Catalytic Atroposelective Synthesis of N‑Aryl Quinoid Compounds

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...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2020-02, Vol.142 (5), p.2198-2203
Main Authors: Vaidya, Sagar D, Toenjes, Sean T, Yamamoto, Nobuyuki, Maddox, Sean M, Gustafson, Jeffrey L
Format: Article
Language:English
Subjects:
Catalysis
Hydroquinones - chemical synthesis
Hydroquinones - chemistry
Stereoisomerism
Thermodynamics
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.9b12994