Scholarlink

<p>Direct and selective functionalization of ubiquitous pyridine scaffold is of paramount importance across numerous fields, yet remains challenging due to the inherent inertness of pyridines and the presence of competing reactive sites. Here, using an undivided cell equipped with a zinc cathode, a graphite anode, and a TEMPO mediator, we report a room-temperature electrochemical strategy that enables the direct hydroxyalkylation of diverse pyridines with readily available carbonyl compounds. This method features a broad substrate scope, operational simplicity, metal-free conditions, and high step/atom economy. It overcomes the limitations of conventional approaches requiring pre-functionalized substrates or stoichiometric activators, establishing a practical platform for direct access to C4- or C2-hydroxyalkyl pyridines, depending on the substitution pattern of the pyridine substrates. Mechanistic studies reveal that acetic acid activates both reactants, and the products are formed via cross-coupling of cathodic reduction-induced pyridyl radicals and hydroxy <i>α</i>-radicals followed by protonation and anodic oxidative aromatization.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Room-temperature electrochemical hydroxyalkylation of pyridines

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月13日

查看全文
  • Chengqian Zhang,
  • Maorui Wang,
  • Pierre. H. Dixneuf,
  • Min Zhang

摘要

Direct and selective functionalization of ubiquitous pyridine scaffold is of paramount importance across numerous fields, yet remains challenging due to the inherent inertness of pyridines and the presence of competing reactive sites. Here, using an undivided cell equipped with a zinc cathode, a graphite anode, and a TEMPO mediator, we report a room-temperature electrochemical strategy that enables the direct hydroxyalkylation of diverse pyridines with readily available carbonyl compounds. This method features a broad substrate scope, operational simplicity, metal-free conditions, and high step/atom economy. It overcomes the limitations of conventional approaches requiring pre-functionalized substrates or stoichiometric activators, establishing a practical platform for direct access to C4- or C2-hydroxyalkyl pyridines, depending on the substitution pattern of the pyridine substrates. Mechanistic studies reveal that acetic acid activates both reactants, and the products are formed via cross-coupling of cathodic reduction-induced pyridyl radicals and hydroxy α-radicals followed by protonation and anodic oxidative aromatization.