铱（III）催化吡啶离子加氢制多取代哌啶，这一成果由瑞士洛桑联邦理工学院Nicolai Cramer小组经过不懈努力而取得。该项研究成果发表在2025年12月2日出版的《自然—化学》上。

在这里小组描述了一个方法和选择性的铱（III）催化的离子加氢吡啶到相应的功能化哌啶。重要的高度还原敏感基团，包括硝基、叠氮基、溴基、烯基和炔基，都是惰性的，因此可以高产地获得广泛的多取代哌啶，大大扩大了这种相关支架的可用化学空间。该方法需要低催化剂负载，可扩展到10克，并提供最有合成价值的游离仲胺作为易于分离和稳定的胡椒鎓盐。应用于复杂的后期设置，吡啶基序在几个FDA批准的药物成功和选择性氢化。

研究人员表示，哌啶和吡啶是氮杂环基序，在制药领域具有重要意义。平面吡啶直接还原成高sp³碳含量的哌啶具有很高的吸引力，这为生产高价值产品和拓宽结构空间提供了途径。然而，由于均相催化剂的芳香稳定性和催化中毒能力，用均相催化剂直接加氢吡啶具有挑战性。

附：英文原文

Title: Iridium(III)-catalysed ionic hydrogenation of pyridines to multisubstituted piperidines

Author: Despois, Arthur, Cramer, Nicolai

Issue&Volume: 2025-12-02

Abstract: Piperidine and pyridine are nitrogen heterocyclic motifs prominently used in pharmaceuticals and consequently of great importance. The direct reduction of planar pyridines into piperidines with high sp3-carbon content is highly attractive as this offers a route to producing high-value products and broadening the structural space. However, direct hydrogenation of pyridines with homogeneous catalysts is challenging due to their aromatic stability and catalyst-poisoning abilities. Here we describe a robust and selective iridium(III)-catalysed ionic hydrogenation of pyridines to corresponding functionalized piperidines. Important highly reduction-sensitive groups, including nitro, azido, bromo, alkenyl and alkynyl, are inert, enabling access to a broad range of multisubstituted piperidines in high yields, substantially expanding the available chemical space for this relevant scaffold. The method requires low catalyst loadings, is scalable to decagrams and delivers the most synthetically valuable free secondary amines as easily isolable and stable piperidinium salts. Applied in a complex late-stage setting, the pyridine motif in several FDA-approved drugs was successfully and selectively hydrogenated.

DOI: 10.1038/s41557-025-02008-2

Source: https://www.nature.com/articles/s41557-025-02008-2