Accessing diverse phosphorylated 2-aryl pyridines: a strategic protocol from Pd-PEPPSI to palladium acetate catalysis

Abstract

We evaluated the catalytic performance of our home-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. The 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. The final products were characterized by ¹H, ¹³C and ³¹P NMR spectroscopy, and a few of them were confirmed by high-resolution mass spectrometry (HRMS) methods.