激进的氯二氟甲基化：为（杂）芳烃多样化提供了一种模式。
Radical Chlorodifluoromethylation: Providing a Motif for (Hetero)arene Diversification.
机构信息
Willard Henry Dow Laboratory, Department of Chemistry , University of Michigan , 930 North University Avenue , Ann Arbor , Michigan 48109 , United States.
出版信息
Org Lett. 2018 Jun 15;20(12):3491-3495. doi: 10.1021/acs.orglett.8b01249. Epub 2018 Jun 1.
Abstract
A method for the radical chlorodifluoromethylation of (hetero)arenes using chlorodifluoroacetic anhydride is reported. This operationally simple protocol proceeds under mild photochemical conditions with high functional group compatibility and complements the large body of literature for the trifluoromethylation of (hetero)arenes. Introduction of the chlorodifluoromethyl motif enables rapid diversification to a wide array of aromatic scaffolds. This work showcases the chlorodifluoromethyl group as an attractive entryway to otherwise synthetically challenging electron-rich difluoromethyl(hetero)arenes. Furthermore, facile conversion of the CFCl moiety into the corresponding aryl esters, gem-difluoroenones, and β-keto-esters is demonstrated.
摘要
本文报道了一种使用氯二氟乙酸酐对（杂）芳环进行自由基氯二氟甲基化的方法。该操作简单的方法在温和的光化学反应条件下进行，具有高官能团相容性，补充了大量关于（杂）芳环三氟甲基化的文献。氯二氟甲基化基序的引入使得快速多样化到广泛的芳基支架成为可能。这项工作展示了氯二氟甲基作为一种有吸引力的方法，可以合成具有挑战性的富电子二氟甲基（杂）芳基。此外，还证明了 CFCl 部分很容易转化为相应的芳基酯、偕二氟烯酮和β-酮酯。
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Org Lett. 2018 Jun 15;20(12):3491-3495. doi: 10.1021/acs.orglett.8b01249. Epub 2018 Jun 1.
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本文引用的文献
1
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Angew Chem Int Ed Engl. 2017 Nov 20;56(47):15073-15077. doi: 10.1002/anie.201709487. Epub 2017 Oct 24.
2
The Direct C-H Difluoromethylation of Heteroarenes Based on the Photolysis of Hypervalent Iodine(III) Reagents That Contain Difluoroacetoxy Ligands.基于含有二氟乙酰氧基配体的高价碘(III)试剂的光解实现杂芳环的直接 C-H 二氟甲基化反应。
Org Lett. 2017 Oct 6;19(19):5126-5129. doi: 10.1021/acs.orglett.7b02416. Epub 2017 Sep 12.
3
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J Am Chem Soc. 2017 Jul 12;139(27):9325-9332. doi: 10.1021/jacs.7b04457. Epub 2017 Jun 27.
4
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5
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6
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7
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Chem Rev. 2016 Jan 27;116(2):422-518. doi: 10.1021/acs.chemrev.5b00392. Epub 2016 Jan 12.
10
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