Carbonocyanidic acid, methyl ester → 2-Carbomethoxybicyclo[3.2.1]octan-3-one

Participants

Reaction Conditions

Reaction Steps

To bicyclo(3.2.1)octan-3-one, 227 (6.42 g, 51.7 mmol) in THF (75 mL), lithium diisopropyl amide (31 mL, 62 mmol) in THF (125 mL) was added dropwise at −78° C. The mixture was stirred at −78° C. for 1 h and methyl cyanoformate (4.9 mL, 62 mmol) was added. The cooling bath was removed and the reaction allowed to warm to room temperature. After stirring for 2 h, saturated aqueous NaCl (32 mL) was added and about half of THF removed on a rotary evaporator. The remaining solvent was extracted with ether (3×150 mL) and the dried (Na2SO4) ether layer concentrated to dryness. The residue was purified by flash chromatography (eluent: 10% EtOAc/hexanes) to afford 7.85 g (83%) of 3 as a colorless oil: Rf0.56 (10% EtOAc/bexanes); 1H-NMR (75:15:10 mixture of 2-en-3-ol, 2-α, and 2-β-carbomethoxy-3-keto tautomers) δ11.87 (s, 1H); 3.73 (s, 3H), 3.70 (s, 0.6H), 3.69 (s, 0.4H), 3.42 (m, 0.2H), 3.19 (m, 0.13H), 2.93 (m, 1H), 2.81 (m, 0.13H), 2.71 (m, 0.2H), 2.65 (ddd, 0.13H), J=18, 4, 2 Hz), 2.55 (ddd, 1.2H, J=18, 4, 2 Hz), 2.41 (m, 1H), 2.34 (m, 0.2H), 2.29 (m, 0.13H), 2.03 (dd, 1H, J=18, 2 Hz), 1.65-1.95 (m, 4.4H), 1.30-1.55 (m, 3.6H). 13C-NMR (only the signals corresponding to the 2-en-3-ol tautomer are reported) δ172.00, 171.19, 105.38, 51.33, 40.19, 35.92, 35.58, 32.91 (2C), 29.90.

Provenance & Evidence