Room Temperature Construction of Vicinal Amino Alcohols via Electroreductive Cross-Coupling of N-Heteroarenes and Carbonyls

Maorui Wang; Chengqian Zhang; Chenggang Ci; Huanfeng Jiang; Pierre H Dixneuf; Min Zhang

doi:10.1021/jacs.3c02776

Room Temperature Construction of Vicinal Amino Alcohols via Electroreductive Cross-Coupling of N-Heteroarenes and Carbonyls

J Am Chem Soc. 2023 May 24;145(20):10967-10973. doi: 10.1021/jacs.3c02776. Epub 2023 Apr 19.

Authors

Maorui Wang¹, Chengqian Zhang¹, Chenggang Ci², Huanfeng Jiang¹, Pierre H Dixneuf³, Min Zhang¹

Affiliations

¹ Key Lab of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, China.
² Key Laboratory of Computational Catalytic Chemistry of Guizhou Province, Department of Chemistry and Chemical Engineering, Qiannan Normal University for Nationalities, Duyun 558000, China.
³ Univ. Rennes, CNRS, ISCR UMR 6226, 35000 Rennes, France.

PMID: 37075201
DOI: 10.1021/jacs.3c02776

Abstract

Despite the widespread applications of α-hydroxyalkyl cyclic amines, direct and diverse access to such a class of unique vicinal amino alcohols still remains, to date, a challenge. Here, through a strategy of electroreductive α-hydroxyalkylation of inactive N-heteroarenes with ketones or electron-rich arylaldehydes, we describe a room temperature approach for the direct construction of α-hydroxyalkyl cyclic amines, which features a broad substrate scope, operational simplicity, high chemoselectivity, and no need for pressurized H₂ gas and transition metal catalysts. The zinc ion generated from anode oxidation plays a crucial role in the activation of both reactants by decreasing their reduction potentials. The strategy of electroreduction in combination with substrate activation by Lewis acids in this work is anticipated to develop more useful transformations.