Flow-to-Flow Technology: Amide Formation in the Absence of Traditional Coupling Reagents Using DPDTC

Reported herein is the use of a recyclable coupling agent, 2,2'-dipyridyldithiocarbonate (DPDTC), that generates isolable thioesters in a plug flow reactor (PFR). If not isolated, thioesters can be reintroduced directly into the PFR, along with amines, to generate amides in a "flow-to-flow" sense. Both electron-rich and -poor aromatic acids, as well as sterically hindered aliphatic acids, are efficiently coupled with a variety of amines, including the formation of Weinreb amides and peptides, in high yields.