Safe Palladium-Catalyzed Cross-Couplings with Microwave Heating Using Continuous-Flow Silicon Carbide Reactors

Herein we present a 200 mm X 3 mm emptyset(i) silicon carbide (SiC) tube reactor for use in a commercially available microwave heated continuous-flow system. The SiC flow reactor enables palladium(0)-catalyzed reactions that, due to precipitation and subsequent hot spot formation, often followed by reactor failure, are unsuitable to conduct in standard microwave-transparent borosilicate glass reactors. We report continuous-flow protocols for the MizorokiHeck reaction (10 examples, 8186% yield) as well as the SuzukiMiyaura cross-coupling (14 examples, 7087% yield), showing the utility of the SiC reactor. Furthermore, we performed a scale-out of the NSAID biphenylacetic acid, achieving outputs of 14 mmol/h of the SuzukiMiyaura reaction, and a 72% overall yield over three steps. The SiC reactor enabled fast and efficient temperature control, high robustness, and easy maintenance.