Design of highly efficient catalyst for transition-metal catalyzed cross-coupling processes

Abstract

A new family of monodentate phosphine ligands based on the use of indole as the ligand template were designed and synthesized. These ligand templates are inexpensive, readily available and highly diversified. This family of ligand scaffold could be easily prepared and diversified from inexpensive arylhydrazines and substituted acetophenones by straightforward Fischer-Indolization. Two classes of ligands, N-P bound amino-phosphine ligands and C-P bound phosphine ligands, were synthesized and derivatized by using a modular approach. The amino-phosphine ligands had exhibited exceedingly high activity in the Suzuki-Miyaura coupling of aryl chlorides. The sterically hindered and deactivated aryl chlorides with arylboronic acid could cross-coupling to afford the biaryl products in excellent yields. The catalyst bearing the amino-phosphine ligand could achieve very low catalyst loading in the Suzuki coupling reaction. The Pd-C-P type indolyl phosphine complexes in which the phosphine group (-PPh₂ or -PCy₂) was attached at the C-3 position were also highly active towards the Suzuki-Miyaura coupling of aryl chlorides. The Pd/CPPh o-Andole-phos and Pd/CPPh α -Nadole-phos could catalyze the tetra-ortho-substituted biaryl coupling reaction. The Pd-C-P type indolyl phosphine complexes in which the phosphine group was attached at the ortho position of the bottom ring were highly active towards coupling reactions of aryl tosylates and previously unexplored aryl mesylates. This Pd/CM-Phos catalytic systems showed good to excellent catalytic activity in the Suzuki coupling reaction, amination reaction, and Hiyama coupling reaction of the aryl tosylates and/or aryl mesylates.