Heterogeneous cross-coupling catalysts typically lose some portion of activity to metal leaching between different runs as a result of the solution-phase catalytic cycle (see above), and hence can only be recycled a finite number of times.
Multiple groups have pointed out that the need for recycling is obviated at extremely high turnover and low catalyst loading, since in these cases the catalyst cost is negligible relative to the cost of other reaction components. As a result, for most cross-coupling reactions, in which heterogeneous catalysts generally require higher loadings than equivalent homogeneous ones, the benefits of heterogeneous catalysts afforded by the greater ease of recycling may be outweighed by the disadvantages – higher catalyst loadings, and the additional process costs. Additionally, when catalyst loadings are lower than 10 ppm – the regulatory limit for several metals including Pd in pharmaceutical APIs – separation of the metal following the reaction does not even need to be performed. This nullifies another of the commonly perceived advantages of heterogeneous catalysts over their homogeneous counterparts.