Photoredox-Catalyzed Decarboxylative Coupling Using Carboxylic Acids And Their Derivatives

The decarboxylative coupling reactions provide powerful methods for the construction of C-C and C-Y(Y = non-carbon atom)bonds.In the first chapter,the development history and current situation of decarboxylative coupling reactions have been reviewed,including transition-metal-catalyzed decarboxylative coupling reactions and visible-light-induced photoredox-catalyzed decarboxylative coupling reactions.Based on the development of transition-metal-catalyzed decarboxylative coupling in the past 15 years,decarboxylative couplings catalyzed solely by a Pd,Cu,Ag,Au,Rh catalyst or by bimetallic catalytic systems,such as Pd/Cu and Pd/Ag,in which a metal cocatalyst is used to facilitate decarboxylation,have been developed to construct C-C,C-N,C-S,C-P,and other bonds.However,these catalytic systems often need a high temperature to meet the energy required for decarboxylation.For example,the reaction temperature of Pd-catalyzed decarboxylative coupling is generally above 120?,which hinders the development and application of the reaction.And the reactions are mainly concentrated on the activated aryl carboxylic acids,alkenyl carboxylic acids,alkynyl carboxylic acids and other non-aliphatic carboxylic acids,only a few examples for the aliphatic carboxylic acids.So a new catalytic system is urgently needed to solve these problems.The visible-light-induced decarboxylative coupling reported in recent years is very mild,in which the radical decarboxylation was successfully achieved by a single electron transfer between the excited photoredox catalyst and the carboxylate anion.The introduction of photoredox catalysis may provide new opportunities for the development of decarboxylative coupling.In addition to the mild conditions and excellent compatibility,photoredox catalysis can also be combined with the transition-metal catalysis to solve the problem that was not easy to solve.In the second chapter,enabled by merging iridium-catalyzed photoredox catalysis and palladium catalysis,?-oxocarboxylate salts can be decarboxylatively coupled with aryl halides to generate aromatic ketones and amides at room temperature under mild conditions The reaction utilizes both the decarboxylation ability of photoredox catalysis and the bonding ability of palladium catalysis.This dual catalytic system solved the problem of high temperature required for traditional Pd-catalyzed decarboxylative coupling.The reaction has excellent compatibility and can provide an effective method for the synthesis of ketones and amides.Direct C-H alkylation of N-heteroarenes is an important transformation of considerable interest in the pharmaceutical industry due to the prevalence of functionalized N-heteroarenes found in medicinal compounds.The well-established Minisci reaction is a useful method to accomplish this task,in which a strong oxidative condition is used for the radical decarboxylation.However,the presence of strong oxidant makes the reaction incompatible with functionalities that are easily oxidized,and always generates a variety of radical-addition by-products.In the third chapter,we achieved a photoredox-catalyzed redox-neutral Minisci-type decarboxylative alkylation using redox-active esters as alkylation reagents under visible light irradiation.The reaction provides a mild and effective strategy for C-H alkylation of N-heteroarenes.The reaction utilizes photoredox catalysis to achieve the radical decarboxylation without the need of a stoichiometric amount of oxidant.Thus,Functionalities that are sensitive to strong oxidants,such as aldehyde,alkene,and sulfide,can be tolerated.The traditional Minisci reaction is inefficient when a-aminoalkylation of N-heteroarenes is required due to the ease of overoxidation of an a-aminoalkyl radical,generated from the radical decarboxylation under a strong oxidative condition,to the iminium cation,removing its nucleophilicity.In the fourth chapter,enabled by merging iridium photoredox catalyst with a phosphate acid catalyst,we achieved the C-H ?-aminoalkylation of N-heteroarenes using amino acid and peptide redox-active esters as a-aminoalkylation reagents.In addition to various natural and unnatural amino acids,the peptides are also the appropriate substrate.Moreover,the reaction can achieve the derivatization of various complex N-heteroarenes due to the mild conditions.We have solved some difficult problems in the decarboxylative coupling reactions by using the photoredox catalysis,enriched the type of decarboxylative coupling reaction,and promoted the application of photoredox catalysis in the decarboxylation coupling.Of course,some problems still exist,efforts will be devoted to overcome these difficulties.