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

Abstract

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.