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

Arghya Polley,Kasarla Varalaxmi,Ranjan Jana

doi:10.1021/acsomega.8b02009

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.

Highlights

They have been used extensively in Heck−Matsuda arylation of alkenes, they have not been explored much in C− H arylations.2−6 This could be attributed due to the fact that oxidative addition of metal complex to the diazonium salts is extremely facile, whereas C−H insertion proceeds through a high energetic pathway at a sluggish reaction rate7,8 because the differentiation in the kinetics of deleterious side product such as homocoupling formation becomes predominant
We report a palladium-catalyzed ortho C−H arylation of aniline carbamates with inexpensive and readily available aryldiazonium salts at room temperature
We anticipated that because of the electron-donating nature of the N,N-dimethyl group, the ortho-position becomes highly electron-rich for uncontrolled electrophilic palladation

Summary

Introduction

Aryldiazonium salts are a viable surrogate to the conventional aryl halides and oxygen-based electrophilic coupling partners. they have been used extensively in Heck−Matsuda arylation of alkenes, they have not been explored much in C− H arylations.− This could be attributed due to the fact that oxidative addition of metal complex to the diazonium salts is extremely facile, whereas C−H insertion proceeds through a high energetic pathway at a sluggish reaction rate because the differentiation in the kinetics of deleterious side product such as homocoupling formation becomes predominant. Aryldiazonium salts are a viable surrogate to the conventional aryl halides and oxygen-based electrophilic coupling partners.. Aryldiazonium salts are a viable surrogate to the conventional aryl halides and oxygen-based electrophilic coupling partners.1 They have been used extensively in Heck−Matsuda arylation of alkenes, they have not been explored much in C− H arylations.− This could be attributed due to the fact that oxidative addition of metal complex to the diazonium salts is extremely facile, whereas C−H insertion proceeds through a high energetic pathway at a sluggish reaction rate because the differentiation in the kinetics of deleterious side product such as homocoupling formation becomes predominant. The Chang group has reported an highly reactive iridium(III)-catalyzed C−H arylation of benzamides with aryldiazonium salts.. Palladium and photoredox dual catalysis has been explored, only palladiumcatalyzed C−H arylation of aniline carbamates with aryldiazonium salt is not known. As a part of our research program in C−H functionalization, we have accomplished the synthesis of indoles and indolines from aryl urea through C−H activation at room temperature. On the other hand, we have performed

Methods

Results

Conclusion