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

人们已经做出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度，而且考虑到它们作为多功能合成构筑块的用途。串联还原偶合-狄克曼缩合反应是从丙烯酸酯衍生物(α，β-不饱和酯)有效地合成草环戊烷羧酸盐的一步法。肉桂酸衍生物的电加氢二聚和金属诱导环化是常用的方法，但还没有一种方法能以分子内方式生成双环恶环戊烷羧酸盐。以简单的双α，β-不饱和酯为原料，在微量甲醇存在下，用一种电子转移试剂SMI_2，建立了一种有效、直接的一步法合成双环[4.3.0]壬烷-8-酮和双环[3.3.0]辛烷-3-酮。该反应还合成了严重应变的双环[3.3.0]辛烷翘曲反环体系和三环酮酸酯，但没有生成双环[5.3.0]十一烷-9-酮和双环[6.3.0]十一烷-10-酮。为了制备这些体系，1，2-环丁二酸二羧酸酯通过Sm(II)诱导的顺序还原裂解-Dieckmann缩合反应被开发出来，该反应很容易从相应的环烯或丙烯酸酯衍生物中获得。该反应是环丁烷通过串联还原裂解-Dieckmann缩合转化为环戊烷的第一个实例。在此基础上，以Sm(II)诱导的丙烯酸酯类化合物环化反应为关键步骤，完成了三喹烷型倍半萜、水飞蓟烯、榄香型倍半萜、Eleman-8β、12-Olide的正式全合成和赤霉素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.