Silver-Mediated C–H Activation: Oxidative Coupling/Cyclization of N-Arylimines and Alkynes for the Synthesis of Quinolines

Abstract

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.