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

Abstract

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 triarylphosphine or bidentate phosphine ligands for efficient room temperature cross-coupling reactions with unactivated aryl chlorides are rare. Herein we report a palladium catalyst based on NiXantphos, a deprotonatable chelating aryldiphosphine 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 O-, N-, 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.

Recent Advances in the Synthesis of Triarylmethanes by Transition Metal Catalysis

“…26 LiN(SiMe 3 ) 2 was found to be an effective base because it can generate benzyllithium intermediates by deprotonation of benzylic protons activated by η 6 -coordination of the arene to Cr(CO) 3 . After Pd-catalyzed coupling of this deprotonated species, the resulting triarylmethane−Cr(CO) 3 complex was decomposed by exposure to air and light to give the triarylmethane in excellent yield.…”

Cerium(III) and Uranium(IV) Complexes of the 2-Fluorophenyl Trimethylsilyl Amide Ligand: C–F → Ln/An Interactions that Modulate the Coordination Spheres of f-Block Elements

“…This value is significant given that a small difference of 0.08 was found for natural charges on phosphine atoms between trialkyl phosphine and triphenyl phosphine using the the same computational method. 55 To test our hypothesis of stronger C−F → Ln/An interactions, the homoleptic model complex Ce[N(SiMe 3 )-(C 6 H 4 F)] 3 (1-F 1 ) was synthesized and compared to previously reported Ce[N(SiMe 3 )(C 6 F 5 )] 3 (1-F 5 ). 32 Stirring an n-pentane solution of Ce[N(SiMe 3 ) 2 ] 3 with HN(SiMe 3 )(C 6 H 4 F) led to a white precipitate of 1-F 1 during 6 d in 68% yield.…”

Palladium-Catalyzed Cross-Coupling of 2-Aryl-1,3-dithianes

“…It has been shown that under the basic reaction conditions, NiXantphos is likely deprotonated, leading to a very electronrich palladium center. 21 Additionally, van Leeuwen and coworkers disclosed that NiXantphos has both a larger bite angle and is more flexible than Xantphos. 22 Investigations are ongoing in our lab to try to ascertain which of these phenomena, if either, leads to the observed difference in reactivity.…”