中国科学院大连化学物理研究所乔波涛团队近日研究了钯单原子催化剂催化苯基醇α。这一研究成果于2025年6月2日发表《德国应用化学》杂志上。

催化氢氘交换（HDE）已成为实现位点选择性氘化和生物活性分子精确标记的有价值的工具。通过这种方法，在代谢不稳定的位置掺入氘，可以通过动力学同位素效应潜在地提高药物疗效。然而，在特定分子位置实现氘的精确、位点选择性掺入仍然具有挑战性。

研究组报道了一种通过钯单原子催化剂（SAC）对苄醇进行高效α位选择性HDE的方法。通过使用Pd-SAC，在HDE反应中实现了异常的活性和选择性，在α-位置提供了高达95%的氘掺入（D-inc.），同时有效抑制了不期望的途径（例如，α、β-多位点氘代）。 

机理研究表明，Pd-SAC通过两种不同的表面途径促进位点选择性HDE：（i）以前未报道的直接C-H键活化和（ii）改进的借用氢过程，其中高压氢抑制酮烯醇互变异构，从而在很大程度上绕过α，β多位点氘化。该催化剂表现出强大的稳定性、可重复使用性和广泛的底物兼容性，突显了其实际应用的潜力。这项工作标志着用于位点选择性氘化的非均相单原子催化方法取得了重大进展，为催化有机合成中长期存在的挑战提供了补充解决方案。

附：英文原文

Title: Catalytic α-Site-Selective Hydrogen-Deuterium Exchange of Benzylic Alcohols by Palladium Single-Atom Catalyst

Author: Shu-Xian Li, Xiang-Ting Min, Juan Su, Boyu Yu, Wenhao Cui, Jing-Jing Tang, Botao Qiao

Issue&Volume: 2025-06-02

Abstract: Catalytic hydrogen-deuterium exchange (HDE) has emerged as a valuable tool for achieving site-selective deuteration and the precision labelling of bioactive molecules. Incorporation of deuterium at metabolically labile positions, enabled by such methods, can potentially improve drug efficacy through the kinetic isotope effect. However, achieving precise, site-selective incorporation of deuterium at specific molecular positions remains challenging. Herein, we report a highly efficient α-site-selective HDE of benzylic alcohols via a palladium single-atom catalyst (SAC). By using the Pd SAC, exceptional activity and selectivity in HDE reactions were achieved, delivering up to 95% deuterium incorporation (D-inc.) at the α-position while effectively suppressing undesired pathways (e.g., α,β-multisite deuteration). Mechanistic investigations reveal that the Pd SAC promotes site selective HDE through two distinct surface pathways: (i) a previously unreported direct C–H bond activation and (ii) a modified borrowing hydrogen process in which high-pressure hydrogen inhibits the keto enol tautomerization, thereby largely circumvents α,β-multisite deuteration. The catalyst exhibits robust stability, reusability, and broad substrate compatibility, underscoring its potential for practical applications. This work marks a significant advance in heterogeneous single-atom catalytic methodologies for site-selective deuteration, offering a complementary solution to longstanding challenges in catalytic organic synthesis.

DOI: 10.1002/anie.202507338

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202507338