154532-34-0Relevant articles and documents
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Newman,Easterbrook
, p. 3763,3764 (1955)
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Dual Ligand-Enabled Nondirected C-H Cyanation of Arenes
Chen, Hao,Mondal, Arup,Wedi, Philipp,Van Gemmeren, Manuel
, p. 1979 - 1984 (2019/02/19)
Aromatic nitriles are key structural units in organic chemistry and, therefore, highly attractive targets for C-H activation. Herein, the development of an arene-limited, nondirected C-H cyanation based on the use of two cooperatively acting commercially available ligands is reported. The reaction enables the cyanation of arenes by C-H activation in the absence of directing groups and is therefore complementary to established approaches.
Palladium-Catalyzed Late-Stage Direct Arene Cyanation
Zhao, Da,Xu, Peng,Ritter, Tobias
supporting information, p. 97 - 107 (2019/01/21)
Methods for direct benzonitrile synthesis are sparse, despite the versatility of cyano groups in organic synthesis and the importance of benzonitriles for the dye, agrochemical, and pharmaceutical industries. We report the first general late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance. The reaction is enabled by a dual-ligand combination of quinoxaline and an amino acid-derived ligand. The method is applicable to direct cyanation of several marketed small-molecule drugs, common pharmacophores, and organic dyes. Benzonitriles are some of the most versatile building blocks for organic synthesis, in particular in the pharmaceutical industry, but general methods to make them by direct C–H functionalization are unknown. In this issue of Chem, Ritter and coworkers describe a late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance, enabled by a palladium-dual-ligand catalyst system. The reaction may serve for the late-stage modification of drug candidates. Aryl nitriles constitute an important class of organic compounds that are widely found in natural products, pharmaceuticals, agricultural chemicals, dyes, and materials. Moreover, nitriles are versatile building blocks to access numerous other important molecular structure groups. However, no general method for direct aromatic C–H cyanation is known. All approaches to date require either an appropriate directing group or reactive electron-rich substrates, such as indoles, which limit their synthetic applications. Here we describe an undirected, palladium-catalyzed late-stage aryl C–H cyanation reaction for the synthesis of complex aryl nitriles that would otherwise be more challenging to produce. The wide substrate scope and good functional-group tolerance of this reaction provide direct and quick access to structural diversity for pharmaceutical and agrochemical development.
