To further improve the system the reaction was run in 2-MeTHF, Pd2(dba)3 replaced Pd(OAc)2, and K3PO4 was chosen as the base instead of Cs2CO3. Combining these benefits allowed catalyst loading to be reduced to 1.5 mol% (Figure ). Still, given the expense of palladium an option to further minimize consumption was desired. Subsequent screening identified Xantphos as a ligand imparting high catalyst activity. 0.25-0.5 mol% catalyst loading effectively promoted the reaction, thus essentially rendering the cost of palladium in this step negligible (Figure ). Unfortunately, the reaction showed sensitivity to scaling at these levels, and the initial results obtained at small scale did not reproduce when performed in jacketed vessels with overhead stirrers. Reaction kinetics revealed strong dependence on concentration of potassium phosphate and prolinol, suggesting that formation of a transmetallating agent might be rate limiting. Microscopy showed that the phosphate surface area was greatly increased by grinding action of the stir-bar. Comparing commercial phosphate with ground phosphate showed the high-surface area phosphate was considerably more active. Reactions were run on a heated shaker block to eliminate mixing and grinding effects (Figure ). Wet-milling the hygroscopic phosphate in 2-MeTHF similarly increased reaction rate and provided a kilogram scale approach to reproduce this effect and enhance reaction kinetics at low catalyst loading (Figure ). Step 4: