Abstract
The presence of the amide functional group in several important compounds, with various application has led to the development of various methods in accessing these amides. Traditional amidation protocols rely on the use carboxylic acids and a suitable amine as coupling partners in the presence of an activating agent. These activating agents are often of large molecular weight and used in excess amounts, thus, generating large quantities of undesired by-products. As a result, the amide coupling reaction has been identified as one of the key areas for green chemistry research and development. Various protocols have been developed to access the amide bond from different functional groups including esters, aldehydes, ketones, alcohols, nitriles and other existing amides with suitable coupling substrates. One approach that has recently gained attraction is the use of nitroarenes arylamine surrogates, thus, enabling an access to amides in a step-economic pathway. Nitroarenes, are cheaper than their amine analogues, they are also stable and are useful for late-stage organic transformations. Furthermore, they have been demonstrated as suitable coupling partners in reductive aminocarbonylation reaction with acyl donors such as carboxylic acids, esters, aldehydes, and carbon monoxide to mention a few. However, the substrate scope has not been fully explored, thus, there is an opportunity to broaden the scope. Herein, we expand on the versatility of this amide synthesis procedure by exploring a palladium metal-catalyzed reductive aminocarbonylation of aryl halides with nitroarenes. Reaction optimization studies included the investigation of parameters such as solvent options, reaction temperature, base, palladium and ligand catalysts, as well as reduction additives. The optimized model reaction afforded the desired product yield up to 92%. Substrate scope studies revealed that the reaction afforded products from low to appreciable yields with a wide variety of nitroarenes, aryl bromides and iodides. Activation of aryl chlorides proved to be a challenge under the developed reaction conditions and will need further optimization...
M.Sc. (Chemistry)