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Enantioselective Synthesis of “NO<sub>2</sub>···NH” Hydrogen Bond-Stabilized C–N Axially Chiral Diarylamines

Wei Lin, Yingbo Shao, Zeyang Hao, Zilu Huang, Zhiyuan Ren, Li Chen, Xin Li

2024ACS Catalysis15 citationsDOI

Abstract

Herein, N -nucleophilic tandem oxidation– N -arylation–oxidation reaction and C -nucleophilic bromination reaction of substituted anilines have been developed using chiral phosphoric acid catalysis, enabling access to axially chiral diarylamines. The key feature of this strategy is that the “NO 2 ···H–N” hydrogen bond was successfully introduced into acyclic diaryl secondary amines, which contain two potential contiguous atropisomeric C–N axes, to stabilize one of the planar axial conformations. This methodology provided a series of optically pure diarylamine atropisomers containing this new hydrogen bond type in good yields (up to 99%) and high enantiomeric ratios (up to 99.5:0.5 e.r.). The synthetic utility was demonstrated through large-scale reactions and transformations of the products. Plausible models were proposed to explain the enantioselectivity of the products.

Topics & Concepts

AtropisomerEnantioselective synthesisChemistryNucleophileCatalysisHydrogen bondEnantiomerAxial chiralityCombinatorial chemistryPhosphoric acidMedicinal chemistryStereochemistryOrganic chemistryMoleculeAxial and Atropisomeric Chirality SynthesisMolecular spectroscopy and chiralityNonlinear Waves and Solitons
Enantioselective Synthesis of “NO<sub>2</sub>···NH” Hydrogen Bond-Stabilized C–N Axially Chiral Diarylamines | Litcius