Catalytic Atroposelective Synthesis of N-Aryl Quinoid Compounds
Catalytic Atroposelective Synthesis of N-Aryl Quinoid Compounds
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DOI：
10.1021/jacs.9b12994
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发表时间：
2020-02-05
影响因子：
15
通讯作者：
Gustafson, Jeffrey L.
中科院分区：
文献类型：
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作者：
Vaidya, Sagar D.;Toenjes, Sean T.;Gustafson, Jeffrey L.
二芳基胺和相关支架是现代药物发现中最常见的化学类型之一。虽然它们可能拥有两个手性轴，但还没有对其对映选择性合成的研究，因为这些轴通常具有较低的立体化学稳定性。在此，我们报道了手性磷酸催化 N-芳基醌类化合物（一类类似于二芳基胺的化合物）的亲电选择性卤化。这种化学反应以优异的产率和对映选择性产生大量立体化学稳定的 N-芳基醌。这项工作代表了二芳基胺样支架的天体选择性合成的第一个例子，并将成为对这些普遍存在的手性支架的手性进行基础和应用研究的门户。
Diarylamines and related scaffolds are among the most common chemotypes in modern drug discovery. While they can potentially possess two chiral axes, there are no studies on their enantioselective synthesis, as these axes typically possess lower stereochemical stabilities. Herein, we report a chiral phosphoric acid catalyzed atroposelective electrophilic halogenation of N-aryl quinoids, a class of compounds that are analogous to diarylamines. This chemistry yields a large range of stereochemically stable N-aryl quinoids in excellent yields and atroposelectivity. This work represents the first example of the atroposelective synthesis of a diarylamine-like scaffold and will serve as a gateway to fundamental and applied studies on the scarcely studied chirality of these ubiquitous chiral scaffolds.