Cu-Catalyzed C-N Coupling with Sterically Hindered Partners.
Cu-Catalyzed C-N Coupling with Sterically Hindered Partners.
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DOI：
10.1021/acscatal.0c02965
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发表时间：
2020-09
期刊：
影响因子：
12.9
通讯作者：
A. Modak;Alex J. Nett;E. Swift;Michael C. Haibach;V. Chan;T. S. Franczyk;S. Shekhar;S. Cook
中科院分区：
文献类型：
--
作者：
A. Modak;Alex J. Nett;E. Swift;Michael C. Haibach;V. Chan;T. S. Franczyk;S. Shekhar;S. Cook
铜是一种富含地球的金属，已重新成为Pd催化的多种碳-氮偶联的可行替代品。然而，连接空间受阻的反应伙伴仍然具有挑战性。在这里，我们公开了一种吡咯醇配体的发现和发展，以促进邻位取代的芳基碘化物与空间受阻的胺的偶联。该配体是通过文库筛选方法发现的，并突出了挖掘富含杂原子的药物文库以获得有用的配体基序的价值。进一步的评估表明，该配体在这些具有挑战性的转化中是唯一有效的。该反应使空间受阻的伯胺和仲胺、苯胺和酰胺能够偶联，具有广泛的官能团耐受性。
Copper, an earth-abundant metal, has reemerged as a viable alternative to the versatile Pd-catalyzed C-N coupling. Coupling sterically hindered reaction partners, however, remains challenging. Herein, we disclose the discovery and development of a pyrrole-ol ligand to facilitate the coupling of ortho-substituted aryl iodides with sterically hindered amines. The ligand was discovered through a library screening approach and highlights the value of mining heteroatom-rich pharmaceutical libraries for useful ligand motifs. Further evaluation revealed that this ligand is uniquely effective in these challenging transformations. The reaction enables the coupling of sterically hindered primary and secondary amines, anilines, and amides with broad functional group tolerance.