A kind of benzimidazolo chiral heterocyclic compound and its preparation method and application
A technology of benzimidazoles and heterocycles, applied in the field of chiral compound synthesis, to achieve high regioselectivity, high catalytic activity, and broaden the scope of application
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Embodiment 1
[0116] Example 1.O,O'-[(R)-(1,1'-binaphthyl-2,2'-diphenolyl)]-N-[(R)-2-methyl-1,2, Preparation of 3,4-tetrahydroquinolinyl] phosphoramidite (L5):
[0117]Under nitrogen protection, in a dry 250mL three-neck flask, add 50mL of toluene and phosphorus trichloride (0.67mL, 7.7mmol), and cool to 0°C; in another dry 50mL eggplant-shaped bottle, add (R) -2-Methyl-1,2,3,4-tetrahydroquinoline (1.13g, 7.7mmol), toluene (8mL), and triethylamine (1.8mL, 12.9mmol), then gradually added dropwise to the above 250mL in the three-necked flask. After the dropwise addition, the temperature was raised to 80°C for 6 hours, and then gradually cooled to -78°C. A solution of (R)-binaphthalene (7.7 mmol) and triethylamine (3.5 mL, 25.2 mmol) in toluene (30 mL) and tetrahydrofuran (6 mL) was slowly added to the system. The system was stirred overnight at room temperature, filtered through celite, and the solvent was removed under reduced pressure. The crude product was separated and purified by colu...
Embodiment 2
[0121] Example 2. (S)-[6,6'-((R,R)-2,4-pentanedioloxy)]-2,2'-N,N-bis[(1R)-1-benzene Preparation of ethyl ethyl] phosphoramidite (L12):
[0122] Under nitrogen protection, phosphorus trichloride (32.30 μ L, 0.37 mmol), triethylamine (257.90 μ L, 1.85 mmol), bis[(1R)-1-phenylethyl]amine ( 83.70μL, 0.37mmol), anhydrous toluene (20mL), and then stirred at 50°C for 4h. Cool to room temperature, add (S)-[6,6'-((2R,4R)-2,4-pentanedioloxy)]-2,2'-dihydroxybiphenyl (105.86mg, 0.37mmol) Tetrahydrofuran solution (20 mL) was stirred at room temperature for 16 h. The crude product was purified by column chromatography to obtain the target compound.
[0123] (S)-[6,6-(2R,4R-Pentadioxy)]-(1,1')-biphenyl-(3,5-dioxa-4-phosphacyclohepta[e,g][1,4])-bis ((R)-1-phenylethyl)amine (L12)
[0124]
[0125] White solid, yield: 84%; melting point: 109.6–110.3°C; [α] D 27 =+59 (c=0.1, CHCl 3 ). 1 H NMR (400MHz, CDCl 3 )δ7.31–7.25(m,2H),7.16–7.10(m,2H),6.98(dd,J=13.6,8.2Hz,2H),6.89(t,J=7.5Hz,2...
Embodiment 3
[0126] Example 3. (R)-[6,6'-((S,S)-2,3-butanedioloxy)]-2,2'-N-[(R)-2-methyl-1 , Preparation of 2,3,4-tetrahydroquinolinyl] phosphoramidite (L13):
[0127] In a dry 250mL three-necked flask, add (R)-[6,6'-((S,S)-2,3-butanedioloxy)]-2,2'-dihydroxybiphenyl ( 2.00g, 7.3mmol) and toluene (50mL), phosphorus trichloride (9.60mL, 110.00mmol) and N-methylpyrrolidone (21.00μL, 0.22mmol) were added under nitrogen protection respectively, reacted at 50°C for 30min, and then The reaction solution was cooled to room temperature, and then the phosphorus trichloride was distilled off under reduced pressure, and then the phosphorous oxychloride solid obtained after concentration was dissolved with 50 mL of tetrahydrofuran; in another dry 250 mL round bottom flask, (R)-2- Methyl-1,2,3,4-tetrahydroquinoline hydrochloride (1.20g, 6.60mmol) and 30mL of tetrahydrofuran were cooled to -78°C, and then n-butyllithium (2.5 mol / L, 5.30mL), continue to stir and react for 1h after the dropwise addition;...
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