Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Org Chem. 2009 Dec 18;74(24):9292-304. doi: 10.1021/jo901926z.
We report our full account of the enantioselective total synthesis of (-)-acylfulvene (1) and (-)-irofulven (2), which features metathesis reactions for the rapid assembly of the molecular framework of these antitumor agents. We discuss (1) the application of an Evans Cu-catalyzed aldol addition reaction using a strained cyclopropyl ketenethioacetal, (2) an efficient enyne ring-closing metathesis cascade reaction in a challenging setting, (3) the reagent IPNBSH for a late-stage reductive allylic transposition reaction, and (4) the final RCM/dehydrogenation sequence for the formation of (-)-acylfulvene (1) and (-)-irofulven (2).
我们报告了 (-)-酰基fulvene (1) 和 (-)-irofulven (2) 的对映选择性全合成的完整描述，该合成采用了复分解反应，快速构建了这些抗肿瘤药物的分子骨架。我们讨论了：（1）使用应变环丙基酮硫缩醛的 Evans Cu 催化的Aldol 加成反应的应用；（2）在具有挑战性的条件下高效的烯炔环 closing metathesis 级联反应；（3）试剂 IPNBSH 用于晚期还原烯丙基反式置换反应；（4）(-)-酰基 fulvene (1) 和 (-)-irofulven (2) 的最终 RCM/脱氢序列的形成。
