Palladium-Catalyzed Directed Aldehyde C–H Arylation of Quinoline-8-carbaldehydes: Exploring the Reactivity Differences between Aryl (Pseudo) Halides

Abstract

We have developed a method for Pd-catalyzed direct C–H arylation of quinoline-8-carbaldehydes with either aryl iodides or aryl diazonium salts for the synthesis of aryl quinolinyl ketones. Aryl iodide substituted with an electron-donating group favors the reaction, whereas aryl diazonium salt substituted with an electron-withdrawing group showed excellent reactivity. A range of aryl quinolinyl ketones were synthesized in good-to-excellent yields, with very good functional group tolerance. Our methodology was successfully applied to synthesize highly potent tubulin polymerization inhibitors and can be easily scaled up to a gram scale.

Palladium-Catalyzed Chelation-Assisted Aldehyde C–H Bond Activation of Quinoline-8-carbaldehydes: Synthesis of Amides from Aldehydes with Anilines and Other Amines

“…From the mass spectroscopy of the crude reaction mixture, a dimeric organometallic Pd metallacycle was identified (Scheme 2D; for more details, see the Supporting Information Scheme S1), which indicates the activation of the aldehyde C−H bond by palladium, as observed earlier. 19 To gain more insights into the reaction mechanism, next, Hammett's studies were executed by varying the electronic effect of a series of para-and metasubstituted anilines and analyzing the influence of their effect on their initial reaction rate (Figure 1). The plot of the logarithm of the relative rate constants against Hammett constants indicates a good correlation, as shown in Figure 1; a Hammet ρ value of (−) 0.7267 was obtained, indicating that the presence of the electron-donating group of aryl amine favors the reaction.…”

“…In all of these cases, expensive Rh catalysts and masked or activated aminating agents were used. In continuation of our work on C–H bond activation, we have recently reported Pd-catalyzed directed C–H arylation of quinoline-8-carbaldehydes with aryl (pseudo) halides . Encouraged by this result, we approached the directed aldehyde C–H amination to build up an important amide linkage.…”

“…In continuation of our work on C−H bond activation, 18 we have recently reported Pd-catalyzed directed C−H arylation of quinoline-8-carbaldehydes with aryl (pseudo) halides. 19 Encouraged by this result, we approached the directed aldehyde C−H amination to build up an important amide linkage. We herein report Pd-catalyzed aldehyde C−H amination with simple anilines and aliphatic amines to afford a variety of N-aryl/alkyl-quinoline-8-carboxamide.…”

Cobalt‐Catalyzed, 2‐Aminopyridine‐N‐Oxide‐Directed C(sp2)−H Bond Functionalization with Maleimides: Facile Access to Isoindolone Spirosuccinimides

“…[11] We anticipated that 2-aminopyridine-1-oxide (PNO) as an N, O-bidentate directing group attached with benzamides can perform a similar kind of reaction under milder conditions based on the following factors a) the N and O atoms might provide ideal bidentate chelating centers for Co salt to form a stable 5-membered metallacycle; b) since the reaction likely proceeds through a high-valent cobalt complex, an anionic auxiliary would help in stabilizing high-energy cobalt (III) complexes and c) it could be easier for cobalt salts to activate C(sp 2 )À H bonds. As part of our ongoing interest in the field, [12] herein we report N, O bidentate directing group assisted cobalt-catalyzed spiroannulation of aryl amides with maleimides for facile access of isoindolone spirosuccinimides.…”

“…Additionally, the structure of compound 3 h was unambiguously confirmed by X-ray crystallography. [12] Next, we tested the reaction with unsymmetrical benzamides i. e., meta-substituted substrates. To our delight the reaction proceeded selectively on the less hindered side; the steric factor plays the role of selectivity.…”