(R)-2,2′-BINAPHTHOYL-(S,S)-DI(1-PHENYLETHYL) AMINOPHOSPHINE. SCALABLE PROTOCOLS FOR THE SYNTHESES OF PHOSPHORAMIDITE (FERINGA) LIGANDS

Caution! Decomposition of excess PCl3 (step A) should be carried out carefully in a fume-hood because hydrogen chloride is evolved in the highly exothermic hydrolysis reaction. A. (R)-(−)-(1,1′-Binaphthalene-2,2′-dioxy)chlorophosphine [1]2 A 250-mL, single-necked round-bottomed flask, equipped with a magnetic stirring bar, a reflux condenser, a three-way flow-controlled stopcock is flame-dried and purged with nitrogen. All joints are greased. The nitrogen outlet is connected to a gas scrubber trap (Note 1). The flask is charged with (R)-(+)-1,1′-bi(2-naphthol) (7.0 g, 24.5 mmol) (Note 2) and phosphorus trichloride (20.5 mL, 32.3 g, 235 mmol, 9.6 equiv) (Note 3) followed by 1-methyl-2-pyrrolidinone (20 μL, 0.2 mmol, 0.008 equiv) (Note 4). The flask is placed in an oil bath preheated to 92 °C. The solid dissolves within 5 min. The flask is swirled to dissolve the solid on the side. During this period, HCl evolves rapidly and the solution becomes yellow. The solution is kept at reflux for 10 min, then the oil bath is removed and the reaction mixture is allowed to cool to ambient temperature. The remaining phosphorus trichloride and HCl are removed under reduced pressure (7 mmHg) (Note 5) for 2 h, leaving a foamy wax. After venting the flask with nitrogen, diethyl ether (30 mL) (Note 6) is added to dissolve the solid. The solven