Metal-free, Mild, and Selective Synthesis of Bis (pyrazolyl)alkanes by Nucleophile-Catalyzed Condensation

(pyrazolyl)alkanes are a prolific class of ligands for catalysis, accessible by the condensation between (pyrazolyl)methanones and carbonyls. In this report, we describe a nucleophile-catalyzed innovation on this condensation that avoids the transition metals, high temperatures, reagent excess, and air-sensitive reagents common among the existing protocols. Significantly, this method accommodates sterically hindered and electronically diverse pyrazoles and aldehydes, applicable for systematic ligand optimization. Furthermore, our scope includes azoles and bridging functional groups previously unreported for this reaction, promising for new heteroscorpionate catalysts. We provide the first direct evidence for an elusive reaction intermediate and characterize the most complete mechanism for this condensation.