A. 2,2-Dimethylcyclohexane-1,3-dione. In a 1-L, three-necked, round-bottomed flask equipped with a magnetic stirrer, a 200-mL pressure-equalizing dropping funnel, and a reflux condenser (the top of which is connected to a calcium chloride drying tube) are placed 50.4 g (0.4 mol) of 2-methylcyclohexane-1,3-dione² and 500 mL of dry methanol. To this stirred solution is added dropwise 168 mL of commercial Triton B (40% in methanol) (Note 1) and (Note 2). After the additional is complete, the resulting solution is stirred at room temperature for 10 min and 60.0 g (0.423 mol) of methyl iodide is added portionwise. This solution is then stirred and heated under reflux for 16–20 hr (Note 3). After the reaction mixture is cooled to room temperature, about 400 mL of methanol is removed by rotary evaporation. The residue is poured into a mixture of 100 mL (1.2 mol) of concentrated hydrochloric acid and about 100 g of ice to decompose the O-alkylated product (Note 4), and the mixture is stirred for 30 min. The precipitated solid (recovered starting material) is collected by filtration and the filtrate is extracted 4 times with 100 mL of ethyl acetate. The combined ethyl acetate extracts are washed with 5% sodium thiosulfate solution (4 × 100 mL), saturated sodium hydrogen carbonate solution (2 × 100 mL) and saturated sodium chloride solution (100 mL), dried over anhydrous magnesium sulfate, and filtered. Ethyl acetate is removed by rotary evaporation and the residue is distilled to give 30–32 g (54–57%) of 2,2-dimethylcyclohexane-1,3-dione bp 92–97°C (4 mm) as a glassy solid (Note 5) and (Note 6).

B. (S)-(+)-3-Hydroxy-2,2-dimethylcyclohexanone. In a 5-L, three-necked, round-bottomed flask equipped with a mechanical stirrer, a thermometer, and an air-reflux condenser are placed 3 L of tap water and 450 g of sucrose (Note 7). The mixture is stirred at 30°C, and 200 g of dry baker's yeast (Note 8) is added with stirring, whereupon brisk fermentation takes place (Note 2). This fermenting mixture is stirred at 30°C for 10 min and a solution of 15 g (0.107 mol) of 2,2-dimethylcyclohexane-1,3-dione in 95% ethanol (30 mL) and 0.2% Triton X-100 (120 mL) is added portionwise (Note 9). The mixture is stirred at 30°C for 40–48 hr (Note 10). Diethyl ether (about 200 mL) and Celite (about 50 g) are then added to the mixture and it is left to stand overnight. After the flocculated yeast cells are precipitated, the mixture is filtered through a pad of Celite (Note 11). The filter cake is washed with ethyl acetate (2 × 100 mL) and the combined filtrate and washings are saturated with sodium chloride and extracted 4 times with 100 mL of ethyl acetate. The combined ethyl acetate extracts are washed with saturated sodium hydrogen carbonate solution (200 mL) and saturated sodium chloride solution (200 mL), dried over anhydrous magnesium sulfate, and filtered. Ethyl acetate is removed by rotary evaporation and the residue (about 20 g) is chromatographed over 200 g of silica gel (Fuji Davison 820 MH gel) (Note 12). Elution with hexane–ethyl acetate (10 : 1–5 : 1) gives 5–6 g of recovered starting material. Further elution with hexane-ethyl acetate (5 : 1–1 : 2) gives 7.7–7.9 g (47–52%) of (S)-3-hydroxy-2,2-dimethylcyclohexanone. An analytical sample can be obtained by distillation, bp 85–87°C at 3.7 mm, [α]²¹D + 23.0° (CHCl₃, c 2.0) (Note 13),(Note 14),(Note 15).