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 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.