation results in catalyst loadings up to 0.2 mmol g-1, without compromising the mesopore network. The catalytic activity of the materials is proven by the asymmetric C-C coupling reaction of n-butanal to ss-nitrostyrene proceeding in high yield and enantioselectivity in both batch and continuous flow setups. Tetrazine-Norbornene ligation through inverse electron-demand Diels-Alder reaction has been employed as a novel strategy to immobilize a peptide-based catalyst onto different mesoporous silica supports. Functionalized silica monoliths as well as silica particles in packed bed reactors have been applied in the enantioselective flow catalysis of the addition reaction between ss-nitrostyrene and n-butanal.+image