Recently, stannyl anion has become a useful synthetic tool for organic synthesis. We have developed various cyclization using stannyl anion, generated from Me_3SiSnBu_3 and F^-. Cephalotaxine (28), the major alkaloid of C.harringtonia, has a unique skeleton, which has potential pharmacological activity, such as antileukemia activity. In order to synthesize (-)-cephalotaxine (28), we planned on the basis of the following points. The unique skeleton, 1-azaspiro[4.4]nonane moiety fused benzazepine system, would be prepared by the reaction of 44 with stannyl anion generated from Me_3SiSnBu_3 and F^-. For the synthesis of optically active cephalotaxine, the optically pure starting material 44 would be obtained from D-(+)-proline via 36 by Seebach's procedure. The methylenedioxy group on the aromatic ring is not favorable for the cyclization of the seven membered ring. From (D)-proline, we could obtain compound 44 as an optically active form. To a DMF solution of 44 and CsF was added Me_3SiSnBu_3 (2.0 eq.) at 0℃ and the solution was stirred at room temperature for 8 h. After usual work up, desired cyclized products 45 and 46, were obtained in 85% and 3% yields, respectively. Compound 46 was easily converted into 45 by treatment with Bu_4NF in good yield. Reaction of 45 with PPA followed by treatment with BBr_3 and then CH_2Br_2 gave 47. Treatment of 47 with OsO_4 in the presence of trimethylamine N-oxide in AcOH afforded the diol, which was oxidized with DMSO and trifluoroacetic anhydride to give diketone 48. A dioxane solution of 48 and dimethozypropane in the presence of TsOH was refluxed for 8 h to give 49. The spectral data of cephalotaxinone (49) was fully identical with those of the product reported^<6a>, but it was a racemic product [α]_D-8.2°(c, 0.4, EtOH), lit. [α]_D-135° (c 0.95, EtOH)]. Thus, 48 was treated with methyl orthoformate in the presence of TsOH in CH_2Cl_2 to give 49 in 47% yield with 88% ee. Finally, treatment of 49 with NaBH_4 in MeOH provided (-)-cephalotaxine.
