Push button, automated flow synthesis of biaryls and stilbenes using palladium-catalysed cross-coupling reactions

A ligand-free, palladium-based heterogeneous nanocatalyst supported on TiO₂ was synthesised with the aid of wet impregnation method and incorporated into an automated continuous flow system for the synthesis of pharmaceutically relevant biaryls and stilbenes via Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions. With the use of 21.2 mg of palladium acetate on 1 g of TiO₂, the catalyst was prepared and characterised, using BET, FTIR, XRD, SEM, TEM, and EDX, which showed a high distribution and revealed the stability of the palladium nanoparticles. Reactions were conducted using 1.0 mmol of substrate, 1.2 mmol of coupling partner, 2.0 mmol of base, and 200 mg of catalyst under a 35-min residence time. In the Mizoroki-Heck reaction, DMF was used as the solvent, and an optimised temperature of 130 °C yielded up to 90 % conversion. In contrast, studies on base and solvent effects indicated that triethylamine and potassium carbonate provided superior reaction performance. Catalyst loading experiments demonstrated that the loading of 3.0 mol% of Pd/TiO₂ is optimal, as lower amounts resulted in reduced conversion and higher loadings. Notably, the reaction selectively produced Z-stilbene, contrary to the common formation of the trans isomer in similar processes. This methodology offers a greener, faster, and more reproducible approach for on-demand synthesis in pharmaceutical manufacturing.

• Onisuru, O
• Alimi, O
• Fapojuwo, D
• Oseghale, C
• Meijboom, R

• Department of Chemical Sciences, University of Johannesburg, P.O. Box 524, Auckland Park, Johannesburg 2006, South Africa

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