Rapid catalyst evaluation for Sonogashira coupling in continuous flow

Abstract

Selection of the most appropriate catalyst for Pd-catalyzed Sonogashira coupling often requires time and resources. We applied a continuous flow device for rapid catalyst screening of 4 heterogeneous catalysts over 6 Sonogashira coupling reactions together with longevity estimation. The screening procedure requires only 8 hours. For coupling the alkynes with 4- iodo-anisole Fibrecat types of catalysts showed the highest performance, while when 4-bromo- anisole was applied as an aromatic halide PdCl2(PPh3)2 DVB gave superior results. For phenyl- acetylene and ethynyl-cyclohexene the coupling of the bromo derivative resulted in relatively low conversion as well as selectivity for most of the polymer-bound catalysts. Applying the cheap catalyst 10% Pd/C the coupling reaction could only be achieved with the rather reactive 4-iodo-anisole although with moderate conversion. ©ARKAT-USA, Inc.