Radical cation-mediated annulation. Stereoselective construction of bicyclo[5.3.0]decan-3-ones by aerobic oxidation of cyclopropylamines
Radical cation-mediated annulation. Stereoselective construction of bicyclo[5.3.0]decan-3-ones by aerobic oxidation of cyclopropylamines
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DOI：
10.1021/ja017043f
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发表时间：
2001-11-14
影响因子：
15
通讯作者：
Cha, JK
中科院分区：
文献类型：
--
作者：
Lee, HB;Sung, MJ;Cha, JK
在越来越多的生物活性天然产物中发现了中等大小(七元或八元)碳环，它们通常嵌入在多环体系中。因此，开发用于构建中等尺寸碳环或将其环化到现有碳环上的通用方法已成为一个活跃的研究领域。1一类典型的含氢偶氮类天然产物已经引起了一系列优雅的合成。尽管有许多已知的方法，但值得注意的是，直接从无环底物快速组装功能化的氢唑烯的可靠方法很少。2我们设想实现分子内的Kulinkovich环丙烷3，4酯或酰胺和所得到的双环杂原子取代的环丙烷的串联扩环-环化序列，用于立体控制合成双环[5.3]。0]DeCan-3-One。后一种转化在对布克-密尔本和纳拉萨卡基团的独立研究中得到了很好的先例，这些研究涉及双环羟基环丙烷的氧化裂解和随后得到的β-酮自由基到侧链烯烃的5-外环化(方案1)。5，6我们报道了双环氨基环丙烷的类似环化反应，双环氨基环丙烷官能团被选择在各自的环丙醇底物上，因为在温和的条件下，可以调节或调节前者的氧化电位，从而容易地生成环丙胺自由基中间体。基于我们早先的观察7的另一个优点是，羧胺(特别是那些含有较大N-取代基的)的分子内Kulinkovich环丙烷化反应通常比酯的产率更高，这促使我们研究基于胺基的环化方法。
Medium-sized (seven-or eight-membered) carbocyclic rings which are typically embedded in polycyclic systems are found in an increasing number of bioactive natural products. The development of general methods for the construction of mediumsized carbocycles or their annulation onto existing carbocycles has thus become an active area of research. 1 One typical class belongs to hydroazulenic natural products which have prompted a spate of elegant syntheses. Despite many known approaches, conspicuous is the paucity of reliable methods for rapid assembly of functionalized hydroazulenes directly from acyclic substrates. 2 We envisioned the implementation of an intramolecular Kulinkovich cyclopropanation3, 4 of esters or amides and a tandem ring expansion-cyclization sequence of the resulting bicyclic heteroatom-substituted cyclopropanes for the stereocontrolled synthesis of bicyclo [5.3. 0] decan-3-ones. The latter transformation was well-precedented by independent studies of the Booker-Milburn and Narasaka groups involving oxidative cleavage of bicyclic hydroxycyclopropanes and subsequent 5-exo cyclization of the resulting β-keto radicals to the pendant olefins (Scheme 1). 5, 6 Herein we report analogous cyclization of bicyclic aminocyclopropanes.The bicyclic aminocyclopropane functionality was chosen over the respective cyclopropanol substrate because of the possibility of tuning or modulating the oxidation potential of the former for facile generation of cyclopropylaminium radical intermediates under mild conditions. An additional advantage based on our earlier observation7 that an intramolecular Kulinkovich cyclopropanation of carboxamides (especially those containing bulkier N-substituents) typically afforded higher yields than that of esters prompted us to investigate the aminium radical-based annulation approach.