Asymmetric aldol reaction in a continuous-flow reactor catalyzed by a highly reusable heterogeneous peptide

Article abstract of DOI:10.1016/j.jcat.2012.08.006

A solid-supported peptide-catalyzed continuous-flow (CF) process was developed for asymmetric aldol reactions. The catalyst was readily synthesized and immobilized by solid-phase peptide synthesis (SPPS) on a swellable polymer support in one single step. Ignoring the peptide cleavage from the resin means no work-up, no purification, and no product loss. After thorough optimization of the reaction conditions, synthetically useful β-hydroxyketone products were obtained in high yields and stereoselectivities. It was found that the heterogeneous catalytic reaction is diffusion-controlled under the present conditions; thus, elevation of the pressure is necessary to maximize conversion of the flow process. Besides being simple and efficient, the described method is also rapid and promisingly productive, with short residence times on the catalyst bed. The immobilized peptidic catalyst is highly recyclable, while further advantageous features are the ease of product isolation and the possibility of facile scale-up, furnishing sustainable catalytic methodology.