Merchant Rohan R, Edwards Jacob T, Qin Tian, Kruszyk Monika M, Bi Cheng, Che Guanda, Bao Deng-Hui, Qiao Wenhua, Sun Lijie, Collins Michael R, Fadeyi Olugbeminiyi O, Gallego Gary M, Mousseau James J, Nuhant Philippe, Baran Phil S
Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Asymchem Life Science (Tianjin), Tianjin Economic-Technological Development Zone, Tianjin 300457, China.
Science. 2018 Apr 6;360(6384):75-80. doi: 10.1126/science.aar7335. Epub 2018 Feb 18.
Cross-coupling chemistry is widely applied to carbon-carbon bond formation in the synthesis of medicines, agrochemicals, and other functional materials. Recently, single-electron-induced variants of this reaction class have proven particularly useful in the formation of C(sp)-C(sp) linkages, although certain compound classes have remained a challenge. Here, we report the use of sulfones to activate the alkyl coupling partner in nickel-catalyzed radical cross-coupling with aryl zinc reagents. This method's tolerance of fluoroalkyl substituents proved particularly advantageous for the streamlined preparation of pharmaceutically oriented fluorinated scaffolds that previously required multiple steps, toxic reagents, and nonmodular retrosynthetic blueprints. Five specific sulfone reagents facilitate the rapid assembly of a vast set of compounds, many of which contain challenging fluorination patterns.
交叉偶联化学在药物、农用化学品和其他功能材料的合成中广泛应用于碳-碳键的形成。最近，这类反应的单电子诱导变体已被证明在形成C(sp)-C(sp)键方面特别有用，尽管某些化合物类别仍然具有挑战性。在此，我们报道了使用砜来活化烷基偶联配偶体，用于与芳基锌试剂进行镍催化的自由基交叉偶联。该方法对氟烷基取代基的耐受性被证明对于简化制备以前需要多步、有毒试剂和非模块化逆合成蓝图的面向药物的氟化支架特别有利。五种特定的砜试剂有助于快速组装大量化合物，其中许多含有具有挑战性的氟化模式。
