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0 °C

Zirconocene dichloride (1.66 g, 5.6 mmol) was treated with dichloroethane (22 mL) and trimethylaluminum solution (23 mmol, 2.0 M in heptane) was added. The clear yellow solution was stirred for 0.75 h and cooled to 0° C. 5-chloro-1-pentyne was added neat over 1 h at 0° C. and stirred 10 h at room temperature. The clear brown solution was concentrated in vacuo and triturated with anhydrous hexanes (3×5 mL), the solvent being removed after each iteration via vacuum. Hexanes (10 mL) was then added and the solution cannulated away from the solids. The solids were rinsed with hexanes (5 mL) and the combined hexane solutions diluted with THF (80 mL). A prepared solution of 1-(chloromethyl)-2,5-dimethoxy-3,4,6-trimethylbenzene (4.009 g, 17.5 mmol) in THF (10 mL) was added to the vinyl alane via cannula and the combined solution cooled to 10° C. The catalyst was prepared by treating bis-(triphenylphosphine)nickel dichloride (579 mg, 0.87 mmol) in THF (5 mL) with n-BuLi (1.6 M in hexanes, 1.75 mmol). The blood-red clear catalyst solution was then added via cannula to the 10° C. vinyl alane solution and let warm to room temperature over 7 h. The reaction was cooled to 0° C. and quenched by slow addition of 2.5 M HCl (100 mL) over 0.5 h followed by hexanes (100 mL) and separation. The aqueous layer was extracted 2×100 mL hexanes, 1×50 mL 50% EtOAc/hexanes and the combined organics washed once with brine (100 mL) and dried over anhydrous Na2SO4 and concentrated to a brown oil. Multiple flash chromatography yielded 5.2 g of (E)-1-(7-chloro-3-methylhept-2-enyl)-2,5-dimethoxy-3,4,6-trimethylbenzene as a clear oil (94.6%). 1H NMR (400 MHz, CDCl3) d 5.05 (t, J=6.4 Hz, 1H), 3.63 (S, 6H), 3.49 (t, J=6.4 Hz, 2H), 3.35 (d, J=8.4 Hz, 1H), 2.16 (s, 9H), 1.98 (t, J=7.6 Hz, 2H), 1.76 (s, 3H), 1.70 (m, 2H), 1.52 (m, 2H). 13C NMR (100 MHz, CDCl3) d 153.0, 152.7, 134.4, 131.4, 128.3, 127.9, 127.6, 123.8, 60.9, 60.1, 45.0, 38.8, 32.2, 26.1, 25.1, 16.1, 12.8, 12.7, 12.2.

1. additionwas added
2. stirringstirred 10 h at room temperature
3. concentrationThe clear brown solution was concentrated in vacuo
4. customtriturated with anhydrous hexanes (3×5 mL)
5. customthe solvent being removed after each iteration via vacuum
6. additionHexanes (10 mL) was then added
7. washThe solids were rinsed with hexanes (5 mL)
8. additionthe combined hexane solutions diluted with THF (80 mL)
9. temperaturethe combined solution cooled to 10° C
10. customThe catalyst was prepared
11. additionThe blood-red clear catalyst solution was then added via cannula to the 10° C. vinyl alane solution
12. temperaturelet warm to room temperature over 7 h
13. temperatureThe reaction was cooled to 0° C.
14. customquenched by slow addition of 2.5 M HCl (100 mL) over 0.5 h
15. customfollowed by hexanes (100 mL) and separation
16. extractionThe aqueous layer was extracted 2×100 mL hexanes, 1×50 mL 50% EtOAc/hexanes
17. washthe combined organics washed once with brine (100 mL)
18. dry with materialdried over anhydrous Na2SO4
19. concentrationconcentrated to a brown oil