Synthesis Via Pd-Catalyzed Decarboxylative Coupling Of Aromatic Carboxylic Acid

Pd-catalyzed cross-coupling between aryl halides and aryl metals has becomeone of the most powerful methods for the syntheses of biaryls. However, onefundamental drawback with these coupling reactions is that they require the use of astoichiometric amount of an expensive organometallic reagent that often has to beprepared either beforehand or in situ. Recently, benzoic acids have emerged as viablecoupling partners, largely through the efforts of Goossen and others.What is interesting is that benzoic acids can be used not only as the source ofthe aryl electrophile but also as the aryl metal equivalent after undergoing in situdecarboxylation to generate the aryl-Pd species. As a result, we have decided to developPd-catalyzed couplings that use benzoic acids as substates.In this thesis a series of reactions catalzyled either by Pd or In were studied andthe results are described.In chapter1, a general review on Pd-catalyze decarboxylation coupling, Pd-orCu-catalyzed biphenyl synthesis and In-catalyze carbon-carbon bond-formingreaction was given.In chapter2, we have shown that, using Pd as the catalyst and Ag2CO3as thebase and the oxidant, substituted benzoic acids can be used to arylate thiazoles,benzoxazole and polyfluorobenzenes after in situ decarboxylation. We opted to usethe combination of PdCl2/2PPh3/Ag2CO3as our standard conditions. The reactionoccurs with high chemo-and regioselectivity, representing an excellent alternative tothose Pd-, Ni-, or Cu-catalyzed coupling with aryl halides and sulfonates.In chapter3, we have demonstrated that not only symmetrical but alsounsymmetrical biaryls can be efficiently synthesized through the Pd-catalyzeddecarboxylative homo-or heterocoupling of substituted benzoic acids. Compared tothe traditional route of first converting the acids into amines, followed bydiazotization to form aryl halides, which are then subjected to Ullmann couplingconditions to produce the desired biaryls,this method is much more straightforwardand simple to run, provided that the needed benzoic acid is commercially availableor can be readily synthesized.In chapter4, an efficient Pd-catalyzed decarboxylative coupling reaction forpreparing biaryl from benzoic acid and phenyl boronic acid has been developed. In chapter5, a novel way of converting cyclohexenamides into anilides wasdeveloped with Pd-catalysis using Ag2CO3as the oxidant. The high yield of thereaction was found to be critically dependent on the addition of a catalytic amount ofacid as additive.In chapter6, we have developed a method for the synthesis of tetralin andchromane derivatives via an intramolecular hydroarylation of ω-aryl-1-alkenes viaIn-catalysis. Tetralins and chromanes are important structural motifs and they arepresent in a wide variety of natural products and pharmaceuticals. The use ofcheaper indium salts instead of the expensive noble metal Ru could be advantageouswhen the reaction is run on a large scale. Though narrower in substrate scope, theindium catalyzed reaction could potentially be useful in selected cases andcomplementary to the Ru-catalyzed version.In chapter7, we found that the intramolecular cyclization of aryl halides couldbe mediated by base with the aid of a catalytic amount of1,10-phenanthrolinederivative to from dibenzofurans, carbozole and other heterocyclic compoundsthrough a free radical mechanism. Anhydrous Fe(OAc)2as catalyst can also be used.Through the above works, the scope of Pd-catalyze decarboxylation coupling ofarycarboxylic acids has been greatly expanded, and these transformations can findapplications in the synthesis of natured products, drugs, alkaloids, ligands andbiphenyl liquid crystals, etc.