Si-Gly-CD-PdNPs as a hybrid heterogeneous catalyst for environmentally friendly continuous flow Sonogashira cross-coupling

We have reported a waste-minimized protocol for the Sonogashira cross-coupling exploiting the safe use of a CPME/water azeotropic mixture and the utilization of a heterogeneous hybrid palladium catalyst supported onto a silica/β-cyclodextrin matrix in continuous flow. The use of the aq CPME azeotrope has proven to be crucial to enhance the catalyst performance including very low metal leaching. In addition, we have also completed the flow protocol by setting a downstream in-line liquid/liquid separation that allows the continuous recovery and reuse of the CPME fraction leading to consistent waste reduction. Finally, E-factor distribution and safety/hazard analysis have been performed highlighting the chemical and environmental efficiency of our protocol.