Department of Chemistry , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 , United States.
Center for Synthetic Organic Electrochemistry , 315 South 1400 East , Salt Lake City , Utah 84112 , United States.
J Am Chem Soc. 2019 Apr 17;141(15):6392-6402. doi: 10.1021/jacs.9b01886. Epub 2019 Apr 2.
C-N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments, the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles including complex examples on oligopeptides, medicinally relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations and procedures for both batch and flow scale-ups (100 g) are also described.
C-N 交叉偶联是有机合成中最有价值和最广泛的转化之一。它主要由 Pd 和 Cu 基催化体系主导，已被证明是学术界和工业界的一项重要转化。本研究提出了一种电化学驱动的、Ni 催化的方法来实现这一具有高战略重要性的反应，并对其发展和机理理解进行了阐述。通过一系列电化学、计算、动力学和经验实验，揭示了该反应的关键机理特征，从而得到了第二代条件，适用于广泛的芳基卤化物和胺亲核试剂，包括寡肽、药用杂环、天然产物和糖等复杂实例。还全面介绍了分批和流量放大（100 克）的当前限制和程序。
