Mild Palladium‐Catalyzed Oxidative Direct ortho‐CH Acylation of Anilides under Aqueous Conditions

Abstract

Palladium-catalyzed cross-dehydrogenative coupling between anilides and aromatic aldehydes was achieved under aqueous conditions. A wide variety of the desired benzophenone derivatives was isolated in good to excellent yield. The reaction rate acceleration effect of acid and detergent has been demonstrated. Mechanistic insight has been obtained from quantum chemical calculations.Transition metal-catalyzed direct C À H bond functionalization is one of the most important transformations in recent organic synthetic strategies. [1] Although catalytic transformations based on palladium catalysts are the most frequently utilized oxidative coupling methods in organic syntheses, these reactions usually require harsh conditions (high temperature, long reaction time, necessity of inert atmosphere). Therefore the development of efficient palladium-catalyzed oxidative couplings based on highly active catalyst systems under mild reaction conditions is still highly demanded. Regarding the mechanisms of palladium-catalyzed transformations the presence of monometallic palladium complexes in the catalytic cycle is well accepted. [2] However, very recently the special role and activity of bimetallic palladium species has been discovered and demonstrated in several coupling reactions involving a C À H functionalization step. [3] Be-sides the assessment of the synthetic potential of bimetallic complexes in organic chemistry, a thorough understanding of their working mechanism is also essential. [4] There are several applications of palladium-catalyzed oxidative transformations for the formation of new carbon-carbon bonds via functional group-directed ortho-substitution. [5] Very recently, the synthesis of aromatic ketones from phenylpyridines [6] or acetanilides [7] could be achieved by the palladium-catalyzed oxidative coupling of aldehydes [8] including a C À H activation step.The recently described methodologies of Zhou, [7a] Kwong [7b] and Yu [7c] enable the transformation in toluene at 120 8C, 90 8C, and 40 8C, respectively (Scheme 1.). The latter procedure provides the most efficient conditions for the desired coupling due to the relatively short reaction time under the applied conditions (40 8C, 3 h). Utilization of ketocarboxylic acids instead of aldehydes enables the formation of benzophenone derivatives in a similar palladium-catalyzed coupling at room temperature as it was demonstrated by Ge and co-workers. [9] This transformation works efficiently at room temperature and it has excellent functional group tolerance.It is of note, amongst the previous methodologies depicted on Scheme 1., that only Kwongs proce-A C H T U N G T R E N N U N G dure [7b] offers possibilities for the transformation of ortho-substituted acetanilides.Palladium-catalyzed oxidative coupling of acetanilides with aromatic aldehydes results in 2-acylacetanilides and 2-aminobenzophenone derivatives after hydrolytic cleavage of the amide bond, which are impor-

Palladium-catalysed directed C–H activation by anilides and ureas; water participation in a general base mechanism

“…19 The computed reaction stage shown in Scheme 3 proceeded with an activation free energy barrier of 17.1 kcal mol −1 . With butyl acrylate as co-reactant palladacycle formation is turnoverlimiting, and the rate is accelerated by added p-TsOH.…”

Silver‐Catalyzed Chemo‐ and Regioselective Nitration of Anilides

“…Other reagents were purchased from commercial distributors and were used without further purification. Anilide and aromatic sulfonamide were synthesized according to the literature. Analytical thinlayer chromatography (TLC) was performed on precoated silica gel60 F254 plates.…”

Palladium nanoparticles supported on organofunctionalized kaolin as an efficient heterogeneous catalyst for directed C–H functionalization of arylpyrazoles

“…[1][2][3][4][5][6][7][8][9][10][11] In this context, pyrazole serves as an effective directing group for C-H functionalization methods involving cyclometalation. But, at present, methods for directed C-H acylation of 1-arylpyrazole 12 are relatively scarce while there are numerous reports on directed C-H acylation of 2-phenyl pyridine (see Scheme 1).…”