Recently, our team, led by Researcher Botao Qiao, Assistant Researcher Xiangting Min, and Dr. Jingjing Tang from Dalian University of Technology, has made new progress in the site-selective deuteration of benzyl alcohol compounds using palladium single-atom catalysts. The research team utilized the synthesized Pd1/FeOx single-atom catalyst (Pd SAC) to achieve efficient α-site selective hydrogen-deuterium exchange (HDE) of benzyl alcohol compounds under mild conditions, providing a new method for the synthesis of deuterated benzyl alcohol compounds.
Benzyl alcohol compounds are important structural units in drug development. The α-position C(sp3)-H bond, as a metabolic "soft spot," can be selectively deuterated to optimize metabolism, extend the half-life, and reduce side reactions, making it a key strategy for drug optimization. However, existing methods are limited by reliance on expensive deuteration reagents, harsh conditions, and poor site selectivity. In recent years, single-atom catalysts (SACs) have gained significant attention due to their unique structure and high activity, particularly in C(sp3)-H bond activation. Therefore, SACs hold promise for achieving site-selective deuteration of benzyl alcohol at the α-position through direct C-H bond activation, avoiding the traditional hydrogen borrowing process, and offering a new direction for the development of drug deuteration technologies.
Based on the team's long-term experience in single-atom catalysis, this study developed a palladium single-atom catalyst (Pd SAC). The catalyst achieves efficient site-selective deuteration of benzyl alcohol through direct C-H bond activation (avoiding β-position deuteration) and a non-eneal hydrogen borrowing process. Additionally, the α/β deuteration ratio can be controlled by adjusting hydrogen pressure. Experimental results show that Pd SAC not only exhibits excellent stability but also has broad substrate tolerance, enabling high selectivity for α-position deuteration in 29 structurally diverse benzyl alcohol derivatives.
Xiangting Min, Botao Qiao, and others have made a series of advancements in deuteration reaction research (J. Am. Chem. Soc., 2022) and in the research of homogeneous catalysis for heterogeneous catalysis in single-atom catalysis (Angew. Chem. Int. Ed., 2016; Angew. Chem. Int. Ed., 2020; Angew. Chem. Int. Ed., 2020).
The aforementioned achievements were published in Angewandte Chemie International Edition under the title "Catalytic α-Site-Selective Hydrogen-Deuterium Exchange of Benzylic Alcohols by Palladium Single-Atom Catalyst." The co-first authors of this work are Shuxian Li, a master's student jointly trained by Dalian University of Technology and our institute, and Xiangting Min from Group 1502. This work was supported by the National Key Research and Development Program, the National Natural Science Foundation, the "Single-Atom Catalysis" Basic Science Center Project of the National Natural Science Foundation, and the Liaoning Provincial Natural Science Foundation, among others.
Paper Link:https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202507338
