(+)-(1S,2S)--1,2-dicarboxylic acid (CAS NO.: ), which is known as 1,2-Cyclopropanedicarboxylic acid, (1S,2S)-(+)-, could be produced through the following synthetic routes.

A. (-)-Dimenthyl succinate. A 300-mL. one-necked, round-bottomed flask is equipped with a magnetic stirrer, a Dean–Stark trap, and a reflux condenser. The flask is charged with 20 g (0.2 mol) of succinic anhydride, 62.5 g (0.4 mol) of l-menthol, 250 mg (1.3 mmol) of p-toluenesulfonic acid monohydrate, and 150 mL of toluene. The mixture is heated under reflux in an oil bath (about 140°C) for 24 hr. During this period the theoretical amount of water (3.6 mL) is collected. The mixture is allowed to cool to ambient temperature, diluted with 200 mL of hexane, and poured into a mixture of 250 mL of aqueous saturated sodium bicarbonate, 100 mL of methanol, and 200 mL of water. The organic phase is separated and the aqueous phase is extracted twice with 100 mL of hexane. The organic phases are combined, washed once with 200 mL of saturated brine, and dried over sodium sulfate. The solvent is removed with a rotary evaporator, and the resulting crude product is dissolved in 100 mL of methanol. After the solution stands in a refrigerator overnight, colorless crystals appear in the mixture and are collected by filtration with suction. This material (ca. 70 g in two crops) is purified by recrystallization from methanol to afford 66 g (84%) of pure (-)-dimenthyl succinate, mp 63–64°C.

B. (-)-Dimenthyl (1S,2S)-cyclopropane-1,2-dicarboxylate. A dry, 500-mL, three-necked, round-bottomed flask containing a magnetic stirring bar is equipped with a 100-mL pressure-equalizing dropping funnel, a rubber septum, and a three-way stopcock with a nitrogen inlet. The air in the system is replaced with dry nitrogen. The flask is charged with 180 mL of dry tetrahydrofuran and cooled with an ice bath; 74.1 mL of a 1.7 M hexane solution of butyllithium (126 mmol) is added. This solution is stirred while 21.3 mL (126 mmol) of 2,2,6,6-tetramethylpiperidine is added dropwise with a syringe through the septum over a 10-min period. The resulting solution of lithium 2,2,6,6-tetramethylpiperidide (LTMP) is cooled to -78°C with a dry ice–methanol bath and stirred. A solution of 23.7 g (60 mmol) of (-)-dimenthyl succinate in 50 mL of dry tetrahydrofuran is then added dropwise through the addition funnel over a 1-hr period. The wall of the funnel is rinsed with 10 mL of dry tetrahydrofuran and the rinse is added to the solution. The resulting yellow solution of succinate dianion is stirred for 1 hr. To the solution is added dropwise 3.9 mL (60 mmol) of bromochloromethane with a syringe through the septum over a 10-min period. After the reaction mixture is stirred for 2 hr, 2.2 mL (24 mmol) of isobutyraldehyde is added dropwise to quench any unreacted anions (Note 10). After being stirred for an additional 30 min, the reaction mixture is poured into 250 mL of ice-cooled 1 N hydrochloric acid and the product is extracted 3 times with 150 mL of ether. The combined organic phases are washed with 250 mL of brine, dried over sodium sulfate, filtered, and concentrated with a rotary evaporator. The residue is chromatographed on 700 g of silica gel packed in a 9.5-cm-diameter column using a mixture of ether and hexane (1 : 18) as eluant. The appropriate fractions are collected and concentrated to give 11.5 g (47%) of (-)-dimenthyl (1S,2S)-cyclopropane-1,2-dicarboxylate as colorless crystals. Analysis by GC indicates a diastereomeric ratio of 96 : 4. Recrystallization of this material from 25 mL of methanol affords 9–10 g (38–40%) of optically pure product, mp 95–96°C.

C. (+)-(1S,2S)-Cyclopropane-1,2-dicarboxylic acid (CAS NO.: ). (-)-Dimenthyl (1S,2S)-cyclopropane-1,2-dicarboxylate (4.06 g, 10 mmol, [α]_D25 + 17.8°) is dissolved in 20 mL of a 10% potassium hydroxide solution in 9 : 1 methanol/water in a 50-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar. The solution is heated at 60°C with an oil bath. Progress of the reaction is monitored by TLC on silica gel, using 1 : 1 hexane/ethyl acetate as eluant. After about 4 hr the resulting two-phase mixture is diluted with 20 mL of water and extracted with three 40-mL portions of ether. The aqueous layer is acidified by the addition of 20 mL of ice-cold 6 N hydrochloric acid, saturated with ca. 5 g of sodium chloride, and extracted with five 40-mL portions of ether. The combined organic layers are dried over sodium sulfate, diluted with 5 mL of hexane, and concentrated with a rotary evaporator. Filtration provides 1.17 g (90%) of (+)-(1S,2S)-cyclopropane-1,2-dicarboxylic acid, mp 172–173°C, [α]_D25 +228° (ethanol, c 1.01) [lit. mp 169.5–170°C, [α]_D25 +227.9° (ethanol, c 2.342)].