Heterogeneous Dipeptide-Catalyzed α-Amination of Aldehydes in a Continuous-Flow Reactor: Effect of Residence Time on Enantioselectivity

Abstract

A solid-supported dipeptide-catalyzed continuous-flow process was developed for the direct enantioselective α-amination of aldehydes with dibenzyl azodicarboxylate as the electrophilic nitrogen source. With residence time control as an efficient tool for the fine-tuning of the enantioselectivity, synthetically useful α-hydrazino alcohols were achieved with excellent ees. The packed-bed system proved to be highly robust: no decrease in catalyst activity or selectivity was detected throughout 20 h of continuous-flow operation.