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.

Synthesis of Quinoline Derivatives by Multicomponent Reaction Using Niobium Pentachloride as Lewis Acid

“…In Table can be noted, that independent of the Lewis acid used , the presence of solvent and high temperatures are necessary to obtain good yields on synthesis of quinoline derivatives. The NbCl 5 when compared with other Lewis acids is efficient and present similar results, with good reaction times and competitive yields.…”

“…Because of the applicability of several Lewis acids in this type of reaction , in this work we have reported our studies on the use of niobium pentachloride (NbCl 5 ) as a catalyst in these multicomponent reactions. The NbCl 5 forms chloro‐bridged dimers in its solid state, in which each metal is surrounded by a distorted octahedron of chlorine atoms.…”

Silver‐Catalyzed Oxidative Coupling of Aniline and Ene Carbonyl/Acetylenic Carbonyl Compounds: An Efficient Route for the Synthesis of Quinolines

“…[11] The Pd-catalyzed approach to quinolines from 2-iodoanilines was also described by Cho and Kim. [13] The cross-coupling reactions can lead to an improved overall efficiency of the desired transformation. [13] The cross-coupling reactions can lead to an improved overall efficiency of the desired transformation.…”

A Novel Efficient Route for Acid-Catalyzed Synthesis of α,β-Alkynyl/Alkenyl Ketones

“…Firstly, the initial addition of Ag + activated terminal alkynes to iminium ions and a subsequent addition by the attack of the double bond to the protonated imine, 16 which was followed by deprotonation, oxidatation, and hydrolysis to yield the final product. The mechanism for the synthesis of α,β-alkenyl ketones may be similar to HOTf-catalyzed three-component reactions of aldehydes, amines, and alkynes: 17 alkyne attack of the double bond to the protonated imine is followed by deprotonation and hydrolysis to yield the final product.…”