For batch cross-couplings which use immobilized Pd, the concentration of solution-phase Pd increases dramatically when the reaction commences (as Pd is transferred out of the solid phase), and has decreased dramatically by the time full conversion has been achieved (by readsorption or precipitation onto the solid support). Such a kinetic profile matches the processing requirements of a batch process – although some amount of metal remains in solution post-reaction, the supported Pd catalyst can usually be recycled several times, despite the limitations described above.
In contrast, continuous flow systems do not allow for effective metal redeposition on the solid support; the reaction stream will transport the Pd through the support due to continuous metal leaching/readsorption (Figure 4). Cumulative periods of operation inevitably result in significant metal leaching from the flow system, depleting the supported catalyst's activity and giving low recyclability, with – typically – no particular benefit for reactivity.
In principle, it is possible for the metal leaching inherent to continuous flow cross-coupling to be avoided. Plucinkski and coworkers developed a continuous Mizoroki-Heck and hydrogenation sequence consisting of two separated packed-bed reactors containing Pd/C. Because the Pd/C-catalyzed hydrogenation proceeds via a heterogeneous mechanism, metal leaching due to the second hydrogenation step is minimal, and Pd leached from the first part of the reactor during the Heck coupling can be recaptured by the second packed bed during the hydrogenation. By cycling the direction of flow between forward and reverse, catalytic activity could be maintained over two consecutive experiments, although a greater number of cycles would be desirable in order to vindicate this strategy for increasing turnover in solid-supported flow catalysts for cross-coupling.