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Palladium-Catalyzed C(sp3)–H Arylation of Diarylmethanes at Room Temperature: Synthesis of Triarylmethanes via Deprotonative-Cross-Coupling Processes

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journal contribution
posted on 22.08.2012, 00:00 by Jiadi Zhang, Ana Bellomo, Andrea D. Creamer, Spencer D. Dreher, Patrick J. Walsh
Although metal-catalyzed direct arylation reactions of non- or weakly acidic C–H bonds have recently received much attention, chemists have relied heavily on substrates with appropriately placed directing groups to steer reactivity. To date, examples of intermolecular arylation of unactivated C­(sp3)–H bonds in the absence of a directing group remain scarce. We report herein the first general, high-yielding, and scalable method for palladium-catalyzed C­(sp3)–H arylation of simple diarylmethane derivatives with aryl bromides at room temperature. This method facilitates access to a variety of sterically and electronically diverse hetero- and nonheteroaryl-containing triarylmethanes, a class of compounds with various applications and interesting biological activity. Key to the success of this approach is an in situ metalation of the substrate via C–H deprotonation under catalytic cross-coupling conditions, which is referred to as a deprotonative-cross-coupling process (DCCP). Base and catalyst identification were performed by high-throughput experimentation (HTE) and led to a unique base/catalyst combination [KN­(SiMe3)2/Pd–NiXantphos] that proved to efficiently promote the room-temperature DCCP of diarylmethanes. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of substrates that are known to undergo O-, N-, enolate-, and C­(sp2)–H arylation.