3-Methyl-2(5H)-furanone → Acetoacetic Acid

Participants

Reaction Conditions

Reaction Steps

2-C-Methyl-D-erythritol with a ca 80% e.e. was synthesized according to a Duvold, et al. (1997) Tetrahedron Lett 38:4769–4772 and Duvold, et al. (1997) Tetrahedron Lett 38:6181–6184) adapted to the production of larger amounts. A solution of 3-methyl-2(5H)-furanone (200 mg, 2 mmol) in dry ether (20 ml) was added at 0° C. over a period of 15 min to a stirred suspension of LiAIH4 (46 mg, 1.2 mmol) in dry ether (20 ml) under argon. The reaction mixture was stirred at 0° C. for further 2 h. A saturated solution of NH4CI (2 ml) was slowly added until the excess of LiAIH4 was destroyed. After acidification with a 1M HCl solution until all aluminum salts were dissolved, the aqueous phase was extracted with ethyl acetate (6×20 ml). The combined organic layers were washed with saturated brine and dried over anhydrous Na2SO4. After removal of the solvent under reduced pressure, the crude diol (177 mg) dissolved in methylene chloride (20 ml) was directly acetylated for 15 min with a mixture of acetic anhydride/triethylamine (2:3, v/v, 1 ml) in presence of catalytic amounts of dimethylaminopyridine (12 mg). Solvent and excess or reagents were evaporated under reduced pressure. Flash column chromatography (Still et al., 1978) (hexanelethyl acetate, 4:1, v/v) afforded pure diacetate (330 mg, 86%). Enantioselective dihydroxylation of diacetate (300 mg, 1.6 mmol) was performed by stirring at 0° C. in terbutanol/water (1:1, v/v, 6 ml) in the presence of the chiral osmylation reagent AD-mix-b (2.5 g) and CH3SO2NH2 (152 mg, 1.6 mmol). After 24 hours, the reaction was quenched with solid Na2SO3 and additional stirring for 30 minutes. Repeated extraction with ethyl acetate (6×20 ml) and flash chromatography (ethyl acetate) afforded a mixture only containing 2-C-methyl-D-erythritol diacetates (resulting from partial intramolecular transesterifications) (312 mg, 88% yield). Quantitative deacetylation was performed overnight at room temperature in the presence of basic Amberlyst A-26 (OH— form) (150 mg for 1 mmol) in methanol (30 ml) (Reed et al., 1981) Filtration of the resin and evaporation of the solvent directly afforded pure 2-C-methyl-D-erythritol (1 90 mg, 75% overall yield).

Provenance & Evidence