反応 #60368

反応方程式

7-Cyanochroman-4-one

(1S, 2S)-(+)—N-p-Tosyl-1,2-diphenylethylenediamine

ruthenium

→

ruthenium

title compound

(S)-4-hydroxy-chroman-7-carbonitrile

溶媒

CH3CN

Et3N

formic acid

H2O

i-PrOH

Et3N

formic acid

反応条件

後処理

1. 1
   濃縮The reaction was concentrated under reduced pressure to ˜5 ml
2. 2
   温度The mixture was cooled to −20° C.
3. 3
   workup.ADDITION10 mL of H2O was added
4. 4
   workup.STIRRINGwith shaking
5. 5
   ろ過The solid was filtered
6. 6
   洗浄washed with H2O
7. 7
   その他to provide the desired chiral complex
8. 8
   その他The complex was dried in vacuo
9. 9
   workup.ADDITIONA 5/2 mixture of formic acid and Et3N
10. 10
    その他was prepared
11. 11
    温度were heated to 100° C. under reduced pressure (˜100 mm Hg)
12. 12
    その他to remove volatile chemicals
13. 13
    その他The residue was used without further purification
14. 14
    workup.STIRRINGThe reaction was stirred at RT for 14 h
15. 15
    抽出the mixture was extracted with EtOAc (300 ml, 3×)
16. 16
    洗浄washed sequentially with a saturated NaHCO3 solution and brine
17. 17
    乾燥The organic solution was dried over MgSO4
18. 18
    ろ過filtered
19. 19
    濃縮concentrated in vacuo
20. 20
    その他to provide a crude brown solid which
21. 21
    その他was purified by flash column chromatography (silica, 50% EtOAc in hexane)

実験手順

A ruthenium chiral complex was prepared as follows: (1S, 2S)-(+)—N-p-Tosyl-1,2-diphenylethylenediamine (1.10 g, 3.0 mmol, Aldrich) and [RuCl2(η6-para-cymene)]2 (0.92 g, 1.5 mmol, STREM) were dissolved in 35 ml of i-PrOH and stirred at 80° C. for 1 h. The reaction was concentrated under reduced pressure to ˜5 ml. The mixture was cooled to −20° C., and 10 mL of H2O was added with shaking. The solution was scratched with a spatula until it all solidifies. The solid was filtered and washed with H2O to provide the desired chiral complex. The complex was dried in vacuo. A 5/2 mixture of formic acid and Et3N was prepared as follows: A mixture of formic acid (190 ml, 232 g, 5.03 mmol) and Et3N (280 mL, 203 g, 2.01 mmol) were heated to 100° C. under reduced pressure (˜100 mm Hg) to remove volatile chemicals. The residue was used without further purification. 7-Cyanochroman-4-one (10.2 g, 58.9 mmol) and a 5/2 mixture of formic acid and Et3N (50 mL) were dissolved in CH3CN (120 ml). The ruthenium chiral complex (S, S—, 0.380 g, 0.589 mmol) was added. The reaction was stirred at RT for 14 h. After the addition of H2O (100 mL), the mixture was extracted with EtOAc (300 ml, 3×). The organic phases were combined and washed sequentially with a saturated NaHCO3 solution and brine. The organic solution was dried over MgSO4, filtered and concentrated in vacuo to provide a crude brown solid which was purified by flash column chromatography (silica, 50% EtOAc in hexane) to provide the title compound.

出典