General procedure for the synthesis of nootkatone (compound 9) from compound (CAS: 72453-44-2): sodium acetate trihydrate (0.22 g, 1.6 mmol) was added to a single necked round bottomed flask equipped with a reflux condenser. Chloroenone compound 8 (0.14 g, 0.54 mmol) was dissolved in glacial acetic acid (4 mL) and the solution was injected into the flask. The mixture was heated to 100 °C and kept at this temperature for 2 hours. After completion of the reaction, the mixture was cooled to room temperature, poured into cold water and extracted with chloroform. The organic layer was washed sequentially with 2% aqueous KOH solution, 2N HCl, NaHCO3 solution and brine and then dried with MgSO4. Excess solvent was removed by rotary evaporator to give Nootkatone as a yellow oil in 93% yield. The total yield of pathway b (from β-pinene to Nootkatone) was 23% and that of pathway a was 25%, both showing higher yields. The enantiomeric purity of the final product was almost unchanged from that of the starting material, β-pinene, due to the fact that both the Oxy-Cope reaction and the methylation step preserve the enantiomeric purity. Qualitative analysis showed that the aroma of the synthesized Nootkatone was consistent with that of Nootkatone from other sources. Its 1H NMR data (250 MHz, CDCl3) were in agreement with literature reports: δ 5.77 (s, 1H), 4.75-4.72 (m, 2H), 2.62-2.43 (m, 1H), 2.41-2.22 (m, 4H), 2.09-1.87 (m, 3H), 1.46-1.38 (m, 1H), 1.12- 1.10 (m, 4H), 0.98 (d, 3H). In addition, the use of quaternary ammonium compounds, polyethylene glycol (PEG), or tris[2-(2-methoxyethoxy)ethyl]amine, etc., instead of 18-crown-6 as phase transfer catalysts or metal chelating agents, may be considered in the Oxy-Cope reaction to reduce the cost.
