반응 #464247

반응 방정식

AlMe3

n-BuLi

NH4Cl

paraformaldehyde

1-hexyne

→

alcohol

수율 77.0%

(E)-3-Methyl-hept-2-en-1-ol

수율 77.0%

용매

THF

THF

반응 조건

후처리

1. 1
   workup.DISSOLUTIONdissolved in 20 mL
2. 2
   기타at RT
3. 3
   workup.STIRRINGto stir at RT for 16 h
4. 4
   기타The volatile components were evaporated under reduced pressure (maximum 50° C., 0.3 mmHg, 12 h)
5. 5
   추출The remaining orange-yellow organic residue was extracted with dry hexanes (4×30 mL)
6. 6
   추출the yellow extract
7. 7
   기타was transferred to a 500 mL round-bottom flask via cannula
8. 8
   workup.STIRRINGThe resulting orange-yellow slurry was stirred from 0° C. to RT for 1.5 h
9. 9
   workup.DISSOLUTIONto dissolve the precipitate
10. 10
    workup.STIRRINGto stir at RT for 20 h before it
11. 11
    workup.ADDITIONIce was added
12. 12
    workup.ADDITIONto dilute
13. 13
    기타the reaction
14. 14
    기타The ice bath was removed
15. 15
    기타The organic layer was separated
16. 16
    추출the aqueous layer was extracted with ether (2×150 mL)
17. 17
    세척washed with a saturated solution NaHCO3 (200 mL)
18. 18
    건조dried with Na2SO4
19. 19
    여과filtered
20. 20
    농축concentrated under reduced pressure
21. 21
    기타to provide crude allylic alcohol 13b
22. 22
    기타The crude product was purified by flash chromatography (20% EtOAc in hexanes as eluant)

실험 절차

To a white slurry solution of zirconocene dichloride (7.3 g, 25 mmol) in 60 mL (CH2)2Cl2 was added AlMe3 (25 mL, 2.0M in hexanes, 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, 2.5M 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 ; CIHRMS (NH3 gas) calcd for C8H16O1 (M+) 128.1201, found: 128.1199.

출처