Diethyl Ether → 3-(1-Octen-1-yl)-4-isopropylcyclohexanone

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A 10 mL round-bottom flask equipped with a stir bar was charged with zirconocene chloride hydride (0.301 g, 1.04 mmol) and sealed with a septum. The flask was evacuated with a vacuum pump and purged with argon, the process being repeated 3 times. THF (4 mL) was injected and the mixture stirred to generate a white slurry which was treated via syringe with 1-octyne (0.115 g, 1.04 mmol). The mixture was stirred for 15 minutes to yield a yellow-to-green solution which was cooled to -78° C. and treated via syringe with ethereal MeLi (0.65 mL, 1.03 mmol) to generate a dark red solution. At the same time, a 5 mL flask with septum was purged as above with Ar and then 1 mL of THF was added via syringe. To this flask at -78° C. was added ZnMe2 in heptane (0.44 mL, 0.53 mmol), followed by MeLi in Et2O (0.33 mL, 0.53 mmol). After 5 minutes the solution was warmed to 0° C. for 10 minutes to afford a clear solution, which was then cooled to -78° C. Concurrently, CuI (20.7 mg, 0.109 mmol) was placed in a 10 mL round-bottom flask equipped with a stir bar, and sealed under septum. The flask was evacuated and purged with argon as above and THF (1 mL) added via syringe. To this slurry at -78° C. was then added MeLi in Et2O (0.136 mL, 0.217 mmol). The slurry was warmed slightly to generate a clear solution of Me2CuLi, then cooled to -78° C. At -78° C. and by cannula the solution of Me3ZnLi was added to the Me2CuLi solution. The solution of the zirconocene was added via cannula to the resulting Me2CuLi/Me3ZnLi solution, thereby providing a reaction mixture comprising 20 mol-% of copper per mole of substrate enone. The mixture was stirred for 15 minutes at -78° C. to yield a dark red solution which was treated with 4-isopropyl-2-cyclohexenone (77 μL, 0.5 mmol) as a neat liquid over 70 minutes. After 1 hour of additional stirring the mixture was quenched with 5 mL of 10% NH4OH in saturated NH4Cl. The product was extracted with 3×20 mL of ether and dried over Na2SO4. The solution was then filtered through fritted filter paper and the solvent removed in vacuo. The resulting residue was submitted to flash chromatography on silica gel (Petroleum Ether/Ethyl Acetate 40/1) to give a 92% yield (115.3 mg) of the product as a colorless oil giving satisfactory IR, NMR, MS and HRMS data.

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