Nickel as a Competitive Drop-In Alternative to Palladium in Thermal C−O Cross-Couplings of Aliphatic Alcohols with Heteroaryl Halides: A High-Throughput Experimentation Study

Virscidian's Analytical Studio software was used to analyze LC–MS data from a high-throughput experimentation campaign comparing nickel and palladium catalysts for C–O cross-coupling. Across multiple 96-well screens, researchers evaluated catalyst, base, solvent, and substrate combinations and used LC–MS response relative to an internal standard to identify the highest-performing reaction conditions. The study showed that selected DalPhos-ligated nickel precatalysts can serve as competitive, and for some tertiary alcohol couplings, superior, alternatives to established palladium catalysts. The work highlights the value of efficient, consistent analytical data processing for turning complex HTE experiments into actionable reaction-development decisions.