A. 3-Chloro-5,5-dimethylcyclohex-2-en-1-one (1)^3,4 (Note 1). An oven-dried, 250-mL, one-necked, round-bottomed flask is equipped with a magnetic stirring bar and graduated addition funnel topped with a nitrogen inlet. The flask is charged with dimedone (28.1 g, 200 mmol) and toluene (100 mL) (Note 2). The suspension is stirred while oxalyl chloride (35 mL, 400 mmol) is slowly added via the addition funnel over a 10-min period (Note 3). After the addition is complete and gas evolution has subsided, the addition funnel is quickly exchanged for a reflux condenser topped with a nitrogen inlet. The mixture is then heated at 60–70°C for 30 min, or until no more suspended dimedone remains and gas evolution has ceased. (Additional oxalyl chloride may be added until dimedone has completely reacted.) The reaction is allowed to cool and concentrated by rotary evaporation at reduced pressure. The crude red oil is distilled through a short path apparatus to give 3-chloro-5,5-dimethylcyclohex-2-en-1-one (1) (29.3 g, 93% yield) as a colorless oil, bp 68–71°C (6.0 mm) (Note 4).

B. 1,4-Dilithiobutane (2).^5,6,7 (All transfers are conducted under dry nitrogen; reagents are introduced into reaction vessels through rubber septa using a cannula or syringe.) An oven-dried, 1-L, three-necked, round-bottomed flask is equipped with a large magnetic stirring bar and glass beads (ca. 3-mm diameter), graduated addition funnel, stopper, and large diameter nitrogen inlet (at least 2 mm in diameter). The flask is purged with nitrogen, charged with anhydrous diethyl ether (250 mL) (Note 2), and cooled to 0°C. The stopper is removed from the flask and replaced with a conical funnel while a rapid flow of dry nitrogen is passed through the flask. Lithium wire, 1% Na (9.48 g, 1.36 mol, 4.5 eq.) (Note 5), prewashed with hexanes, is held with forceps over the funnel and cut with clean scissors into pieces no larger than 2 mm in length (Note 6) so that the freshly cut lithium pieces drop directly into the anhydrous ether. 1,4-Dichlorobutane (33.5 mL, 300 mmol) (Note 2) is then dissolved in anhydrous diethyl ether (85 mL) and introduced into the addition funnel; approximately 10% of this solution is introduced into the lithium/ether suspension, and the reaction is initiated by vigorous stirring. A white precipitate (LiCl) signaling initiation of the reaction should be apparent within 5 to 15 min, at which time the remainder of the solution is added dropwise over a 1 to 2-hr period (Note 7). The white suspension is rapidly stirred for 20 hr at 0°C.

The mixture is most conveniently filtered by gravity filtration through an oven-dried coarse (15 μM) sintered glass frit (Note 8), (Note 9). The concentration of 1,4-dilithiobutane (2) in ether is determined by titration with sec-butyl alcohol using 1,10-phenanthroline as indicator. The molarity of the solution obtained under these optimized conditions is approximately 1.7 M in "RLi", i.e., 0.9 M in 1,4-dilithiobutane (2) (Note 10). This solution is stable for several months when stored at −10°C under nitrogen.

C. 9,9-Dimethylspiro[4.5]decan-7-one (3).^6,7 (All transfers are conducted under dry nitrogen; reagents are introduced into reaction vessels through rubber septa using a cannula or syringe.) An oven-dried, 2-L, three-necked, round-bottomed flask is equipped with a graduated addition funnel, overhead mechanical stirrer, and a nitrogen inlet. The flask is purged with nitrogen and charged with copper(I) thiophenoxide (36.7 g, 212 mmol) and anhydrous tetrahydrofuran (400 mL) (Note 2), and the heterogeneous suspension is mechanically stirred while cooling in a −78°C cold bath (dry ice-acetone). 1,4-Dilithiobutane (2), 0.87 (± 0.02) M in diethyl ether (122 mL, 106 mmol) is added via the addition funnel over 5 min, and then the reaction mixture is allowed to slowly warm to −15°C (Note 11) over a 20 to 45-min period, during which time the initial yellow color changes to brown-red with concomitant dissolution of copper thiophenoxide. The addition funnel is washed with a few milliliters of anhydrous tetrahydrofuran, and a solution of 3-chloro-5,5-dimethylcyclohex-2-en-1-one (1) (15.85 g, 100 mmol) in anhydrous tetrahydrofuran (250 mL) is added dropwise over a 1 to 2-hr period, while the temperature of the cold bath is maintained at −15°C to −20°C. The reaction turns olive-green and then black as the chloroenone is added. After the addition is complete, the cold bath is removed and the reaction flask is allowed to warm to room temperature.

After 30 to 45 min, the reaction mixture is opened to the air and poured into approximately 500 mL of saturated aqueous ammonium chloride solution, diluted with approximately 500 mL of diethyl ether washings, and allowed to stir for 10 to 15 min. The resulting mixture is filtered through a Büchner funnel, washing with small portions of diethyl ether (Note 12). The layers are separated in a separatory funnel, the aqueous layer is extracted with diethyl ether, and the combined organic layers are washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride, dried over approximately 100 g of sodium sulfate, filtered through a Büchner funnel, and concentrated by rotary evaporation. The concentrated product may still contain solid diphenyl disulfide that can now be efficiently removed by chromatography of the neat crude product mixture through a 5-cm diameter × 10-cm height silica gel column and elution with hexane-diethyl ether (7:1) (Note 13). Evaporation of solvent by rotary evaporation at reduced pressure gives 13.28 g (74% yield) of 9,9-dimethylspiro[4.5]decan-7-one (3) as a pale yellow to colorless oil (Note 14).