The reaction of 1a mediated by Pd(OAc)2/dppe (1:1) was monitored by GC analysis, with the consumption of 1a assessed at 80 °C in DMF using both a cold and hot pre-activation protocol (Scheme 3B). When the reaction mixture was heated from room temperature (ca. 23 °C), an induction period of ca. 10 minutes was observed, with the reaction nearing completion (94% conversion) after 2.5 h. However, when the precatalyst mixture in DMF was heated to 80 °C for 2 min prior to addition of 1a, the induction period was shortened (<2 min), with the reaction reaching completion within 2 h. The difference in the precatalyst activation process highlights the impact on the overall reaction time, with the pre-heating method being more effective for quantitative conversion of 1a to products. Independent reactions between Pd(OAc)2 and dppe showed that Pd 0 (dppe)n species (n = 1 or 2) were formed (vide infra). Next, a robust LC-MS method for profiling the reactions from the HTE campaign (in batch mode) was developed. Generally, we observed (by chromatographic and spectroscopic methods) that many products were formed in reaction mixtures accompanying 2a, 2a-d5 and 2b, the majority of which were formed in low amounts but in significant enough quantity to warrant comprehensive profiling. This would fulfill our aspirations to gain greater understanding of this complex reaction network. Characterization of these species was achieved by LC-MS, GC-MS, flash column chromatography and preparative HPLC on the crude reaction mixtures and comparing the spectroscopic and chromatographic data with those of authentic product samples (see supporting information for full details). Through this approach we identified a total of 17 side-products and by-products of interest in the LC-MS reaction profiles (Figure ).