Diisopropylamine → Lithium diisopropylamide mono(tetrahydrofuran)

Participants

Reaction Conditions

Reaction Steps

LDA/THF was prepared by adding n-BuLi (0.29 mL, 1.6 M/hexanes, 0.46 mmol, 3.0 equiv) to diisopropylamine (65 μL, 0.46 mmol, 3.0 equiv) in 3 mL dry THF under a nitrogen atmosphere in a flame dried schenck flask at −78° C. The resulting solution was warmed to −20° C. and stirred for another 15 min. After the LDA solution was cooled down to −78° C., TMEDA (69 μL, 0.46 mmol, 3.0 equiv) was added slowly via a syringe. Compound S2-1-1 (0.10 g, 0.20 mmol, 1.3 equiv) was dissolved in 1 mL dry THF and added into the LDA solution slowly via a syringe. A dark-red color appeared as soon as addition started. After stirring for 10 min, enone S1-9 (74 mg, 0.15 mmol, 1.0 equiv) in 1 mL dry THF was added slowly a via syringe. After 10 min, LC/MS indicated that the enone was consumed and the product present. The reaction mixture was allowed to slowly warm to −20° C. in 1 h. A phosphate buffer solution (pH 7, 10 mL) was added, followed by the addition of 20 mL saturated aqueous ammonium chloride. The resulting mixture was extracted with dichloromethane (3×15 mL). The combined extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting orange-red oil was purified by column chromatography (Biotage 10 g column, 10% to 30% EtOAc in hexanes gradient) to yield the desired compound S2-2-1 (90 mg, 65%).

Provenance & Evidence