Exploration and development of carbazole-based phosphine ligands towards Suzuki-Miyaura cross-coupling and Buchwald-Hartwig amination

Abstract

The research study is focused on the design and synthesis of bulky heterocyclic phosphine ligands. An easily accessible synthesis of a new family of carbazolyl-derived phosphine ligands has been investigated. The substituted carbazoles are synthesized by employing the Fischer indolisation protocol and followed by reduction using Palladium/Charcoal. This carbazole is coupled with iodobromobenzene by ligand-free copper catalyzed C-N bond formation. The ligand scaffold can be made easily without tedious chromatographic purification. The exploration of palladium-catalyzed cross-coupling using carbazole-based phosphine ligands has been demonstrated. With the combination of phosphine ligand and Pd(OAc)₂, a difficult tri-ortho-substituted biaryl synthesis is accomplished. In particular, the catalyst loading down to 0.02 mol% of Pd for non-activated aryl chloride coupling can be achieved. Also, this catalyst system is demonstrated to be effective in low catalyst loading amination of aryl chlorides. The catalyst loading could reach 0.05 mol% Pd in the coupling of 2-chlorotoluene and N-methylaniline.