反应详情

温度

14 °C

To a solution of olefin 2 (1.92 kg, 11.0 mol) in toluene (4.83 L) was added vanadyl acetylacetonate (VO(acac)2, 58.3 g, 0.22 mol) at 0° C. After a solution of TBHP (5.7 M in decane, 38.6 mL) was added to the solution at 0° C., the resulting suspension was allowed to warm to 14° C. Additional solution of TBHP (5.7 M in decane, 4.36 L) was slowly added to the reaction mixture over 50 min while maintaining the batch temperature between 14-28° C. The resulting suspension was stirred for another 2 h, and then heated at 40° C. for 8 h. Excess TBHP was quenched with aqueous Na2S2O3 solution (2.95 kg Na2S2O3 and 4.71 kg H2O), which was slowly added at 0° C. The resulting mixture was stirred at 20° C. for 1.5 h. The disappearance of peroxides was confirmed by test paper. The aqueous layer was separated and extracted with EtOAc (9.42 L×2). The combined organic solutions were washed with brine (6.33 L). The brine layer was back-extracted with EtOAc (3.42 L×4). GC assay of the combined organic solutions indicated product 3. The combined organic solutions were concentrated, and the resulting residue was purified by silica gel chromatography in a filter pot (first eluted with hexanes/EtOAc (4/1) then pure EtOAc). Analytically pure sample was prepared by flash silica gel column chromatography (hexanes/MTBE) followed by recrystallization (EtOAc) as pale yellow crystals: mp 31-33° C.; 1H NMR (400 MHz, CDCl3) δ 5.01 (dd, J=48.3, 3.9 Hz, 1H), 4.13 (br s, 1H), 3.86 (s, 3H), 3.71 (m, 1H), 3.59 (m, 1H), 2.77 (dd, J=32.8, 3.9 Hz, 1H), 2.30 (br s, 1H), 2.11 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 168.4 (d, J=24.1 Hz), 88.1 (d, J=186.1 Hz), 73.2 (d, J=1.6 Hz), 58.4, 57.1 (d, J=5.6 Hz), 52.8, 51.6 (d, J=19.3 Hz), 37.7 (d, J=1.6 Hz); 19F NMR (376 MHz, CDCl3) δ −200.8 (dd, J=48.3, 32.8 Hz); LRMS m/z 191 (M+1), 189 (M−1), 172 ([M−H2O]+), 59 ([COOCH3]+, base peak); [α]D25=−56 (c 1.0, CHCl3).

1. temperaturewhile maintaining the batch temperature between 14-28° C
2. temperatureheated at 40° C. for 8 h
3. customExcess TBHP was quenched with aqueous Na2S2O3 solution (2.95 kg Na2S2O3 and 4.71 kg H2O), which
4. additionwas slowly added at 0° C
5. stirringThe resulting mixture was stirred at 20° C. for 1.5 h
6. customThe aqueous layer was separated
7. extractionextracted with EtOAc (9.42 L×2)
8. washThe combined organic solutions were washed with brine (6.33 L)
9. extractionThe brine layer was back-extracted with EtOAc (3.42 L×4)
10. concentrationThe combined organic solutions were concentrated
11. customthe resulting residue was purified by silica gel chromatography in a filter pot (
12. washfirst eluted with hexanes/EtOAc (4/1)
13. customAnalytically pure sample was prepared by flash silica gel column chromatography (hexanes/MTBE)
14. customfollowed by recrystallization (EtOAc) as pale yellow crystals