反应详情

To a solution of 5a (937 mg, 2.76 mmol) and activated 4 Å molecular sieves (280 mg) in CH2Cl2 (26 mL) at −20° C. was added diethyl-L(+)-tartrate (568 mg, 2.75 mmol), and Ti(OiPr)4 (629 mg, 2.2 mmol). After stirring for 1 h, tBuOOH (1.1 mL, 5.0-6.0 M in decane, predried over 4 Å molecular sieves for 1 h) was added with a syringe. The reaction mixture was kept in the freezer at −20° C. for 60 h. The solution was removed from the freezer, diluted with Et2O (5.2 mL) and quenched with a saturated Na2SO4 solution (2.6 mL). The resulting heterogeneous mixture was stirred and allowed to warm to room temperature for 2 h. Then it was filtered through a celite pad (washing with hot EtOAc several times). The combined filtrates were concentrated under vacuum. The residue was dissolved in Et2O (13 mL) at 0° C. and a 1N NaOH solution saturated with NaCl was added (8 mL). The two-phase mixture was vigorously stirred at 0° C. for 1 h and then transfered to a separatory funnel. The aqueous layer was separated and extracted 3 times with EtOAc. The combined organic extracts were dried over MgSO4 and concentrated under reduced pressure to give 651 mg (66% yield) of the crude product 6a as a clear oil with 92% ee and sufficiently pure for the subsequent reaction. Epoxide 6a was analyzed for enantiomeric purity using a Chiralcel OD-H column with 98.5:1.5 hexane:iPrOH as the eluent, using the racemate as the standard. 1H NMR (300 MHz, CDCl3) δ0.27 (s, 9H), 0.9 (t, J=7.5 Hz, 3H), 1.79 (m, 1H), 1.97 (m, 1H), 3.23 (t, J=5.8 Hz, 1H), 3.45 (s, 3H), 3.9 (m, 2H), 3.99 (s, 3H), 4.64-4.72 (m, 4H), 7.09 (s, 1H); 13C NMR (75 MHz, CDCl3) δ−1.93, 9.18, 25.63, 29.66, 53.42, 55.59, 60.64, 61.21, 63.46, 64.63, 96.44, 115.45, 121.32, 148.36, 161.89, 165.16; IR (film, NaCl, cm−1) 3463, 2945, 1562, 1451, 1345, 1041, 840; LRMS (70 eV, EI) m/z (rel int %) 355 (M+), 340, 324, 310, 294, 280, 262, 250, 89, 73, 57. HRMS m/z calcd for C17H29NO5Si (M+) 355.1815, found 355.1812, [α]23D=+28(c=0.25, CH2Cl2).

1. waitThe reaction mixture was kept in the freezer at −20° C. for 60 h
2. customThe solution was removed from the freezer
3. additiondiluted with Et2O (5.2 mL)
4. customquenched with a saturated Na2SO4 solution (2.6 mL)
5. stirringThe resulting heterogeneous mixture was stirred
6. filtrationThen it was filtered through a celite pad (washing with hot EtOAc several times)
7. concentrationThe combined filtrates were concentrated under vacuum
8. dissolutionThe residue was dissolved in Et2O (13 mL) at 0° C.
9. additiona 1N NaOH solution saturated with NaCl was added (8 mL)
10. stirringThe two-phase mixture was vigorously stirred at 0° C. for 1 h
11. customtransfered to a separatory funnel
12. customThe aqueous layer was separated
13. extractionextracted 3 times with EtOAc
14. dry with materialThe combined organic extracts were dried over MgSO4
15. concentrationconcentrated under reduced pressure