Origins of High Catalyst Loading in Copper(I)-Catalysed Ullmann- Goldberg C-N Coupling Reactions

Mechanistic investigation of Ullmann-Golberg reactions using soluble and partially soluble bases led to identification of various pathways for catalyst deactivation through (i) product inhibition with amine products, (ii) byproduct inhibition with inorganic halide salts, and (iii) ligand exchange by soluble carboxylate bases. Reactions using a partially soluble inorganic bases showed variable induction periods, which is responsible for reproducibility issues in these reactons. Surprisingly, more finely milled Cs2CO3 resulted in longer induction period due to higher concentration of deprotonated amine/amide, leading to suppressed catalytic activity. These results have singificant implications on future ligand development for Ullmann-Goldberg reaction, and on the solid form of the inorganic bases as an important variable with mechanistic ramifications in many catalytic reactions.