Title : Palladium catalyzed beta C(sp3) H arylation of weinreb amides via acidic ligands
Abstract:
Pd-catalyzed C−H functionalization of weak-coordinating substrates remained challenging and limited.1 Traditionally, nitrogen-based, strong coordinating groups have been most widely used as directing groups for C(sp3)−H activation, presumably because of the facile cyclometalation process that forms stable palladacycle intermediates. On the other hand, utilizing oxygen-based neutral-coordinating groups such as Weinreb amides to direct C(sp3)−H activation remains a significant challenge. Recently, Yu and coworkers reported the discovery of 3-pyridinesulfonic acid as a uniquely enabling ligand for Pd catalysed β?C(sp3)−H arylation of Weinreb amide.2 In the course of our investigation in regioselective arylation of arenes, we disclosed that such a process can also be promoted by other inexpensive acidic commercially available ligands in a highly efficient mode. These acidic ligands would provide a suitable cationic Pd (II) center without binding nitrogen, in some cases even active Pd(I) species, for the efficient Csp3-H activation. It also enables rapid domino synthesis of ketoamide. Remarkably, such process allows late stage functionalization of peptides.
