A cascade Markovnikov addition/Lewis acid-catalyzed rearrangement of methyleneaziridines and carboxylic acids: continuous-flow synthesis of α-amidoketones

Abstract

α-Amidoketones are essential structural motifs in pharmaceuticals and synthetic chemistry. In this study, we describe a novel synthetic method that involves a cascade addition reaction, followed by a Lewis acid-catalyzed rearrangement of methyleneaziridines and carboxylic acids. Additionally, we developed a high-speed continuous flow synthesis method, allowing the reaction to proceed efficiently within 3.5 minutes. The incorporation of a greener silica gel-packed catalyzed column in this continuous flow system effectively facilitates the rearrangement step, providing a more environmentally friendly approach for synthesizing α-amidoketone compounds.