Total syntheses of (-)-mesembrane and (-)-mesembrine via palladium-catalyzed enantioselective allylic substitution and zirconium-promoted cyclization
Total syntheses of (-)-mesembrane and (-)-mesembrine via palladium-catalyzed enantioselective allylic substitution and zirconium-promoted cyclization
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DOI：
10.1021/jo9701187
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发表时间：
1997-05-16
影响因子：
3.6
通讯作者：
Sato, Y
中科院分区：
文献类型：
--
作者：
Mori, M;Kuroda, S;Sato, Y
以氮上保护基团较大的2-芳基环己烯基烯胺衍生物4为原料，采用锆促进环化法合成了4-芳基六氢吲哚衍生物5。4e与Cp2ZrBu2反应，然后用MeMgBr和O-2处理，由于芳基阻止了Oz接近锆，因此在一锅反应中得到了产率63%的2a。（+/-）-膜和(+/-)-膜从2a开始全合成。为了以手性形式合成这些天然产物，在(S)-BINAPO为手性配体的情况下，以碳酸烯丙基22a和n -托基烯丙胺23为原料，采用钯催化的不对称胺化反应制备了烯丙胺衍生物24（产率80%，ee 86%，甲醇重结晶，ee 99%，回收率79%）。由该烯丙胺合成(-)-膜膜和(-)-膜膜。
4-Arylhexahydroindole derivatives 5 were synthesized from 2-arylcyclohexenyl allylamine derivatives 4, which have a large protecting group on nitrogen, using zirconium-promoted cyclization. Reaction of 4e with Cp2ZrBu2, followed by treatment with MeMgBr and then O-2, gave 2a in 63% yield by a one-pot reaction, since the approach of Oz to zirconium was prevented by the aryl group. The total syntheses of (+/-)-mesembrane and (+/-)-mesembrine were achieved starting from 2a. To synthesize these natural products in a chiral form, the starting allylamine derivative 24 (80% yield, 86% ee, recrystallized from MeOH, 99% ee with 79% recovery) was prepared from allyl carbonate 22a and N-tosylallylamine 23 using palladium-catalyzed asymmetric amination in the presence of (S)-BINAPO as a chiral ligand. (-)-Mesembrane and (-)-mesembrine were synthesized from this allylamine 24.