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Atroposelective Synthesis of N‐Arylated Quinoids by Organocatalytic Tandem N‐Arylation/Oxidation

Chang‐Qiu Guo, Chuan‐Jun Lu, Li‐Wen Zhan, Peng Zhang, Qi Xu, Jia Feng, Renrong Liu

2022Angewandte Chemie International Edition28 citationsDOI

Abstract

Diarylamines and related scaffolds are ubiquitous atropisomeric chemotypes in biologically active natural products. However, the catalytic asymmetric synthesis of these axially chiral compounds remains largely unexplored. Herein, we report that a BINOL-derived chiral phosphoric acid (CPA) successfully catalyzed the atroposelective coupling of quinone esters and anilines through direct C-N bond formation to afford N-aryl quinone atropisomers with an unprecedented intramolecular N-H-O hydrogen bond within a six-membered ring in good yields and enantioselectivities with the quinone ester as both the electrophile and the oxidant. A gram-scale experiment demonstrated the utility of this synthetic protocol. Moreover, this methodology provides a platform for the synthesis of structurally diverse secondary amine atropisomers by nucleophilic addition.

Topics & Concepts

TandemChemistryCombinatorial chemistryOrganocatalysisOrganic chemistryCatalysisEnantioselective synthesisEngineeringAerospace engineeringAxial and Atropisomeric Chirality SynthesisMolecular spectroscopy and chiralitySphingolipid Metabolism and Signaling
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