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吡啶C-H官能团化的进展:超越C2选择性

Advances in Pyridine C-H Functionalizations: Beyond C2 Selectivity.

作者信息

Mohite Sachin Balaso, Mirza Yafia Kousin, Bera Partha Sarathi, Nadigar Siddaram, Yugendhar Soorni, Karpoormath Rajsekhar, Bera Milan

机构信息

Department: Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa.

Department: Photocatalysis & Synthetic Methodology Lab (PSML), Amity Institute of Click Chemistry Research & Studies (AICCRS), Amity University, Noida, 201303, India.

出版信息

Chemistry. 2025 Jan 9;31(2):e202403032. doi: 10.1002/chem.202403032. Epub 2024 Dec 10.

Abstract

The pyridine core is a crucial component in numerous FDA-approved drugs and Environmental Protection Agency (EPA) regulated agrochemicals. It also plays a significant role in ligands for transition metals, alkaloids, catalysts, and various organic materials with diverse properties, making it one of the most important structural frameworks. However, despite its significance, direct and selective functionalization of pyridine is still relatively underdeveloped due to its electron-deficient nature and the strong coordinating ability of nitrogen. Among the variety of synthetic transformation, direct functionalization of C-H bond is straightforward and atom economical approach and it's advantageous for late-stage functionalization of pyridine containing drugs. In recent years, innovative strategies for regioselective C-H functionalization of pyridines and azines have emerged, offering numerous benefits such as high regioselectivity, mild conditions, and enabling transformations that were challenging with traditional methods. This review emphasizes the latest advancements in meta and para-C-H functionalization of pyridines through various approaches, including pyridine phosphonium salts, photocatalytic methods, temporary de-aromatization, Minisci-type reactions, and transition metal-catalyzed C-H activation techniques. We discuss the advantages and limitations of these current methods and aim to inspire further progress in this significant field.

摘要

吡啶核心是众多美国食品药品监督管理局(FDA)批准的药物和美国环境保护局(EPA)监管的农用化学品中的关键成分。它在过渡金属配体、生物碱、催化剂以及具有各种不同性质的有机材料中也起着重要作用,使其成为最重要的结构框架之一。然而,尽管其具有重要性,但由于吡啶的缺电子性质和氮的强配位能力,吡啶的直接和选择性官能团化仍然相对不发达。在各种合成转化中,C-H键的直接官能团化是一种直接且原子经济的方法,并且有利于含吡啶药物的后期官能团化。近年来,出现了用于吡啶和嗪的区域选择性C-H官能团化的创新策略,具有许多优点,如高区域选择性、温和的条件以及能够实现传统方法难以实现的转化。本综述强调了通过各种方法对吡啶进行间位和对位C-H官能团化的最新进展,包括吡啶鏻盐、光催化方法、暂时去芳构化、米尼西型反应以及过渡金属催化的C-H活化技术。我们讨论了这些现有方法的优点和局限性,旨在激发这一重要领域的进一步发展。

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