Generation and Alkylation of α-Carbamyl Radicals via Organic Photoredox Catalysis
Generation and Alkylation of α-Carbamyl Radicals via Organic Photoredox Catalysis
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DOI：
10.1021/jacs.8b04890
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发表时间：
2018-07-25
影响因子：
15
通讯作者：
Nicewicz, David A.
中科院分区：
文献类型：
--
作者：
McManus, Joshua B.;Onuska, Nicholas P. R.;Nicewicz, David A.
胺的直接C-H功能化策略是有价值的，因为这些化合物包括许多药物，农用化学品和天然产物。这项工作描述了一种新的方法，通过光氧化还原催化产生的a-氨基甲酰自由基，对氨基甲酸酯保护的仲胺进行C-H功能化。使用高氧化性的有机吖啶光氧化还原催化剂，可以直接氧化具有高氧化还原电位的氨基甲酸酯保护胺，从而得到相应的氨基甲酸酯阳离子自由基。在去质子化之后，得到的开壳物质可以被各种迈克尔受体截获，得到精细的α功能化仲胺。该反应在温和的条件下进行，不需要外源氧化还原介质或底物预功能化。此外，我们能够通过对映选择性合成吲哚嗪类生物碱(+)-单茅碱I来展示这种方法的实用性。
Strategies for the direct C-H functionalization of amines are valuable as these compounds comprise a number of pharmaceuticals, agrochemicals and natural products. This work describes a novel method for the C-H functionalization of carbamate-protected secondary amines via a-carbamyl radicals generated using photoredox catalysis. The use of the highly oxidizing, organic acridinium photoredox catalyst allows for direct oxidation of carbamate-protected amines with high redox potentials to give the corresponding carbamyl cation radical. Following deprotonation, the resultant open-shell species can be intercepted by a variety of Michael acceptors to give elaborate alpha-functionalized secondary amines. The reaction proceeds under mild conditions without the requirement of exogenous redox mediators or substrate prefunctionalization. Additionally, we were able to showcase the utility of this methodology through the enantioselective synthesis of the indolizidine alkaloid, (+)-monomorine I.