Additive effects on palladium-catalyzed deprotonative-cross-coupling processes (DCCP) of sp3 C–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.