Additive effects on palladium-catalyzed deprotonative-cross-coupling processes (DCCP) of sp³C–H bonds in diarylmethanes

Abstract

Palladium-catalyzed cross-coupling reactions have become one of the most useful tools in modern organic chemistry. Current methods to achieve direct functionalization of sp3 C–H bonds of arenes and heteroarenes often employ substrates with appropriately placed directing groups to enable reactivity. Examples of intermolecular arylation methods of weakly acidic sp3 C–H bonds in the absence of directing groups, however, are still limited. We describe herein a study on the use of additives in Pd-catalyzed deprotonative-cross-coupling processes (DCCP) of sp3 C–H bonds of diarylmethanes with aryl bromides at room temperature. These studies resulted in development of four new efficient Pd-catalyzed DCCP using additives that enabled the generation of a range of sterically and electronically diverse aryl- and heteroaryl containing triarylmethanes in good to excellent yields. Additive identification and optimization of all reaction conditions (additive loading, solvent and temperature) were performed using high-throughput experimentation (HTE). The approach outlined herein is expected to be generalizable to other C–H functionalization reactions involving the deprotonation of weakly acidic C–H bonds.