双镍/光氧化还原催化的位阻伯胺的脱氨基交叉偶联反应。
Dual Nickel/Photoredox-Catalyzed Deaminative Cross-Coupling of Sterically Hindered Primary Amines.
机构信息
Department of Chemistry, Columbia University, New York, New York 10027, United States.
出版信息
J Am Chem Soc. 2021 Nov 24;143(46):19294-19299. doi: 10.1021/jacs.1c10150. Epub 2021 Nov 12.
Abstract
We report a method to activate α-3° amines for deaminative arylation via condensation with an electron-rich aldehyde and merge this reactivity with nickel metallaphotoredox to generate benzylic quaternary centers, a common motif in pharmaceuticals and natural products. The reaction is accelerated by added ammonium salts. Evidence is provided in support of two roles for the additive: inhibition of nickel black formation and acceleration of the overall reaction rate. We demonstrate a robust scope of amine and haloarene coupling partners and show an expedited synthesis of ALK2 inhibitors.
摘要
我们报告了一种通过与富电子醛缩合激活α-3°胺以进行脱氨芳基化的方法，并将这种反应性与镍金属光氧化还原合并，以生成苄基季铵中心，这是药物和天然产物中的常见结构基序。反应通过添加铵盐加速。有证据表明添加剂具有两种作用：抑制镍黑的形成和加速整体反应速率。我们展示了胺和卤代芳烃偶联伙伴的强大范围，并展示了ALK2 抑制剂的快速合成。
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