Trimethylsilyldiazomethane → (3aS,7aR)-Tetrahydro-2H-furo[2,3-b]pyran-5(3H)-one

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Reaction Conditions

Reaction Steps

AlMe3 (25% w/w hexanes, 250 μL, 0.6 mmol) was diluted in dry CH2Cl2 (5 mL) under argon and the solution was cooled to −78° C. A solution of ketone 28 (64 mg, 0.5 mmol) in dry CH2Cl2 (5 mL) was slowly added dropwise. After 10 min, TMSCHN2 (2 M solution in Et2O, 275 μL, 0.55 mmol) was added. The reaction was stirred for 2 h while warmed to −30° C. Saturated Rochelle's salts solution (5 mL) was added and the mixture was stirred for 1 h. The phases were separated, the aqueous phase extracted with CH2Cl2, and the combined organic phase was dried (MgSO4). The solution was filtered on a small silica gel pad, flushing with Et2O, and the collected organic phase evaporated. A crude mixture of the desired ketone along with α-silylated derivatives and isomers was then obtained. The mixture was re-dissolved in THF (5 mL). AcOH (6 drops) and TBAF (0.5 mL, 0.5 mmol) were successively added. The resulting mixture was stirred at 23° C. for 3 h and evaporated to dryness. The residue was purified by flash column chromatography on silica gel using hexanes/EtOAc (5:1) as the eluent to give ketone 29 (45 mg, 63%). TLC: Rf=0.35 (hexanes/EtOAc=2:1); 1H NMR (CDCl3, 400 MHz) δ 5.49 (d, J=6.8 Hz, 1H), 4.11 (d, J=18.2 Hz, 1H), 4.10 (m, 1H), 3.92 (d, J=18.2 Hz, 1H), 3.74 (dt, J=6.5, 8.9 Hz, 1H), 2.85 (m, 1H), 2.71 (d, J=6.3, 15.6 Hz, 1H), 2.48 (d, J=3.9, 15.6 Hz, 1H), 2.15 (m, 1H), 1.55 (ddt, J=7.7, 8.9, 12.7 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 210.7, 100.9, 67.5, 67.1, 39.2, 36.2, 31.3.

Provenance & Evidence