Sejal Patel, Nello Mainolfi, and co-workers, Novartis Institutes for Biomedical Research, Massachusetts, USA, have developed a copper tube flow reactor (CTFR) which produced yields of over 90 % for almost all of the 22 coupling reactions examined.

The reactor was made of a coil of copper tubing which was wound around an open mesh support. When the coil was inserted into a metal jacket, it could be safely heated to 250 °C. The heated CTFR was shown to acts as the catalytic source of copper for Ullmann condensations, Sonogashira couplings, and decarboxylation reactions without the need for additional catalysts, ligands or reagents.

Flow synthesis offers several benefits over batch synthesis including efficient mixing, controlled reaction parameters, increased automation, the ability to perform reactions at high temperatures and high pressures, and ease of scale-up.

• Continuous Flow Coupling and Decarboxylation Reactions Promoted by Copper Tubing
  Y. Zhang, T. F. Jamison, S. Patel, N. Mainolfi,
  Org. Lett. 2010.
  DOI: 10.1021/ol1026848