Reaction Steps
An oven-dried 500 mL 2-neck flask equipped with magnetic stirbar and addition funnel was charged with diisopropylamine (12.8 mL, 91.1 mmol) and THF (180 mL) under nitrogen. The solution was chilled to −25° C. in a dry ice/water/ethanol bath, and n-butyllithium (34 mL of a 2.65 M solution in hexanes, 89.0 mmol) was added dropwise via addition funnel. The solution was stirred for 30 min, after which a degassed solution of undecenoic acid (8.0 g, 43.4 mmol) in THF (44 mL) was added dropwise via addition funnel, causing the solution to become turbid. HMPA (8 mL, 43.4 mmol) was added via addition funnel. The cooling bath was then removed to allow the solution to warm to room temperature over 30 min, during which time the solution turned clear and yellow. The solution was cooled again to −25° C. A second 500 mL 2-neck flask under N2(g) purge was charged with CO2(s) (200 g, 4.5 mol) and chilled to −25° C. The enolate solution was cannula transferred onto the CO2(s) under N2(g) purge, causing the solution to become clear and colorless. The solution was stirred at −25° C. for 30 minutes then the cooling bath was removed and stirring continued at 22° C. overnight, during which time the reaction gelled. The reaction was quenched by the addition of 10% HCl (aq) (100 mL), causing two layers to form. This biphasic mixture was transferred to a reparatory funnel, and the organic layer was collected and the aqueous layer was extracted with ether (3×75 mL). The combined organic layers were then washed successively with 2M HCl (aq) (3×50 mL), water (75 mL), saturated NaCl (aq) (75 mL), and then dried over anhydrous MgSO4 (s). The solvent was removed on a rotary evaporator to yield 9.5 g of white solid. The crude product was recrystallized from heptane to yield white crystals. Yield: 9.07 g (92% yield). 1H NMR (300 MHz, DMSO-d6, 22° C.): δ (ppm) 12.62 (s, 2H, CH(COOH)2), 5.78 (ddt, JH—H3=17.0, 10.3, 6.8 Hz, 1H, CH2═CHCH2), 4.98 (ddt, JH—H3=17.2, 1.6 Hz, JH—H32.2 Hz, 1H, CH2═CHCH2), 4.93 (ddt, JH—H3=10.2, 1.2 Hz, JH—H2=2.3 Hz, 1H, CH2═CHCH2), 3.17 (t, JH—H3=7.5 Hz, 1H, CH(COOH)2), 2.00 (dt, JH—H3=7.0, 6.8 Hz, 2H, CH2═CHCH2), 1.73-1.63 (m, 2H, CH2CH(COOH)2), 1.40-1.16 (m, 10H, CH2═CHCH2(CH2)5CH2CH(COOH)2). 13C NMR (75 MHz, DMSO-d6, 22° C.): δ (ppm) 170.90, 138.82, 114.64, 51.60, 33.18, 28.69, 28.64, 28.41, 28.24, 26.79. ESI-MS: calcd. for C12H20O4Na [M+Na]+251.1, found 251.1.
