Silver(I)-Mediated Decarboxylative Transformations; Benzoic Acids as Aryl Donors in Organic Synthesis.

Abstract

The use of aromatic carboxylic acids as coupling agents in cross-coupling reactions has arisen in the past few years as a very useful tool for organic chemists. The generation of CO2 as the main byproduct has placed this novel approach amongst the greenest alternatives to the traditional cross-couplings, where stoichiometric metal salt waste is usually generated. This thesis contains the study of a novel decarboxylative approach towards the synthesis of C–C bonds for the formation of biaryl structures based on Ag(I) salts. The introduction contains an overview of the recent developments that have appeared in the literature concerning this novel mode of activation, and a discussion on how decarboxylative transformations have given rise to powerful methodologies involving high atom and step economy. This thesis starts describing the development of the first intermolecular decarboxylative direct arylation protocol. Such methodology was applied to the direct arylation of indoles using benzoic acids as coupling partners. This reaction proceeds in a regioselective fashion giving exclusively the arylated product at the C3 position. Moreover, the use of catalytic amounts of Ag(I) salts were found to efficiently protodecarboxylate a wide range of benzoic acids bearing electron-withdrawing or electron-donating groups at the ortho position. In addition, such protocol was applied to heteroaromatic acids bearing α heteroatoms to the carboxylic acid. (Hetero)aromatic carboxylic acids were also proven to be suitable candidates to perform decarboxylative homocoupling to give good yields of the dimers. Further to the Ag(I)-mediated decarboxylative methodologies, Au(I) salts were also found to undergo decarboxylation of (hetero)aromatic carboxylic acids providing a wide range of stable aryl-gold(I) compounds with excellent yields. Finally, the first methodology for a meta-selective direct C–H arylation using iodoarenes as coupling partners is also reported. This process, which is compatible with a wide range of meta substituents, utilises carboxylic acids as traceless directing groups affording complete control upon the regioselectivity of the direct C–H arylation.