A New Catalytic System for Ru-Catalyzed C–H Arylation Reactions and Its Application in the Practical Syntheses of Pharmaceutical Agents

Abstract

Biaryls are a significant structural motif found in valuable compounds in materials and the life sciences. Currently, the most reliable and widely used method to synthesize biaryls is through the use of cross-coupling reactions. However, cross-coupling reactions require stoichiometric amounts of reactive organometallics, such as boronic acids, Grignard reagents, or zinc reagents (C-Met; Met = B, Mg, Zn), to enable sp2–sp2 carbon–carbon bond formation. This has generated a large amount of toxic metal waste, some of which is difficult to handle. In the meantime, C–H arylation has aroused a keen interest in the synthesis of biaryls because of its high atom economy. Carbon–carbon bond formation takes place at an unactivated C–H bond in the presence of a transition metal catalyst. Despite such conceptually attractive features, most of the reported protocols require high catalyst loading and often suffer from a lack of reproducibility. During our process development of angiotensin II receptor blockers (ARBs) th...