Department of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis, Minnesota 55455, USA.
Nat Chem. 2017 Jun;9(6):523-530. doi: 10.1038/nchem.2732. Epub 2017 Feb 27.
An important question in organic chemistry concerns the extent to which benzynes-one of the classical reactive intermediates in organic chemistry-can react in discriminating fashion with trapping reagents. In particular, whether these species can react selectively with substrates containing multiple functional groups and possible sites of reactivity has remained unanswered. Natural products comprise a palette of multifunctional compounds with which to address this question. Here, we show that benzynes produced by the hexadehydro-Diels-Alder (HDDA) reaction react with many secondary metabolites with a preference for one among several pathways. Examples demonstrating such selectivity include reactions with: phenolics, through dearomatizing ortho-substitution; alkaloids, through Hofmann-type elimination; tropolone and furan, through cycloaddition; and alkaloids, through three-component fragmentation-coupling reactions. We also demonstrate that the cinchona alkaloids quinidine and quinine give rise to products (some in as few as three steps) that enable subsequent and rapid access to structurally diverse polyheterocyclic compounds. The results show that benzynes are quite discriminating in their reactivity-a trait perhaps not broadly enough appreciated.
在有机化学中，一个重要的问题是苯炔——这是有机化学中经典的反应中间体之一——在多大程度上可以以有区别的方式与捕获试剂反应。特别是，这些物质是否可以选择性地与含有多个官能团和可能的反应位点的底物反应，这一问题仍然没有得到解答。天然产物包含了一系列多功能化合物，可以用来解决这个问题。在这里，我们表明，通过十六氢化二苯并环庚烯（HDDA）反应生成的苯炔与许多次级代谢产物反应，对几种途径中的一种具有优先选择性。例如，反应包括：与酚类化合物通过去芳构化邻位取代；与生物碱类化合物通过 Hofmann 型消除；与三唑和呋喃通过环加成；与生物碱类化合物通过三组分断片-偶联反应。我们还表明，金鸡纳生物碱奎宁和奎尼丁产生的产物（有些只需三步）可以随后快速获得结构多样的多杂环化合物。结果表明，苯炔在反应性方面具有很强的选择性——这一特性可能没有得到足够广泛的认识。
