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

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

Palladium-Catalyzed Direct C–H Arylation of 3‑(Methylsulfinyl)thiophenes

A palladium-catalyzed direct arylation of (3-thiophene)­S­(O)­Me derivatives has been developed. This protocol is effective for the selective synthesis of 2-arylated and 2,5-diarylated sulfinylthiophene derivatives with as low as 0.5 mol % catalyst loading. Various functional groups are well tolerated. A method to install two different aryl groups on 3-(methylsulfinyl)­thiophenes is also introduced

Positional Selectivity in C–H Functionalizations of 2‑Benzylfurans with Bimetallic Catalysts

Metal-catalyzed carbon–carbon bond-forming reactions are a mainstay in the synthesis of pharmaceutical agents. A long-standing problem plaguing the field of transition metal catalyzed C–H functionalization chemistry is control of selectivity among inequivalent C–H bonds in organic reactants. Herein we advance an approach to direct site selectivity in the arylation of 2-benzylfurans founded on the idea that modulation of cooperativity in bimetallic catalysts can enable navigation of selectivity. The bimetallic catalysts introduced herein exert a high degree of control, leading to divergent site-selective arylation reactions of both sp² and sp³ C–H bonds of 2-benzylfurans. It is proposed that the selectivity is governed by cation−π interactions, which can be modulated by choice of base and accompanying additives [MN­(SiMe₃)₂, M = K or Li·12-crown-4]

NiXantphos: A Deprotonatable Ligand for Room-Temperature Palladium-Catalyzed Cross-Couplings of Aryl Chlorides

Although the past 15 years have witnessed the development of sterically bulky and electron-rich alkylphosphine ligands for palladium-catalyzed cross-couplings with aryl chlorides, examples of palladium catalysts based on either <i>triarylphosphine</i> or <i>bidentate phosphine</i> ligands for efficient <i>room temperature</i> cross-coupling reactions with unactivated aryl chlorides are rare. Herein we report a palladium catalyst based on NiXantphos, a <i>deprotonatable chelating aryldiphosphine</i> ligand, to oxidatively add unactivated aryl chlorides at room temperature. Surprisingly, comparison of an extensive array of ligands revealed that under the basic reaction conditions the resultant heterobimetallic Pd–NiXantphos catalyst system outperformed all the other mono- and bidentate ligands in a deprotonative cross-coupling process (DCCP) with aryl chlorides. The DCCP with aryl chlorides affords a variety of triarylmethane products, a class of compounds with various applications and interesting biological activity. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of aryl chloride substrates bearing heteroaryl groups and sensitive functional groups that are known to undergo 1,2-addition, aldol reaction, and <i>O</i>-, <i>N</i>-, enolate-α-, and C­(sp²)–H arylations. The advantages and importance of the Pd–NiXantphos catalyst system outlined herein make it a valuable contribution for applications in Pd-catalyzed arylation reactions with aryl chlorides