N‑Heterocyclic Carbene-Mediated Microfluidic Oxidative Electrosynthesis of Amides from Aldehydes

A flow process for N-Heterocyclic Carbene (NHC)-mediated anodic oxidative amidation of aldehydes is described, employing an undivided microfluidic electrolysis cell to oxidize Breslow intermediates. After electrochemical oxidation, the reaction of the intermediate N-acylated thiazolium cation with primary amines is completed by passage through a heating cell to achieve high conversion in a single pass. The flow mixing regimen circumvented the issue of competing imine formation between the aldehyde and amine substrates, which otherwise prevented formation of the desired product. High yields (71–99%), productivities (up to 2.6 g h–1), and current efficiencies (65–91%) were realized for 19 amides.