Divergent Strain-Release Amino-Functionalization of [1.1.1]Propellane with Electrophilic Nitrogen-Radicals
Divergent Strain-Release Amino-Functionalization of [1.1.1]Propellane with Electrophilic Nitrogen-Radicals
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DOI：
10.1002/anie.202000140
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发表时间：
2020-02-26
影响因子：
16.6
通讯作者：
Leonori, Daniele
中科院分区：
文献类型：
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作者：
Kim, Ji Hye;Ruffoni, Alessandro;Leonori, Daniele
在这里，我们报道了一种光催化策略的发展，以发散制备功能化的双环[1.1.1]戊胺。这种方法首次利用了氮自由基与[1.1.1]螺旋桨发生应变释放反应的能力。这些开壳中间体的亲电性质和在C-N键形成/开环的过渡态中存在的强极性效应促进了这种反应。借助于简单的还原猝灭光氧化还原循环，我们成功地利用了这种新的自由基应变释放胺化作用，作为与几种外部捕捉剂兼容的多组份级联的一部分。总体而言，这种激进的策略使得能够快速构建新的氨基功能化构建块，在药物化学项目中具有潜在的应用，如p-取代的苯胺生物等位体。
Herein we report the development of a photocatalytic strategy for the divergent preparation of functionalized bicyclo[1.1.1]pentylamines. This approach exploits, for the first time, the ability of nitrogen-radicals to undergo strain-release reaction with [1.1.1]propellane. This reactivity is facilitated by the electrophilic nature of these open-shell intermediates and the presence of strong polar effects in the transition-state for C-N bond formation/ring-opening. With the aid of a simple reductive quenching photoredox cycle, we have successfully harnessed this novel radical strain-release amination as part of a multicomponent cascade compatible with several external trapping agents. Overall, this radical strategy enables the rapid construction of novel amino-functionalized building blocks with potential application in medicinal chemistry programs as p-substituted aniline bioisosteres.