Reduction-interrupted Tandem Reaction for General Synthesis of Functional Amino Acids by a Heterogeneous Cobalt Catalyst

Haotian Hua, Chenggang Ci, Pierre. H. Dixneuf, Min Zhang*

Abstract: Despite the significant importance to numerous fields, the challenges in direct and diverse synthesis of γ-amino-α-hydroxybutyric acids (AHBAs) pose substantial obstacles to explore their functions. Here, by preparing a N-doped carbon-supported bifunctional cobalt catalyst (Co-DAPhen/C), it was applied to develop a reductive tandem reaction for general synthesis of AHBA derivatives from cheap and abundant nitroarenes, formaldehyde, and acrylates. This catalytic three-component reaction features broad substrate and functionality tolerance, easily accessible and reusable catalyst, and high step and atom economy. The active Co-sites of the catalyst are involved in the mild reduction processes with formic acid, whereas the N-doped carbon support enriches the HCHO and acrylates by physical adsorption, thus favoring the capture of hydroxylamine and nitrone intermediates via the condensation and 1,3-dipolar cycloaddition, respectively. Such a metal-support synergy interrupts the conventional reduction of nitroarenes into anilines, and results in a novel tandem reaction route. In this work, the concept merging mild reduction and effective intermediate transformations is anticipated to develop more useful tandem reactions by rational catalyst design.

J. Am. Chem. Soc., 2025, 147, Doi: org/10.1021/jacs.4c15284.

Article link: https://pubs.acs.org/doi/10.1021/jacs.4c15284