Palladium-Catalyzed Chelation-Assisted C-H Functionalization of Quinoline Aldehydes to Esters with Mechanistic Insights

Abstract

We have developed a palladium-catalyzed method for the direct coupling of quinoline-8-carboxaldehyde with aliphatic 1 o , 2 o alcohols and phenols to produce quinoline-8-carboxylate. A catalytically active palladacyclic dimer intermediate has been identified by X-ray crystallography, as a key component in the process. This approach enabled the synthesis of a diverse array of quinolinyl esters in good to excellent yields, demonstrating remarkable tolerance for a wide range of functional groups.The ester functional group represents one of the most common motifs in numerous drug molecules, fragrances, agrochemicals, natural products, and building blocks of organic materials. 1 Esters serve diverse industries including pharmaceuticals, biodiesel fuels, food flavorings, 2 cosmetics, soaps, deodorants, and toothpaste fragrances. Given their importance in medicinal chemistry, daily life, and essential applications, the development of efficient synthetic protocols for esterification remains a high-priority target in modern organic synthesis. There are many different methods for ester synthesis, most commonly proceeding through the reaction of alcohols with carboxylic acids or their activated derivatives. 3 One of the most interesting and direct approaches is conversion of aldehydes to esters with an alcohol. The most widely investigated aldehydeto-ester conversion occurs in the presence of alcohol via three repre-sentative approaches: (1) oxidative transformation of aldehydes to esters using stoichiometric oxidants e.g. V2O5-H2O2, oxone, etc 4 (2) NHC-catalyzed activation followed by esterification with alcohols is presence of oxidants; 5 (3) transition metals (e.g. Ir, Rh, Ru) with external/internal Scheme 1: Palladium catalysed and C-H functionalization of quinoline-8carbaldehydes.