Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds.
Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds.
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DOI：
10.3762/bjoc.7.10
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发表时间：
2011-01-14
影响因子：
2.7
通讯作者：
Koenig B
中科院分区：
文献类型：
--
作者：
Fischer C;Koenig B
n -芳基化脂肪胺和芳香胺是许多生物活性化合物的重要取代基。在过去的几年里，过渡金属介导的n-芳基键的形成已经成为一种标准的程序引入胺到芳香体系。虽然简单胺对简单芳香族卤化物的n -芳基化在许多描述的方法中都能高产出，但如果应用于具有附加官能团的复杂分子的合成，例如天然产物或药物，则可能需要详细的优化反应。本文讨论并比较了钯催化的buchwald - hartwigh型反应、铜介导的ullmann型反应和chan - lam型n-芳基化反应这三种主要的n-芳基化方法在生物活性化合物合成中的应用。所讨论的例子表明，钯催化反应有利于大规模应用，并且比Chan-Lam反应更能容忍偶联体上的立体要求取代基。Chan-Lam n -芳基化特别温和，不需要额外的配体，这有利于工作。然而，反应时间可能很长。Ullmann-和buchwald - hartwig型方法已被用于分子内反应，从而获得复杂的环结构。所有三种n -芳基化方法都有其特定的优点和缺点，在全合成或药物合成过程中选择所需的C-N键形成的反应条件时应考虑这些优点和缺点。
N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald–Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis.
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影响因子：
3.4
作者：
Federsel, Hans-Juergen;Hedberg, Martin;Tian, Wei
通讯作者：
Tian, Wei
影响因子：
15
作者：
Barluenga, Jose;Jimenez-Aquino, Agustin;Valdes, Carlos
通讯作者：
Valdes, Carlos
影响因子：
3.6
作者：
Collman, JP;Zhong, M;Costanzo, S
通讯作者：
Costanzo, S
影响因子：
7.3
作者：
Aguado, Leire;Thibaut, Hendrik Jan;Perez-Perez, Maria-Jesus
通讯作者：
Perez-Perez, Maria-Jesus
影响因子：
2.1
作者：
Browning, RG;Badarinarayana, V;Lovely, CJ
通讯作者：
Lovely, CJ