Palladium-Catalyzed Ortho C–H Arylation of Aniline Carbamates with Diazonium Salts under Mild Conditions: Expedient Synthesis of Carbazole Alkaloids

Abstract

Despite the significant progress, C–H arylation with aryldiazonium salts is a major challenge because of the faster rate of oxidative addition compared to the C–H insertion, leading to a deleterious homocoupling product. Recently, this limitation has been overcome by merging a photoredox catalyst with transition-metal catalysts which proceeds through a distinct single electron-transfer mechanism. However, we have observed that the photoredox catalyst is not necessary for the C–H arylation of aniline rather chemical reactivity can be controlled by tuning the electronic nature of the substrate. We report, herein, a palladium-catalyzed C–H arylation of aniline carbamates with aryldiazonium salts under external oxidant, acid, base free conditions at room temperature. Mechanistic studies suggest that the present reaction proceeds through a directed electrophilic metalation pathway which is the slowest step. However, the oxidative addition may take place through either ionic (2e – ) or radical (1e – ) pathway to generate hypervalent Pd(IV) or Pd(III) intermediate, respectively. A facile reductive elimination from the hypervalent palladium complex furnishes the C–H arylation product under mild conditions. The carbamate directing group is easily removed from the product to obtain the corresponding ortho-arylated aniline, which is a precursor for plethora of carbazole alkaloids and other biologically active molecules. The reaction is scaled-up to gram scale to furnish the desired product in comparable yields. Finally, we have applied this C–H arylation methodology for the synthesis of series of carbazole alkaloids such as clausine V, clauszoline K, O -methoxymahanine, and O -methylmurrayamine-D.

Iterative Arylation of Itaconimides with Diazonium Salts through Electrophilic Palladium Catalysis: Divergent β-H-Elimination Pathways in Repetitive Matsuda–Heck Reactions

“…4-Methoxyphenyltriflate ( 8b ) was synthesized following a literature procedure and its analytical data match those previously described . These arene diazonium salts were synthesized following previously published procedures: 6a – b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k – l , 6m – n , 6o , 6p – q , 6r – 6s , 6t , and 6u . Diazonium salt 6v has been mentioned in the literature, but no synthetic procedure and characterization data were provided.…”

Recent Development of Aryl Diazonium Chemistry for the Derivatization of Aromatic Compounds

“…Moreover, a series of transition-metal-catalyzed, directing group-assisted C–H arylation using aryl diazonium salts have been reported. − Chang described an Ir­(III)-catalyzed ortho -C–H arylation of benzamides with aryl diazonium salts under oxidant-free conditions (Scheme ). Enamides and quinoline N -oxides could also be arylated under these conditions.…”

Recent Progress in Palladium‐Catalyzed Radical Reactions

“…In 2018, Jana et al. described a palladium‐catalyzed ortho ‐C−H arylation for the synthesis of carbazole alkaloids from aniline carbamates and diazonium salts under mild conditions [53] . This transformation showed advantages such as room temperature, no need of any alkali, oxidant, silver or photo redox catalyst, and so on.…”