Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids
Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids
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DOI：
10.1002/anie.202001824
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发表时间：
2020-06-02
影响因子：
16.6
通讯作者：
Scheidt, Karl A.
中科院分区：
文献类型：
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作者：
Bay, Anna V.;Fitzpatrick, Keegan P.;Scheidt, Karl A.
作为构建复杂有机支架的关键元素，C-C键的形成一直是合成有机化学领域的一大挑战。单电子化学的最新进展使形成各种C-C键的新方法成为可能。本发明公开了一种新的单电子还原酰基氮杂环芳烃的方法，用于从羧酸生成酮。N-杂环卡宾(NHC)和光氧化还原催化相结合，实现了酰基氮杂环的原位构筑和自由基-自由基偶联。在各种药物化合物的后期官能化中，该方案在合成中的实用性得到了展示。使用手性NHC的初步研究表明，可以实现对映体选择性，这显示了该协议相对于替代方法的优势。
As a key element in the construction of complex organic scaffolds, the formation of C-C bonds remains a challenge in the field of synthetic organic chemistry. Recent advancements in single-electron chemistry have enabled new methods for the formation of various C-C bonds. Disclosed herein is the development of a novel single-electron reduction of acyl azoliums for the formation of ketones from carboxylic acids. Facile construction of the acyl azolium in situ followed by a radical-radical coupling was made possible merging N-heterocyclic carbene (NHC) and photoredox catalysis. The utility of this protocol in synthesis was showcased in the late-stage functionalization of a variety of pharmaceutical compounds. Preliminary investigations using chiral NHCs demonstrate that enantioselectivity can be achieved, showcasing the advantages of this protocol over alternative methodologies.