Four‐Selective Pyridine Alkylation via Wittig Olefination of Dearomatized Pyridylphosphonium Ylides
Four‐Selective Pyridine Alkylation via Wittig Olefination of Dearomatized Pyridylphosphonium Ylides
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通过脱芳构化吡啶基鏻叶立德的 Wittig 烯化进行四选择性吡啶烷基化
DOI：
10.1002/anie.202109271
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
McNally, Andrew
中科院分区：
文献类型：
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作者：
Fricke, Patrick J.;Dolewski, Ryan D.;McNally, Andrew
合成烷基化吡啶的方法是有价值的，因为这些结构在药物和农用化学品中是普遍的。我们已经开发了一种独特的方法来构建4-烷基吡啶使用脱芳构化的吡啶基磷叶立德中间体在Wittig烯烃化rearomatization序列。吡啶的N-活化是这一策略的关键，N-三嗪基吡啶盐使各种取代的吡啶和醛之间的偶联成为可能。烷基化方案对于后期功能化是可行的，包括含吡啶药物的甲基化。这种方法代表了金属催化的sp2-sp3交叉偶联反应和Minisci型过程的替代方案。
Methods to synthesize alkylated pyridines are valuable because these structures are prevalent in pharmaceuticals and agrochemicals. We have developed a distinct approach to construct 4‐alkylpyridines using dearomatized pyridylphosphonium ylide intermediates in a Wittig olefination‐rearomatization sequence. PyridineN‐activation is key to this strategy, andN‐triazinylpyridinium salts enable coupling between a wide variety of substituted pyridines and aldehydes. The alkylation protocol is viable for late‐stage functionalization, including methylation of pyridine‐containing drugs. This approach represents an alternative to metal‐catalyzedsp2‐sp3cross‐coupling reactions and Minisci‐type processes.