A. Methyl 1,3-dimethyl-5-oxobicyclo[2.2.2]octane-2-carboxylate.² An oven-dried, 250-mL, round-bottomed flask equipped with a stirring bar and a rubber septum is charged with 100 mL of dry tetrahydrofuran and 5.56 g (55 mmol) of anhydrous diisopropylamine. The flask is flushed with argon via a needle inlet–outlet and cooled to −78°C with a dry ice–isopropyl alcohol bath (Note 1),(Note 2),(Note 3). To the stirred solution is added dropwise with a syringe 30 mL (54 mmol) of a 1.8 M solution of butyllithium in hexane (Note 4) to form lithium diisopropylamide, followed after 30 min by a solution of 5.50 g (50 mmol) of 3-methyl-2-cyclohexen-1-one (Note 5) in 60 mL of dry tetrahydrofuran via a flex-needle over a 15-min period. Stirring and cooling is continued for an additional 30 min. To the resulting yellow solution of the lithium dienolate, 10.0 g (0.1 mol) of methyl (E)-crotonate (Note 6) is added with a syringe within 2 min. The cooling bath is removed and the reaction mixture is allowed to warm to room temperature (Note 7). Stirring is continued at room temperature for 2 hr. The reaction mixture is quenched by adding 1 N hydrochloric acid until the mixture turns acidic. Extraction with three 80-mL portions of dichloromethane followed by evaporation of the solvent yields a light-yellow oil that is taken up in 100 mL of diethyl ether. This solution is filtered through 100 g of silica gel to remove polymers and water. Elution with diethyl ether and evaporation of the solvent gives a yellow oil that is distilled in a Kugelrohr distillation apparatus (Note 8) under reduced pressure. After a small forerun (ca. 0.5 g of unreacted 3-methyl-2-cyclohexen-1-one) at 50°C, 0.05 mm, the main fraction is collected at 110–120°C (oven temperature), 0.05 mm to give 8.25–9.43 g (78–90%) of a colorless oil, which solidifies on standing in the freezer. One recrystallization from cold pentane (approximately 10 mL of pentane per 8 g of ester mixture) gives 6.0 g of product as white crystals, mp 37°C (Note 9), of approximately 97% isomeric purity (Note 10).

B. 1,3-Dimethyl-5-oxobicyclo[2.2.2]octane-2-carboxylic acid. A mixture of 11.2 g (53.4 mmol) of the foregoing crude ester in 40 mL of methanol and 8.0 g (143 mmol) of potassium hydroxide in 16 mL of water is refluxed under argon until the ester is no longer present when monitored by TLC (Note 7). This takes about 1 day. Methanol is removed with a rotary evaporator, and the remaining dark solution is extracted with ether (2 × 50 mL), acidified to pH 1 with dilute sulfuric acid, and extracted with dichloromethane (4 × 50 mL). The organic layer is filtered through 100 g of silica gel and eluted with ether to remove most of the dark impurities. Concentration under reduced pressure gives 10.0 g of acid mixture. Distillation in a Kugelrohr apparatus at 180°C, 0.03 mm and one recrystallization from ether-pentane gives 7.0 g (67%) of pure bicyclic acid (isomeric purity >98%) as white crystals, mp 130–131°C (Note 11).