657408-07-6

1. Ligand/palladium catalyst for general Suzuki-Miyaura cross-coupling reactions.
2. Ligand/palladium catalyst for the Suzuki-Miyaura coupling of aryltrifluoroborates with aryl chlorides.
3. Ligand/palladium catalyst for the Suzuki-Miyaura reaction of heteroaryl halides and heteroaryl boronic acids and esters.
4. Ligand/palladium catalyst for the Kumada-Corriu cross-coupling reaction.
5. Ligand/palladium catalyst for the borylation of aryl halides with pinacol borane.
6. Suzuki couplings involving amino acids. Synthesis of biaryl derivatives of 4-hydroxyphenyl glycine, tyrosine and tryptophan.
7. Synthesis of substituted adamantylzinc reagents using Mg-insertion in the presence of zinc chloride.
8. Highly efficient catalyst for the palladium-catalyzed Suzuki-Miyura reaction of heteroaryl halides and heteroaryl boronic acids
9. and esters.

694-80-4

151-10-0

16523-54-9

657408-07-6

To a solution of 1,3-dimethoxybenzene (2 mL, 15.30 mmol) in anhydrous THF (35 mL) was slowly added n-butyllithium (nBuLi, 6.2 mL, 15.50 mmol) through a dropping funnel over 5 min at 0 °C. The reaction mixture was stirred at room temperature for 3.5 h. After stirring, 2-bromochlorobenzene (1.6 mL, 13.70 mmol) was added slowly dropwise through a syringe at 0 °C for 30 min. After stirring for 15 min, the reaction mixture was cooled to -78 °C and n-butyllithium (6.20 mL, 15.50 mmol) was again added slowly through a dropping funnel over 5 min. 30 min later, chlorodicyclohexylphosphine (3.03 mL, 13.70 mmol) was added. The reaction mixture was kept at -78 °C for 1 h, during which rapid mechanical stirring was performed. Subsequently, the reaction mixture was warmed to room temperature and the resulting precipitate was filtered through a silica gel sintered disc covered with a cellulose acetate layer and washed with 600 mL of ethyl acetate. The filtrate was concentrated by rotary evaporation and the resulting orange oil was recrystallized in acetone to give white crystalline S-Phos ligand in 36% yield (1.22 g, 2.97 mmol). Melting point: 163-165 °C (literature value 162.0-162.5 °C); Thin layer chromatography (TLC) conditions: ethyl acetate/cyclohexane (10/90), Rf = 0.65; 1H-NMR (CDCl3): δ = 0.99-1.26 (m, 10H, H(Cy)), 1.60-1.77 (m, 12H, H(Cy)), and 3.67 (s, 6H, Me), 6.58 (d, 2H, J = 8.2 Hz, H3' and H5'), 7.15-7.18 (m, 1H, H(Ar)), 7.18-7.42 (m, 3H, H(Ar)), 7.57 (d, 1H, J = 7.4 Hz, H(Ar)) ppm; 13C-NMR (CDCl3): δ = 26.5, 27.3, 27.4, 27.6, 29.0, 29.1, 29.8, 30.1, 33.8, 34.0 (C(Cy)), 55.3 (Cb), 103.1 (Ca), 126.2, 128.2, 128.8 (C3', C4', C5'), 130.9, 131.00, 132.4. 135.8 (C3, C4, C5, C6), 135.8, 136.1, 142.7, 143.1, 157.4 (C2', C6') ppm; IR (KBr): υ = 3000, 2923, 2851, 1588, 1471, 1442, 1428, 1108 cm-1.