NiH-Catalyzed Regio- and Enantioselective Hydroalkylation for the Synthesis of β- or γ-Branched Chiral Aromatic N-Heterocycles

Ju-Song Yang; Ka Lu; Chen-Xiao Li; Zu-Hang Zhao; Fu-Min Zhang; Xiao-Ming Zhang; Yong-Qiang Tu

doi:10.1021/jacs.3c07919

NiH-Catalyzed Regio- and Enantioselective Hydroalkylation for the Synthesis of β- or γ-Branched Chiral Aromatic N-Heterocycles

J Am Chem Soc. 2023 Oct 11;145(40):22122-22134. doi: 10.1021/jacs.3c07919. Epub 2023 Sep 25.

Authors

Ju-Song Yang¹, Ka Lu¹, Chen-Xiao Li¹, Zu-Hang Zhao¹, Fu-Min Zhang¹, Xiao-Ming Zhang¹, Yong-Qiang Tu^{1

2}

Affiliations

¹ State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
² School of Chemistry and Chemical Engineering, College of Pharmaceutical Sciences, Frontier Scientific Center of Transformative Molecules, Shanghai key Laboratory of Chiral Drugs and Engineering, Shanghai Jiao Tong University, Shanghai 200240, Minhang, China.

PMID: 37749771
DOI: 10.1021/jacs.3c07919

Abstract

A nickel hydride-catalyzed regio- and enantioselective hydroalkylation reaction was developed to give access to a library of chiral β- or γ-branched aromatic N-heterocycles. This intriguing asymmetric transformation features excellent selectivities, step- and atom-economies, and generating two kinds of chiral products through one synthetic strategy. Furthermore, the possible reaction mechanism was extensively investigated using numerous control experiments and density functional theory calculations.