Clauszoline K

Palladium-Catalyzed Ortho C-H Arylation of Aniline Carbamates with Diazonium Salts under Mild Conditions: Expedient Synthesis of Carbazole Alkaloids.[Pubmed:31458136]

ACS Omega. 2018 Oct 31;3(10):14503-14516.

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.

A Palladium-Catalyzed Ullmann Cross-Coupling/Reductive Cyclization Route to the Carbazole Natural Products 3-Methyl-9H-carbazole, Glycoborine, Glycozoline, Clauszoline K, Mukonine, and Karapinchamine A.[Pubmed:28225623]

J Org Chem. 2017 Apr 21;82(8):4148-4159.

The title natural products 2-7 have been prepared by reductive cyclization of the relevant 2-arylcyclohex-2-en-1-one (e.g. 20) to the corresponding tetrahydrocarbazole and dehydrogenation (aromatization) of this to give the target carbazole (e.g. 4). Compounds such as 20 were prepared using a palladium-catalyzed Ullmann cross-coupling reaction between the appropriate 2-iodocyclohex-2-en-1-one and o-halonitrobenzene.

Clauszoline K (CAS 187110-71-0) is a natural product offered by BioCrick for research applications. Customers can buy or order Clauszoline K from BioCrick, a supplier and manufacturer of research chemicals, with product specifications, purity, packaging, and pricing information available upon request.