C-H Alkylation of Aldehydes by Merging TBADT Hydrogen Atom Transfer with Nickel Catalysis
C-H Alkylation of Aldehydes by Merging TBADT Hydrogen Atom Transfer with Nickel Catalysis
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DOI：
10.1021/acs.orglett.1c01716
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发表时间：
2021-06-25
期刊：
影响因子：
5.2
通讯作者：
Rasappan, Ramesh
中科院分区：
文献类型：
--
作者：
Murugesan, Vetrivelan;Ganguly, Anirban;Rasappan, Ramesh
催化剂控制的位置选择性C-H官能化是有机合成中具有挑战性但强有力的工具。极性匹配和空间控制的氢原子转移（HAT）为位点选择性官能化提供了极好的机会。因此，双Ni/光氧化还原系统被成功地用于通过选择性甲酰基C-H活化从醛产生酰基自由基，随后交叉偶联以产生酮，酮是存在于绝大多数天然和生物活性分子中的普遍存在的结构基序。然而，只有少数的例子，限制使用芳基卤化物的开发。鉴于胺的广泛可用性，我们首次开发了使用经济的镍和TBADT催化剂通过C-N键断裂的交叉偶联反应。一系列烷基和芳基醛与苄基和烯丙基吡啶盐交叉偶联，得到具有广谱官能团耐受性的酮。即使在α-亚甲基羰基或α-氨基/氧亚甲基存在下，也获得了对甲酰基C-H键的高区域选择性。
Catalyst controlled site-selective C-H functionalization is a challenging but powerful tool in organic synthesis. Polarity-matched and sterically controlled hydrogen atom transfer (HAT) provides an excellent opportunity for site-selective functionalization. As such, the dual Ni/photoredox system was successfully employed to generate acyl radicals from aldehydes via selective formyl C-H activation and subsequently cross-coupled to generate ketones, a ubiquitous structural motif present in the vast majority of natural and bioactive molecules. However, only a handful of examples that are constrained to the use of aryl halides are developed. Given the wide availability of amines, we developed a cross-coupling reaction via C-N bond cleavage using the economic nickel and TBADT catalyst for the first time. A range of alkyl and aryl aldehydes were cross-coupled with benzylic and allylic pyridinium salts to afford ketones with a broad spectrum of functional group tolerance. High regioselectivity toward formyl C-H bonds even in the presence of alpha-methylene carbonyl or aamino/oxy methylene was obtained.