Table of Contents 1. Characterization data of carbazolyl phosphine ligands L2-L4…………………………………. S22. X-ray data of L4 ……………………………………………………………………………………………………… S73. X-ray data of product 6 in Scheme 4………………………………………………………………………… S17 4. 1 H, 13 C and 31 P NMR spectra …………………………………………………………………………………… S28 References………………………………………………………………………………………………………………. S57Supporting Information S2 Characterization data of carbazolyl phosphine ligands L2-L4 General Procedures for Ligand-free Cu-catalyzed amination:Substituted carbazole (40 mmol), CuI (40 mmol, 7.62 g), K2CO3 (80 mmol, 11.0 g) andTeflon-coated magnetic stirrer bar were charged to a two-necked round bottom flask equipped with a condenser and fitted with a septum. The system was carefully evacuated and backfilled with nitrogen (3 cycles). 1,2-Dibromobenzene (80 mmol, 9.65 mL) and distilled dry xylene (130 mL) were added by syringe via septum. The reaction mixture was allowed to reflux in a heating mantle/ preheated oil bath (185 ℃) for 3-7 days. After completion of reaction, the solution was filtered through Celite to remove the copper powder and the xylene was removed by distillation under high vacuum. The crude products (ligand precursor) were purified by flash column chromatography on silica gel (230-400 mesh) to afford the product as a white solid. General Procedures for nucleophilic phosphination:The ligand precursor obtained (5 mmol) was then dissolved in freshly distilled THF (25 mL) at room temperature under nitrogen. The solution was cooled to -78 ℃ in a dry ice/ acetone bath. Titrated n-BuLi (5.5 mmol) was added dropwise with a syringe, and the reaction mixture was stirred for 30 min at -78 ℃. Chlorodicyclohexylphosphine (6 mmol, 1.32 mL) was then added dropwise to the reaction mixture with a syringe. The reaction mixture was warmed to room temperature and stirred for 12 h. The solvent was then removed under reduced pressure. Methanol (10 mL) was added to the residue, and the Supporting Information S3 mixture was stirred at 1250 rpm for 10 min. The white solid product was successively filtered and washed with cold methanol. The white solid was collected and dried over vacuum to afford the carbazolyl-based phosphine ligands. 9-(2-(Dicyclohexylphosphino)phenyl)-3,6-dimethoxy-9H-carbazole (L2) Sodium (200 mmol, 4.6 g) was added in methanol (27 mL) slowly. When all sodium was completely dissolved, distilled dry DMF (107 mL), CuI (40 mmol, 7.62 g) and 3,6dibromocarbazole (10 mmol, 3.25 g) were added. The reaction mixture was allowed to reflux in a preheated oil bath (120 ℃) under nitrogen for 3 hours. After the completion of reaction, ethyl acetate (400 mL) was added and the solution was filtered through Celite to remove the copper powder. The organic layer was extracted with EtOAc, washed with brine. The crude product was purified by flash column chromatography to obtain 3,6dimethoxy-9H-carbazole as yellow solid (62%, 1.41 g). 1 Hexane: EtOAc = 9:1, Rf = 0.23; 1 H NMR (500 MHz, CDCl3) δ 7.77 (s, 1H), 7.50-7.49 (d, J = 2.0 Hz, 2H), 7.32 -7.30 (d, J = 9.0 Hz, 2H)...

Phosphine ligands embodying a carbazolyl motif have been found to be successful in many palladium-catalyzed biaryl syntheses and direct C–H bond arylation processes. Here, a practical scaled-up synthesis of a series of carbazolyl-derived phosphine ligands, the PhenCarPhos series, is described. The original protocol for accessing the target ligand skeleton via aromatic C–N bond formation is limited by the use of a substoichiometric amount of copper salt and diamine catalysts, which both add cost and generate purification problems (significant amounts of side products and copper residues). In order to develop a more attractive and scalable synthetic pathway, a simple nucleophilic substitution method was attempted involving simple heating of 1-bromo-2-fluorobenzene, a carbazole derivative, and KOH in DMF without inert atmosphere protection. This route enables the large-scale synthesis of the desired ligand skeletons and minimizes the association of inseparable reduction side products. Particular examples of the use of these ligands in Pd-catalyzed sterically hindered arylation processes are also shown.