Palladium-Catalyzed Synthesis of Diaryl Ketones from Aldehydes and (Hetero)Aryl Halides via C–H Bond Activation

Abstract

We developed a palladium-catalyzed C−H transformation that enabled the synthesis of ketones from aldehydes and (hetero)aryl halides. The use of picolinamide ligands was key to achieving the transformation. Heteroaryl ketones, as well as diaryl ketones, were synthesized in good to excellent yields, even in gram-scale, using this reaction. Results of density functional theory (DFT) calculations support the C−H bond activation pathway.

Benzophenone: a ubiquitous scaffold in medicinal chemistry

“…23 Very recently, Kuninobu and Kanai reported the synthesis of diaryl ketones from aldehydes and aryl halides using a palladium/picolinamide catalyst. 24 Various other catalysts have also been used with different coupling partners and aldehydes to afford various unsymmetrical diaryl ketones. [25][26][27][28][29][30] In this area, transition-metal-catalyzed oxidative C-H acylation and decarboxylative acylation of unactivated sp 2 arene C-H bonds using different acyl sources, such as aldehyde, benzyl alcohol, benzylamine, toluene, and α-keto acids, has been recently developed.…”

An efficient 3-acylquinoline synthesis from acetophenones and anthranilviaC(sp3)–H bond activation mediated by Selectfluor

“…3-Acylquinolines have been reported to possess herbicidal activity 46 as well as antihypertensive activity. 47 Some efficient methods for the preparation of 3-acylquinolines have been developed, such as Pd-catalyzed carbonylative Suzuki crosscoupling reactions of arylboronic acid with 3-iodoquinoline, 48 Pd-catalyzed coupling of aldehydes and 3-bromoquinoline 49 or arylboronic acid and 3-quinolinecarbaldehyde, 50 Fe-catalyzed cascade Michael addition/cyclization of o-aminoaryl aldehydes/ketones/alcohols with ynones, 45 and domino reactions between N,N-dimethyl enaminones and anilines. 41 In addition, dehydrogenation of saturated carbonyl compounds to afford a,b-unsaturated carbonyl derivatives has been found to be compatible with other organic transformations, leading to efficient one-pot protocols for the synthesis of functionalized molecules.…”

Palladium-Catalyzed Ligand-Free Decarboxylative Coupling of α- Oxocarboxylic Acid with Aryl Diazonium Tetrafluoroborate: An Access to Unsymmetrical Diaryl Ketones

“…However, the ligands are usually expensive and the reactions are performed at elevated temperature. 13 Hence, a more simple and efficient procedure for the synthesis of diaryl ketones is still desired. Earlier methods based on decarboxylative coupling were reported using costly ligands (Scheme 1).…”