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Enhanced Pyridine-Oxazoline Ligand-Enabled Pd(II)-Catalyzed Aminoacetoxylation of Alkenes for the Asymmetric Synthesis of Biaryl-Bridged 7-Membered <i>N</i>-Heterocycles and Atropisomers

Beibei Guo, Xiaoyang Yan, Zicong Wang, Chen Shen, Weifu Chen, Shouyi Cen, Qian Peng, Zhipeng Zhang

2025Journal of the American Chemical Society8 citationsDOI

Abstract

A new class of binaphthyl unit-enhanced pyridine-oxazoline ligands was developed to promote the Pd-catalyzed enantioselective intramolecular 7- exo aminoacetoxylation of unactivated biaryl alkenes. Biaryl-bridged 7-membered N -heterocycles bearing a chiral center were obtained in good yields with excellent enantioselectivities (up to 99:1 er). Computational investigations on a series of biaryl-bridged 7-membered rings provided insights into the rotational barrier of the potentially chiral biaryl unit by the substituent effect including the heteroatom, the protecting group, and the chiral center. The kinetic resolution of racemic axially chiral biaryls via intramolecular enantioselective aminoacetoxylation of alkenes has also been achieved, affording previously inaccessible biaryl-bridged 7-membered N -heterocycles bearing both a chiral center and a chiral axis, as well as axially chiral biaryl amino alcohols.

Topics & Concepts

ChemistryAtropisomerOxazolineEnantioselective synthesisIntramolecular forceAxial chiralityKinetic resolutionPyridineRacemizationStereochemistrySubstituentLigand (biochemistry)Combinatorial chemistryCatalysisMedicinal chemistryOrganic chemistryBiochemistryReceptorAxial and Atropisomeric Chirality SynthesisAlkaloids: synthesis and pharmacologyMolecular spectroscopy and chirality
Enhanced Pyridine-Oxazoline Ligand-Enabled Pd(II)-Catalyzed Aminoacetoxylation of Alkenes for the Asymmetric Synthesis of Biaryl-Bridged 7-Membered <i>N</i>-Heterocycles and Atropisomers | Litcius