反应详情

Alternatively, the trifluoromethyl (or other prochiral) ketones of formula G or J (scheme 2) were asymmetrically reduced as follows (see for example: Corey, E. J. & Link, J. O. A General, Catalytic, and Enantioselective Synthesis of Alpha-amino Acids. J. Am. Chem. Soc. 114, 1906-1908 (1992)): Catechol borane (95 mL, 1 M in THF) and (S)-2-methyl-CBS oxazaborolidine (2.6 g, 9.6 mmol) were mixed in a jacketed glass reactor. The mixture was stirred at RT for 20 min, then the jacket was cooled to −78° C. At a reaction temperature of −65° C., 1-[4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethanone (16 g, 48 mmol) in THF (150 mL) was added dropwise over 2 h. The reaction was then warmed to −36° C. and held at this temperature for 22 h. Then the reaction was quenched with 3 N NaOH (100 mL) while maintaining a reaction temperature of <−25° C. The reaction was then warmed to 0° C. and H2O2 (30%, 100 mL) was added over 30 min, then warmed to RT for 4 h. The reaction mixture was quenched with 1 N NaOH, extracted with ether, washed with brine, dried over Na2SO4, and concentrated in vacuo. Purification on normal phase silica gel chromatography (EtOAc/heptane) provided the product as a viscous oil.

1. temperaturethe jacket was cooled to −78° C
2. temperatureThe reaction was then warmed to −36° C.
3. waitheld at this temperature for 22 h
4. customThen the reaction was quenched with 3 N NaOH (100 mL)
5. temperaturewhile maintaining a reaction temperature of <−25° C
6. temperatureThe reaction was then warmed to 0° C.
7. additionH2O2 (30%, 100 mL) was added over 30 min
8. temperaturewarmed to RT for 4 h
9. customThe reaction mixture was quenched with 1 N NaOH
10. extractionextracted with ether
11. washwashed with brine
12. dry with materialdried over Na2SO4
13. concentrationconcentrated in vacuo
14. customPurification on normal phase silica gel chromatography (EtOAc/heptane)