Synthesis and study of ligands for Pd-catalyzed C-O and C-N coupling

Abstract

A new ligand, AdBrettPhos, was synthesized and its use, along with tBuBrettPhos, in C-O coupling reactions at low temperatures was investigated. Using Pd catalysts containing these ligands, electron-neutral aryl bromides were coupled with phenols at room temperature for the first time. A variety of electron-deficient aryl halides and phenols were also coupled at moderate temperatures in good yields. In order to probe how the structural features of the ligand affect the catalytic activity of Pd catalysts containing dialkylbiarylphosphines, a series of novel ligands was synthesized and their utility in Pd-catalyzed C-N couplings was investigated. All of these ligands provided competent catalysts for the cross-coupling reactions of aryl halides with primary alkyl or aryl amines. However, in general these catalysts cannot match the rates and low catalyst loadings achieved by BrettPhos-supported Pd-catalysts, with the exception of L8, which was shown to be superior to BrettPhos in terms of rate and yield for the coupling of methylamine. The high selectivity for monoarylation of primary amines exhibited by these catalysts indicates that the methoxy substituent ortho to phosphorous plays an important role in regulating this selectivity.