Biaryl Synthesis Via Pd-Catalyzed Decarboxylative Coupling Of Aromatic Carboxylic

The biaryl moiety is an important structural motif in a large number of biologically active compounds and functional molecules, such as natural products, drug intermediates, synthetic dyes, polymers and agricultural drugs. Chemists have always been looking for a simple and effective method which is able to directly couple two aromatic derivatives to synthesize such biphenyl compounds.In the past decades, researchers have found that carboxylic acids can be used not only as the source of aryl electrophile but also as aryl metal when being undergone the decarboxylation procedure for generating aryl-Pd species. Aromatic carboxylic acids, as substrates in coupling reaction, will greatly simplify the preparation of coupling process in this way. Besides, it is an advantage that aromatic carboxylic acids could easily be obtained at low cost in the commercial market. Additionally, the only by-product of decarboxylation procedure is carbon dioxide which is much more environmental friendly compared to the heavy polluting by-products generated from traditional coupling reaction. For these reasons, the development of aromatic carboxylic acids as new substrates of coupling reaction has become a research focus in recent years.This paper explained the author's recent works on these topics, with focus on the development of biaryl synthesis via Palladium-catalyzation.Firstly, the author summarized the recent developments of biaryl synthesis. A general review is provided for reactions catalyzed by Copper, Iridium, Ruthenium, Rhodium and Palladium.Secondly, Palladium-catalyzed decarboxylative coupling reactions were studied. After examining various ratios of reagent, reaction temperature and time, the author has found the optimized reaction conditions for this transformation. With the optimized conditions, several unsymmetrical biaryls products were prepared. The author also investigated the self-coupling reaction of aromatic carboxylic acids decarboxylation in order to produce the symmetric biaryls under similar conditions. Additionally, a possible mechanism was proposed to explain the reaction.Thirdly, this paper introduced the research on N-aryl tetrahydroisoquinolines reaction with methyl ketones via Cu-catalyzation. The author found a relatively optimized reaction conditions for this transformation by comparing and screening various catalysts and solvents. under optimized conditions found, the scope of substrates was investigated and a variety of N-aryl tetrahydroisoquinolines were successfully coupled with different methyl ketones and a possible mechanism was proposed.Through the above works, an efficient Palladium-catalyzed decarboxylative coupling reaction for preparing biaryl from aromatic carboxylic acids has been developed. The procedure shown in this paper extended not only the application scope of Pd-catalysis, but also the application of aromatic carboxylic acids in coupling reaction. In another perspective, the application scope of Mannich reaction via a-C-H bond activation was expanded, providing with an efficient new method of formulating complex and functional molecules.