Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, China.
J Org Chem. 2012 Jan 6;77(1):501-10. doi: 10.1021/jo202087j. Epub 2011 Dec 20.
A silver-mediated tandem protocol for the synthesis of quinolines involving the oxidative coupling/cyclization of N-arylimines and alkynes has been developed. We demonstrated that scenario-dependent metalation could occur either at the ortho C-H bond of an N-arylimine through protonation-driven enhancement of acidity or at the terminal C-H bond of an alkyne by virtue of the carbophilic π-acidity of silver. The diverse set of mechanistic manifolds implemented with a single type of experimental protocol points toward the importance of stringent reactivity analysis of each individual potentially reactive molecular site. Importantly, the direct arene C-H bond activation provides a unique and distinct mechanistic handle for the expansion of reactivity paradigms for silver. As expected, the protocol allows for the incorporation of both internal and terminal alkynes into the products, and in addition, both electron-withdrawing and -donating groups are tolerated on N-arylimines, thus enabling the vast expansion of substituent architectures on quinoline framework. Further, an intriguing phenomenon of structural isomerization and chemical bond cleavage has been observed for aliphatic internal alkynes.
一种银介导的串联反应协议被开发出来，用于合成喹啉，涉及 N-芳基亚胺和炔烃的氧化偶联/环化。我们证明，通过质子化增强酸度，可以在 N-芳基亚胺的邻位 C-H 键上发生情景依赖的金属化，或者通过银的亲电性 π-酸度，在炔烃的末端 C-H 键上发生金属化。用单一类型的实验方案实现的各种机理流形表明，严格分析每个潜在反应性分子位点的反应性非常重要。重要的是，直接芳基 C-H 键活化为银的反应性范式的扩展提供了一个独特而不同的机理控制。正如预期的那样，该方案允许内部和末端炔烃都掺入产物中，此外，N-芳基亚胺上也可以容忍吸电子和给电子基团，从而能够极大地扩展喹啉骨架上的取代基结构。此外，对于脂肪族内部炔烃，观察到了结构异构化和化学键断裂的有趣现象。
