Accessing Diverse Phosphorylated 2-Aryl Pyridines: A Strategic Protocol from Pd-PEPPSI to Palladium Acetate Catalysis

Abstract

We evaluated the catalytic performance of our house-made Pd–PEPPSI (Pyridine Enhanced Pre-catalyst Preparation Stabilization and Initiation) complexes in sequential Suzuki–Miyaura (C–C) and oxidative C–P cross-coupling reactions. The targeted transformation involved the reaction of 2-bromopyridine, aryl boronic acids, and alkyl/aryl phosphites to yield dialkyl (2-(pyridin-2-yl)aryl)phosphonates. Pd–PEPPSI systems exhibited excellent efficiency in C–C bond formation under mild conditions, demonstrating broad substrate scope and good functional-group tolerance. In contrast, their application in the subsequent C–P bond formation proved challenging, and no productive phosphorylation was observed. These findings highlight the strong potential of Pd–PEPPSI complexes in C–C bond formation while delineating their limitations in C–P bond construction, thereby guiding the selection of suitable palladium catalysts for diverse C–P bond-forming transformations. We then examined the reaction between 2,6-dibromopyridine and aryl phenyl boronic acid, which successfully gave the 2,6-diarylpyridine product in excellent yields. However, subsequent reaction with dibutyl phosphite did not yield any phosphorylated product.