Tetrahydrofuran → (S)-3-(1,3-Benzodioxol-5-yl)-2,3-dihydro-6-propoxy-1H-inden-1-one

Participants

Reaction Conditions

Reaction Steps

A 250 mL three-necked flask equipped with air driven stirrer and 250 mL addition funnel was charged with anhydrous THF (50 mL) and (R)-MeCBS (1.6 mL, 1 M, 1.6 mmol). The solution was cooled to −15° C. and BH3-THF (32.4 mL, 1 M, 32.4 mmol) added in a steady stream. Charge the 250 mL addition funnel with 3-(1,3-Benzodioxol-5-yl)-6-propoxy-1H-inden-1-one (10 g, 32.4 mmol) and anhydrous THF (50 mL) and add the solution dropwise over 1.5 h period while maintaining the internal reaction temperature between −10 to −15° C. Upon complete addition, stir the reaction mixture for 0.5 h at −15° C., cool the solution to −25° C. and add CH3OH (20 mL) dropwise over 20 minutes while maintaining the internal reaction temperature below −15° C. Warm the solution to 20° C. over 0.5 h and stir the solution for an additional 0.5 h at ambient temperature. Cool the solution to 0° C. and add Et3N (1 mL, 81 mmol) to the reaction mixture dropwise over 15 minutes while maintaining the internal reaction temperature below 5° C. Add 1,1-bis(triphenylphosphine) nickel(II) chloride (211 mg, 3.24 mmol) and warm the reaction mixture to 60° C. for 4 h. Concentrate the solution to 1/4 volume, cool to room temperature, add Celite (12 g) and then hexanes (85 ml). Stir the mixture vigorously for 10 min and filter through a SiO2 (10 g) and Celite (10 g) pad. Wash the filter pad with THF/hexane (45 mL/120 mL), combine the filtrates, and transfer to a 500 mL round-bottomed flask. Concentrate the solution in vacuo until a precipitate forms, add hexane (40 mL) and cool the solution to −15 CC for 8 h. Filter the precipitate, wash the filter cake with cold (0° C.) hexane solution and dry under vacuum to afford (S)-3-(1,3-Benzodioxol-5-yl)-2,3-dihydro-6-propoxy-1H-inden-1-one as a light yellow solid (8.1 g, 81%, 88% e.e.): mp 68.0-69.5° C.

Provenance & Evidence