Preparation of (R)-3,3′-bis(3,5-bistrifluoromethoxyphenyl)-1,1′-bis-(2-naphthol)phosphate_Industrial additives

Background and overview^[1]

(R)-3,3′-Bis(3,5-bistrifluoromethoxyphenyl)-1,1′-bi-(2-naphthol)phosphate is a chiral binaphthyl Phenol-phosphoric acid derivatives can be used as catalysts to carry out asymmetric synthesis reactions such as asymmetric Mannich-type reactions, asymmetric hydrogenation phosphorylation reactions, and asymmetric aza-Diels-Adel reactions.

Preparation^[1]

1) Synthesis of (R)-3,3′-bis(3,5-bistrifluoromethoxyphenyl)-1,1′-bi-(2-naphthol)

In a dried three-neck (100ml) eggplant-shaped flask, add Pd(PPh₃)₄ (0.15mM, 0.06eq) in sequence under a nitrogen atmosphere , dimethoxyethane (15ml), 3,5-bis(trifluoromethyl)bromobenzene (7.54mM, 3.0eq), stir for 10 minutes. Subsequently, (R)-3,3′-bis(dihydroxyborane)-2,2′-dimethoxy-1,1′-binaphthyl (2.56mM) diluted with ethanol and 2 equivalents ( N) sodium carbonate aqueous solution (7.6mM, 3.0eq), heated to reflux for 18.5 hours. Subsequently, it was cooled to room temperature, and dimethoxyethane was distilled off under reduced pressure. Then, it was dissolved with dichloromethane and 1 equivalent of hydrochloric acid, and extracted three times with dichloromethane. The combined dichloromethane extracts were washed with 1 equivalent of hydrochloric acid and brine in sequence, and dried over anhydrous sodium sulfate. After drying, filtration was performed, and the methoxy group was removed from the substance obtained by concentrating the filtrate. The deprotected substance was purified by column chromatography to obtain (R)-3,3′-bis(3,5-bistrifluoromethoxyphenyl)-1,1′-bi-(2-naphthalene) Phenol) (1.4g, 2.01mM, 79%).

IR(CHCl₃): 3522, 1622, 1597, 1502, 1474, 1462, 1427, 1377, 1358, 1335, 1281, 1236, 1182, 1140, 1036, 989, 897, 845cm^-1.

¹H-NMR (MHz, CDCl₃)δ=8.24(s, 4H), 8.12(s, 2H), 8.00(d, 2H, J =7.9Hz), 7.91(s, 2H), 7.50-7.40(m, 4H), 7.24-7.22(m, 2H), 5.38(s, 2H).

¹³C-NMR (100MHz, CDCl₃)δ=149.86, 139.47, 133.24, 132.35, 132.09, 131.76, 131.42, 131.09, 129.85, 129.46, 128.90 , 128.67, 127.71, 127.49, 125.21, 124.78, 123.97, 122.06, 121.33, 119.35, 111.75.

2) Synthesis of (R)-3,3′-bis(3,5-bistrifluoromethoxyphenyl)-1,1′-bis-(2-naphthol)phosphate

Add (R)-3,3′-bis(3,5-bistrifluoromethoxyphenyl)-1,1′-bis-(2-naphthol)( 1.91 mmol) and pyridine (7.8 mmol), phosphorus oxychloride (2.69 mmol) was added dropwise thereto over 7 minutes at room temperature, and the mixture was further stirred for 2 hours. Then heat to reflux for 1 hour. The reaction solution was cooled to room temperature, distilled water (1.6 ml) was added dropwise, and the mixture was heated to reflux for 1.5 hours. Subsequently, the mixture was cooled to room temperature, pyridine was removed by distillation under reduced pressure, 6M hydrochloric acid (15 ml) was added dropwise, and the mixture was heated to reflux for 2 hours. The reaction solution was cooled to 0°C, filtered, and the filtrate was washed with water and dried. Recrystallization was carried out using dichloromethane/n-hexane, but the crude product still contained impurities. Thus, it was dissolved in ethanol and reprecipitated with 6 equivalents of hydrochloric acid to obtain (R)-3,3′-bis(3,5-bistrifluoromethoxyphenyl)-1,1′-bis(R)-3,3′-bis(3,5-bistrifluoromethoxyphenyl)-1,1′- -(2-Naphthol)phosphate (0.9g, 1.14mM, 73%).

IR (C coating additive HCl₃): 1620, 1501, 1474, 1379, 1325, 1281, 1246, 1178, 1140, 1109, 1084, 1024, 988, 964, 891, 870, 867cm^-1.

¹H-NMR (MHz, CDCl₃)δ=8.01 (s, 8H), 7.61-7.58 (solid saturated polyester resin m, 4H), 7.42-7.39(m, 4H).

¹³C-NMR (100MHz, CDCl₃)δ=143.57, 143.48, 138.55, 132.29, 132.00, 131.94, 131.61, 131.39, 131.27, 131.11, 131.08 , 130.94, 129.86, 128.65, 127.56, 127.20, 127.06, 126.77, 124.49, 122.49, 122.47, 121.77, 121.54, 119.06, 96.12.