(200u) Plasmonic Nanocatalysts for Continuous Synthesis of Drug Substances: An Example of Visible-Light Mediated Cross Coupling Reactions

Approximately 25% of all the reactions performed in the pharmaceutical industry consist of cross-coupling reactions. The cross-couplings have been traditionally carried out by homogeneous palladium (Pd) catalyzed batch processes. The National Science and Technology Council (NSTC) has recently identified the continuous manufacturing of pharmaceuticals as one of five manufacturing areas of emerging priority in the USA, revealing that continuous manufacturing of pharmaceuticals has the potential to reduce manufacturing cost by up to 40-50%. Given these advantages, in recent years, metal nanoparticle catalyzed cross-couplings have been of great interest since they can be used as a platform to switch cross-couplings from traditionally used batch mode to continuous flow mode. Additionally, heterogeneous metal nanocatalysts can be immobilized on a rigid support in the form of a packed-bed reactor, and therefore, can avoid the need for subsequent difficult steps to separate the catalyst and product.

In this contribution, we show that heterogeneous plasmonic metal nanocatalysts build on silver (Ag), copper (Cu) and gold (Au) can be used as alternate catalysts to drive cross couplings. Specifically, we demonstrate that visible light can be used as a powerful tool to make plasmonic metal nanocatalysts as efficient photo-catalysts with activity and stability superior to that of traditionally used homogeneous Pd based catalysts. These plasmonic metal nanocatalysts can be used to design efficient cross-coupling flow processes to produce drug substances.