反应详情

To a white slurry solution of zirconocene dichloride (7.3 g, 25 mmol) in 60 mL (CH2)2Cl2 was added AlMe3 (25 mL, 2.0 M in hexane, 50 mmol) at 0° C., stirred for 30 min, and then warmed to RT for 1.0 h. To this lemon-yellow solution was added 1-hexyne 19b (2.05 gm, 25 mmol, dissolved in 20 mL (CH2)2Cl2 at RT. the reaction was allowed to stir at RT for 16 h. The volatile components were evaporated under reduced pressure (maximum 50° C., 0.3 mmHg, 12 h). The remaining orange-yellow organic residue was extracted with dry hexanes (4×30 mL), and the yellow extract was transferred to a 500 mL round-bottom flask via cannula. To this was added n-BuLi (10 mL, 2.5 M in hexanes, 25 mmol) at 0° C. The resulting orange-yellow slurry was stirred from 0° C. to RT for 1.5 h, and then THF (50 mL) was added to dissolve the precipitate. The resulting solution (which was homogeneous and brown-yellow in color) was cannulated to a suspension of paraformaldehyde (3.75 g, 125 mmol) in THF (50 mL) under a N2 atmosphere. This orange-yellow suspension was allowed to stir at RT for 20 h before it was cooled to 0° C. (ice water bath). Ice was added to dilute the reaction, and then saturated NH4Cl (100 mL) was added. The ice bath was removed and the reaction was further acidified with 3 M HCl until the reaction turned to a clear yellow (homogeneous) solution. At this time, the reaction pH was measured as 2-3. The organic layer was separated, and the aqueous layer was extracted with ether (2×150 mL). The organic extracts were combined and washed with a saturated solution NaHCO3 (200 mL), then dried with Na2SO4, filtered and concentrated under reduced pressure to provide crude allylic alcohol 13b. The crude product was purified by flash chromatography (20% EtOAc in hexanes as eluant) to afford alcohol 13b. (2.46 g, 77% yield) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 5.37 (t, J=7.1 Hz, 1H), 4.11 (d, J=7.1 Hz, 2H), 1.98 (t, J=7.5 Hz, 2H), 1.64 (s, 3H), 1.37 (m, 2H), 1.28 (m, 2H), 0,87 (t, J=7.3 Hz, 3H); 13C NMR (67.5 MHz, CDCl3) δ 139.9, 123.1, 59.2, 39.2, 29.8,22.3, 16.1, 13.9; IR (neat) δ max: 3330, 2958, 2930, 1670, 1467, 1000 cm−1; ClHRMS (NH3 gas) calcd for C8H16O1 (M+) 128.1201, found: 128.1199.

1. dissolutiondissolved in 20 mL
2. customat RT
3. stirringto stir at RT for 16 h
4. customThe volatile components were evaporated under reduced pressure (maximum 50° C., 0.3 mmHg, 12 h)
5. extractionThe remaining orange-yellow organic residue was extracted with dry hexanes (4×30 mL)
6. extractionthe yellow extract
7. customwas transferred to a 500 mL round-bottom flask via cannula
8. stirringThe resulting orange-yellow slurry was stirred from 0° C. to RT for 1.5 h
9. dissolutionto dissolve the precipitate
10. stirringto stir at RT for 20 h before it
11. additionIce was added
12. additionto dilute
13. customthe reaction
14. customThe ice bath was removed
15. customThe organic layer was separated
16. extractionthe aqueous layer was extracted with ether (2×150 mL)
17. washwashed with a saturated solution NaHCO3 (200 mL)
18. dry with materialdried with Na2SO4
19. filtrationfiltered
20. concentrationconcentrated under reduced pressure
21. customto provide crude allylic alcohol 13b
22. customThe crude product was purified by flash chromatography (20% EtOAc in hexanes as eluant)