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Nitrosobenzene‐Enabled Chiral Phosphoric Acid Catalyzed Enantioselective Construction of Atropisomeric <i>N</i>‐Arylbenzimidazoles

Qian‐Jin An, Wang Xia, Wei‐Yi Ding, Huanhuan Liu, Shao‐Hua Xiang, Yong‐Bin Wang, Guofu Zhong, Bin Tan

2021Angewandte Chemie International Edition70 citationsDOI

Abstract

Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N-arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed to transform two classes of 2-naphthylamine derivatives into structurally diverse N-arylbenzimidazole atropisomers with excellent chemo- and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C-N bond formation while the resulting amine performs the nucleophilic addition to form the second C-N bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N-arylbenzimidazoles for their potential utilities in asymmetric catalysis.

Topics & Concepts

NitrosobenzeneEnantioselective synthesisPhosphoric acidCatalysisChemistryOrganic chemistryAxial and Atropisomeric Chirality SynthesisMolecular spectroscopy and chiralityAsymmetric Synthesis and Catalysis