美国罗格斯大学Szostak, Michal团队报道了炔与硝基芳烃还原性氢胺化反应合成金催化胺。相关研究成果于2024年9月25日发表在《自然—化学》。

胺是药物化合物中最关键的一类有机基序。

该文中，研究人员展示了一个通过三重Au-H/Au⁺/Au-H中继催化，实现的催化剂分化来合成胺的路线。母体催化剂被区分为一组催化活性物质，以实现三级级联催化，其中每种催化物质都针对一个催化循环进行了专门的调整。该策略能够通过炔烃与硝基芳烃的还原氢胺化来合成生物相关胺基序。

使用这种三级联方法，研究人员实现了卓越的官能团耐受性，使散装化学原料能够用作简单和复杂炔烃（>100个例子）胺化的偶联剂，包括来自药物、肽和天然产物的炔烃（>30个例子）。

金氢化物和氢化物桥联金配合物的分离和全晶体学表征，为基本有机金属金氢化物配合物的催化剂分化过程提供了见解。

附：英文原文

Title: Gold-catalysed amine synthesis by reductive hydroamination of alkynes with nitroarenes

Author: Zhou, Tongliang, Gao, Pengcheng, Lalancette, Roger, Szostak, Roman, Szostak, Michal

Issue&Volume: 2024-09-25

Abstract: Amines are the most pivotal class of organic motifs in pharmaceutical compounds. Here we provide a blueprint for a general synthesis of amines by catalyst differentiation enabled by triple Au–H/Au+/Au–H relay catalysis. The parent catalyst is differentiated into a set of catalytically active species to enable triple cascade catalysis, where each catalytic species is specifically tuned for one catalytic cycle. This strategy enables the synthesis of biorelevant amine motifs by reductive hydroamination of alkynes with nitroarenes. Using this triple cascade approach, we have achieved exceptional functional group tolerance, enabling the use of bulk chemical feedstocks as coupling partners for the amination of both simple and complex alkynes (>100 examples), including those derived from pharmaceuticals, peptides and natural products (>30 examples). The isolation and full crystallographic characterization of gold hydride and hydride-bridged gold complexes has garnered insights into the catalyst differentiation process of fundamental organometallic gold hydride complexes.

DOI: 10.1038/s41557-024-01624-8

Source: https://www.nature.com/articles/s41557-024-01624-8