Uses
Monodentate P-donor ligand.
Used as a phosphitylation reagent for oligonucleotide synthesis.
reaction suitability
reaction type: Buchwald-Hartwig Cross Coupling Reaction
reaction type: Heck Reaction
reaction type: Hiyama Coupling
reaction type: Negishi Coupling
reaction type: Sonogashira Coupling
reaction type: Stille Coupling
reaction type: Suzuki-Miyaura Coupling
reagent type: ligand
Synthesis
4.3.1. Synthesis of tert-butyliminotris(1-pyrrolidinyl)orthophosphine. All operations were carried out under dry argon protection using freshly distilled dry solvents. In a 1L three-necked round-bottomed flask equipped with a PTFE-coated magnetic stirring bar, thermometer, dropping funnel, and argon inlet, freshly distilled pyrrolidine (85.20 g, 1.198 mol) and THF (300 mL) were added, and the mixture was cooled to -40°C. Subsequently, PCl3 (20.05 g, 0.146 mol) was added slowly and dropwise at -40°C in THF (200 mL) solution. After the dropwise addition, the reaction mixture was slowly warmed to room temperature and stirred at room temperature for 18 hours. Upon completion of the reaction, the solvent was removed under vacuum at room temperature and 50 mbar pressure and the solid residue was washed twice with hexane (2 x 100 mL). The hexane layers were combined and concentrated under vacuum at room temperature and 50 mbar pressure to afford tris(1-pyrrolidinyl)phosphine (29.34 g, 0.122 mol) as a colorless liquid. The resulting phosphine was transferred to a 250 mL three-necked round-bottomed flask equipped with a PTFE-coated magnetic stirring bar, a thermometer, a dropping funnel, and an argon inlet, cooled to 5°C, and tert-butyl azide (14.5 g, 0.146 mol) was added dropwise. The reaction mixture was stirred overnight at room temperature and subsequently heated to 85°C for 1 hour and cooled to room temperature. The volatiles were removed at 50 mbar pressure for 30 min. BaO (1.0 g) was added and the reaction mixture was heated at 140°C for 40 hours. Finally, the target product P1-base (29.1 g, 64% yield) was obtained by vacuum distillation over BaO.
References
[1] Journal of the American Chemical Society, 2003, vol. 125, # 4, p. 940 - 950
[2] European Journal of Organic Chemistry, 2013, # 9, p. 1811 - 1823
[3] Journal of Organic Chemistry, 1994, vol. 59, # 6, p. 1257 - 1263
[4] Journal of the American Chemical Society, 1995, vol. 117, # 29, p. 7696 - 7710
[5] Tetrahedron, 2011, vol. 67, # 30, p. 5382 - 5388
