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C3-Cyanation of Pyridines: Constraints on Electrophiles and Determinants of Regioselectivity |
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| Authors: | Ming Zhang Qingyang Zhou Heng Luo Zi-Lu Tang Prof Dr Xiufang Xu Prof Dr Xiao-Chen Wang |
| Institution: | 1. State Key Laboratory and Institute of Elemento-Organic Chemistry, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, 94 Weijin Road, Tianjin, 300071 China;2. Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), College of Chemistry, Nankai University, 94 Weijin Road, Tianjin, 300071 China |
| Abstract: | Methods for C−H cyanation of pyridines are rare. Here, we report a method for C3-selective cyanation of pyridines by a tandem process with the reaction of an in situ generated dihydropyridine with a cyano electrophile as the key step. The method is suitable for late-stage functionalization of pyridine drugs. The low reduction potential of the electrophile and effective transfer of the nitrile group were found to be essential for the success of this method. We studied the reaction mechanism in detail by means of control experiments and theoretical calculations and found that a combination of electronic and steric factors determined the regioselectivity of reactions involving C2-substituted pyridines. |
| Keywords: | Boron C−H Functionalization Cyanation Heterocycles Pyridine |