Room Temperature Construction of Vicinal Amino alcohols via Electroreductive Cross-coupling of N-Heteroarenes and Carbonyls

Maorui Wang,^† Chengqian Zhang,^† Chenggang Ci, ^*,ǂ Huanfeng Jiang,^† Pierre. H. Dixneuf,^‡ and Min Zhang^*,†

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.

J. Am. Chem. Soc., 2023, Doi:org/10.1021/jacs.3c02776