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

Org Lett. 2016 Mar 4;18(5):1198-201. doi: 10.1021/acs.orglett.6b00339. Epub 2016 Feb 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't