Development of useful sequential cyclization of acrylate derivatives and applications to bioactive natural products synthesis

已经进行了许多努力来生产双环环戊酮，不仅考虑到它们在自然界中的丰富性，而且考虑到它们作为通用合成结构单元的有用性。已经发现串联还原偶联-Dieckmann缩合反应作为从丙烯酸酯衍生物（α，β-不饱和酯）有效地生产氧杂环戊烷羧酸酯的一步法是非常有用的。肉桂酸酯衍生物的电氢化二聚和金属诱导的环化是通常用于此目的的方法，但没有一种方法显示出以分子内方式产生双环氧杂环戊烷羧酸酯。本文建立了在微量甲醇存在下，用SmI_2作电子转移试剂，由简单的双-α，β-不饱和酯直接一步合成双环[4.3.0]壬-8-酮和双环[3.3.0]辛-3-酮的方法。反应还合成了严重张力的双环[3.3.0]辛烷弯曲反环体系和三环酮酯，但没有生成双环[5.3.0]癸-9-酮和双环[6.3.0]十一烷-10-酮。为了制备这些系统，新的扩环反应的1，2-环丁烷二羧酸酯，容易从相应的环烯烃或丙烯酸酯衍生物，通过Sm（II）诱导的顺序还原断裂-Dieckmann缩合开发。该反应是环丁烷通过串联还原断裂-Dieckmann缩合转化为环戊烷的第一个实例。以碘化钐诱导的丙烯酸酯衍生物环化反应为关键步骤，进行了苯醌型倍半萜、水蛭烯、榄香烯型倍半萜、榄香烯-8 β，12-内酯的全合成和赤霉素A_1的全合成。

Numerous efforts have been made to produce bicyclic cyclopentanones, not only in consideration of their abundance in nature, but also their usefulness as versatile synthetic building blocks. The tandem reductive coupling-Dieckmann condensation reaction has been found quite useful as a one-step process for effectively producing oxacyclopentanecarboxylates from acrylate derivatives (α,β-unsaturated esters). Electrohydrodimerization and metal-induced cyclization of cinnamate derivatives are methods generally applied for this purpose but to none has been shown to produce in an intramolecular manner bicyclic oxacyclopentanecarboxylate. The authors established an effective and direct one-step process for obtaining bicyclo[4.3.0]nonan-8-ones and bicyclo[3.3.0]octan-3-ones from simple bis-α,β-unsaturated esters using one electron transfer reagent SmI_2 in the presence of methanol in trace amount. Severely strained bicyclo[3.3.0]octane warped trans ring system and tricyclic keto esters were also synthesized by the reaction, but the formation of bicyclo[5.3.0]decan-9-ones and bicyclo[6.3.0]undecan-10-ones failed to occur. For the preparation of these system, the novel ring-expansion reaction of 1,2-cyclobutanedicarboxylates, readily accessible from the corresponding cycloalkenes or acrylate derivatives, via Sm(II)-induced sequential reductive fragmentation-Dieckmann condensation was developed. This reaction is the first instance of the transformation of cyclobutanes to cyclopentanes via tandem reductive fragmentation-Dieckmann condensation. Forthermore, the formal total syntheses of triquinane-type sesquiterpines, hirustene, and eleman-type sesquiterpenoid, eleman-8β,12-olide, and the total synthesis of gibberellin A_1 were conducted with Sm(II) iodide-induced cyclization of acrylate derivatives as key steps.