SSG 1.4 Arrested Development Page
| " Okay, Lindsay, are you forgetting that I was a professional twice over— an analyst and a therapist. The world’s first analrapist." -Tobias | ||
Experimental
Diene 118
Freshly cut sodium (1.15 g, 50.0 mmol) was added to a solution of naphthalene (6.20 g, 50.0 mmol) in DME (100 mL). The mixture was stirred for 1 h and the clear, colorless mixture became a dark green solution. Sulfonamide 116 (5.60 g, 7.40 mmol) was dried by azeotropic distillation of benzene (3 x 14 mL). The resulting residue was dissolved in THF (75 mL) and cooled to –78 ºC. The solution of sodium naphthalide was added dropwise to the sulfonamide solution until the dark green color persisted and TLC analysis indicated complete consumption of the sulfonamide. Saturated aqueous NaHCO3 (50 mL) was added rapidly and the resulting cloudy colorless suspension was allowed to warm to room tempaterure (50 mL) was added and the mixture was extracted with EtOAc (3 x 100 mL). The combined organic extracts were washed with brine (1 x 50 mL), dried over MgSO4, and concentrated under reduced pressure. Purification by flash chromatography (1:10 EtOAc:hex then, 1:5 EtOAc:hex) to gave amine 117 as a viscous, colorless oil (3.77 g, 6.20 mmol, 84%) that yellowed upon exposure to air. The product was carried on immediately. In one portion, NaBH3CN (3.10 g, 49.6 mmol) was added to a stirred suspension of amine 117 (3.77 g, 6.2 mmol), 6-hepten-1-al (1.7 mL, 12.4 mmol), powdered 4 Å mol sieves (3.10 g) and acetic acid (0.73 mL, 12.4 mmol) in MeCN (62 mL). The suspension was stirred for 10 min and a second portion of 6-hepten-1-al (1.7 mL, 12.4 mmol) was added. The suspension was stirred for an additional 15 min. The reaction mixture was poured into saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (3 x 100 mL). The combined organic extracts were washed with brine (1 x 50 mL), dried over MgSO4, and concentrated under reduced pressure. Purification by flash chromatography (EtOAc:hex, 1:10) gave a mixture of diene 118 and an unidentified byproduct. The residue was further purified by flash chromatography (1:9 EtOAc:benzene) to give diene 118 as a colorless oil.