Experimental

Hover your mouse over the superscript numbers to view the corresponding footnotes.

Molecule 4 (1.07 g, 2.11 mmol) was treated with 2,4,4,6-tetrabromo-2,5-cyclohexadienone ¹ (1.73 g, 4.22 mmol) in 1,2-dichloroethane (21.1 ml) at 0 °C and stirred for 30 minutes to yield the intermediate 7, as a mixture of two diastereomers. EtOH (21.1 ml) was added followed immediately by NaBH₄ ² (399 mg, 10.5 mmol) to form the cis-fused hydroxy pyrrolidine 8 and heated to 50 °C ³ for one hour to form the intermediate 10. Reaction mixture was quenched in 1:1 5% aqueous NaHCO₃/brine ⁴ (100 ml), and extracted with CH₂Cl₂ ⁵ (3 x 100 ml). The organics were dried over MgSO₄ ⁶, filtered, concentrated, and diluted with EtOH (14.0 ml). Intermediate 10 was heated to reflux and indium powder ⁷ (484 mg, 4.22) was added, followed by saturated aqueous NH₄Cl (7.0 ml). After 3.5 hours, the solution was cooled and diluted with EtOAc (100 ml) and 5% aqueous NaHCO₃ ⁸ (100 ml). The aqueous layer was extracted ⁹ with EtOAc (3 x 100 ml) and the combined organics were dried over MgSO₄ ¹⁰, filtered and concentrated. The products were separated by flash chromatography ¹¹ (silica gel, 4:1 → 2:1 hexanes/EtOAc). The amine 3 came out as a white foam.