Pd/C-Catalyzed Suzuki Reaction Involving Tetraarylborates And Its Application In Drug Syntheses

The study for the formation of aryl-aryl bond has become one of the most important aspects in modern organic syntheses. The Suzuki cross-coupling reaction catalyzed by palladium can effectively construct biaryl fragments. Recently, the high reactivity of tetraarylborates for Suzuki reaction has been found. However, as a relatively stable, easily removable, inexpensive and reusable heterogeneous catalyst, palladium charcoal-catalyzed Suzuki reaction involving tetraarylborates has not yet been reported.We first reported this type of coupling reaction in this thesis. The reactions of sodium tetraphenylborate (2a) or tetrakis(4-tolyl)borate (2b) with various bromoaryl carboxylic acids or phenols (1a-j) were carried out, and the effects such as catalyst amount, type of inorganic bases were discussed in detail. Fourteen biaryl compounds (3a-j, 4a-d) were synthesized and characterized by elemental analyses, ¹H NMR and ¹³C NMR. All yields were determined by HPLC analyses. These reactions, performed in pure water under air in excellent yields without using any phosphine ligands or additives, would be suitable for bulky syntheses by using this reusable and cheap catalyst.Based upon the results found in the coupling of 6-bromo-2-naphthoic acid (1a) or 4-bromophenol (1j) with sodium tetraphenylborate (2a) in the presence of different amounts of base, we depicted here a concise mechanism consisting of four catalytic cycles for this Pd (0)-catalyzed coupling reaction. The separation and analyses of the two generated by-products, phenylboronic acid and benzene, from the reaction mixture in the absence of any added base further clarified this proposed mechanism.In terms of green chemistry, this new synthetic strategy was successfully applied to the syntheses of Felbinac (5), Fenbufen (6) and Flurbiprofen (7), three nonsteroidal anti-inflammatory drugs (NSAIDs) bearing biaryl fragments.To the best of our knowledge, these studies have not yet been reported in literatures.