As olid-supported dipeptide-catalyzed continuous-flow process was developed for the direct enantioselective a-amination of aldehydes with dibenzyl azodicarboxylate as the electrophilic nitrogen source.W ith residencet ime control as an efficient toolf or the fine-tuning of the enantioselectivity,s ynthetically useful a-hydrazino alcohols were achieved with excellent ees. Thep acked-bed system provedt ob eh ighly robust:n od ecrease in catalyst activity or selectivity was detected throughout 20 ho fc ontinuous-flow operation. UPDATESScheme 2. Solid-supported peptide-catalyzed a-amination of propanal with DBAD as electrophilic nitrogen source, and reduction of the resulting a-hydrazino aldehyde to the correspondingalcohol. 3672 asc.wiley-vch.de

Continuous flow technologies are of considerable current interest. These methods offer several advantages over conventional batch procedures, such as faster heat and mass transfer, shorter reaction time, etc. Herein we show the development of a continuous procedure for the solid‐phase synthesis of protected peptide sequences. Importantly, the synthesis of peptides is more than twice as fast as methods in the published literature. Nonetheless, the protected sequences are constructed in a highly sustainable way, because solvent usage is an order of magnitude lower than those in known literature technologies. The developed method has shown excellent side‐chain protecting group tolerance with a wide range of chemical functionalities. The efficacy of the technology is demonstrated by the synthesis of various calcitonin and corticotropin fragments. Importantly, the products formed with excellent conversion and were isolated in high purity.

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