A concise overview of our optimization is summarized in Figure . Initial conditions for palladium-catalyzed aryl halide reductive cross-coupling employed a heterogenous catalyst, palladium black. In the best-case scenario, the coupling of 2bromo-6-methylpyridine 1a with 4-iodoanisole 2a, the product of reductive cross-coupling 3a was formed in 55% yield. Reproducibility was an issue with this heterogenous catalyst. The requirement of Bu4NI led us to evaluate the anionic palladium complexes [PdX3(DMSO)][NBu4] (X = Cl, Br); 17 however, rather high temperatures were required and the yield of 3a did not improve. We sought to address key limitations of the initially developed catalyst systems via exploration of experimental parameters using HTE. Specifically, a "tunable" homogenous palladium catalyst that operates with greater efficiency at lower temperature and lower loadings of Bu4NI was sought. In short, after three rounds of HTE in 96-well plates (See Supporting Information), it was found that [Pd(π-C4H7)(P t Bu3)Cl] (5 mol%), Bu4NI (20 mol%) in dioxane:H2O (9:1, 0.2 M) enabled formation of 3a in 73% yield; however, high temperature (130 ⁰C) was still required. Application of these conditions at a lower temperature (100 ⁰C) led to formation of 3a in 44% yield.