Study On The Domino Reaction Of Oxidative Decarboxylation/Heteroaryl Migration/Remote Fluorination

The high electronegativity of the fluorine atom makes fluorine-containing compounds have unique physical,biological,and chemical properties.Fluorine-containing organic compounds are widely used in pharmaceuticals,agrochemicals,and advanced materials.The introduction of fluorine atoms into a molecule increases the bioavailability,lipophilicity,and metabolic stability of compounds.Therefore,it is valuable to develop new methods for the direct introduction of fluorines,which has been a hot topic for a long time in modern organic synthesis.Carboxylic acids and their derivatives are widely found in nature and have a wide range of sources.Carboxylic acids are widely used in biological and chemical syntheses as one of the most fundamental and important platform molecules because they are readily available and stable.Decarboxylative functionalizations of carboxylic acids are an important class of organic reactions,in which the C-CO2H structural unit undergoes a C-C bond cleavage to liberate one equivalent of carbon dioxide and generate a carbon-centered radical.Compared with traditional cross-coupling reactions,decarboxylation reactions generally do not require toxic,unstable,or potentially dangerous organometallic reagents,and the by-product is non-polluting carbon dioxide gas.In recent years,silver-catalyzed decarboxylation of aliphatic carboxylic acids has received considerable attention.In this dissertation,a silver-catalyzed oxidative decarboxylation/heteroaryl migration/remote fluorination of aliphatic carboxylic acids was first achieved,thus providing a variety of fluorine-containing heteroaryl compounds.The optimized reaction conditions were established by examining the reaction parameters such as catalysts,solvents,and temperature.The reaction was performed with aliphatic carboxylic acids as the substrates,silver nitrate as the catalyst,cheap and stable selectfluor as the fluorinating reagent,and acetone/water as the solvent at 40? for 24 hours.Substrate scope was next investigated under the optimized reaction conditions.It was found that a wide range of fluorine-containing products can be obtained in good yields.All products obtained are new compounds which are not reported in previous literatures.The products were well characterized by 1H NMR,13C NMR,19F NMR,and high resolution mass spectrometry(HRMS).To understand the reaction mechanism,several control experiments were carried out.Based on the preliminary mechanistic investigations and the relevant reports,a plausible reaction mechanism was also proposed..