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

• Published in: Journal of catalysis 2012-11, Vol.295, p.179-185
• Main Authors: Ötvös, Sándor B., Mándity, István M., Fülöp, Ferenc
• Format: Article
• Language: English
• Subjects: Aldol reaction; Catalysis; Catalysts; Chemical reactions; Chemical synthesis; Chemistry; Continuous-flow process; Exact sciences and technology; General and physical chemistry; Heterogeneous catalysis; Organocatalysis; Packed bed reactor; Peptides; Pressure; Supported catalysts; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
• ISSN: 0021-9517; 1090-2694
• DOI: 10.1016/j.jcat.2012.08.006

A continuous-flow process was developed for asymmetric aldol reactions utilizing an immobilized peptide as organocatalyst, readily synthesized and immobilized in one single step on a swellable polymer support. Besides being simple and efficient, the described technique tends to be sustainable, as it allows short residence times, ease of product isolation, and remarkable catalyst reusability. [Display omitted] ► An immobilized peptide-catalyzed continuous-flow process for aldol reactions is shown. ► The catalyst was readily synthesized and immobilized by solid-phase peptide synthesis. ► Elevation of the pressure is necessary to maximize conversion of the flow process. ► High productivity was achieved with a short residence time on the catalyst bed. ► The immobilized catalyst is highly recyclable, making the process prominently robust. 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.