Multicomponent approach to silica-grafted peptide catalysts : A 3 D continuous-flow organocatalytic system with on-line monitoring of conversion and stereo-selectivity

Abstract

The derivatization of organocatalysts with functional appendages suitable to anchor onto solid supports is usually achieved by stepwise syntheses. As an alternative to such a strategy, this work describes a one-pot approach to silylated prolyl-peptide catalysts by a multicomponent reaction that enables the simultaneous incorporation of the catalytic and the heterogenizable (triethoxysilane) moieties. A microreactor with high catalytic efficacy and reproducibly in the conjugate addition of aldehydes to nitroolefins was obtained by grafting onto HPLC-grade silica (10 μm) and packing into a column with a selected catalyst. A 3 D continuous-flow system that includes the on-line monitoring of the reaction outcome was set up. For that, the microreactor was coupled to a chromatographic column for the separation of the remaining substrates from the Michael adduct in the second dimension, followed by a chiral polysaccharide column for the analysis of conversion and stereoselectivity. This approach represents a new instrumental setup that combines the advantages of multidimensional chromatography and flow catalysis.