Novel Thioether Ancillary Ligands: a Next Generation of Catalysts for Rapid and Efficient Palladium-Catalyzed Fujiwara-Moritani Reactions of Electron-Rich Heterocycles

Abstract

Cross Dehydrogenative Coupling reactions represent a particularly green, atom economical, and efficient alternative to C-C bond formation when compared to traditional metal catalyzed coupling reactions. However, these reactions typically suffer from the need for high catalyst loadings, high temperatures, stoichiometric oxidants, long reaction times, selectivity issues and excess or solvent amounts of reagent. All of these issues limit the synthetic practicality of these reactions especially at larger scales. This work addresses several of the issues of CDC reactions by the use of an underutilized class of ancillary ligand—thioethers. In this work, thioether ligands are shown to facilitate the palladium-catalyzed Fujiwara-Moritani reaction of electron-rich heterocycles and electron-deficient olefins. Through extensive ligand screening, it was determined that monodentate electron-rich aryl-alkyl thioethers lead to the most active catalysts. This new catalyst system allows for remarkably fast reactions, high turnover numbers, the use of arene as the limiting reagent, and the use of molecular oxygen as the terminal oxidant. Finally, mechanistic studies indicate that the origin of the dramatic rate enhancement observed for this reaction is turnover-limiting C-H activation by a cationic palladium species that is stabilized by electron-rich thioether ligands following loss of acetate ligand.