Decarboxylative C-H Cross-Coupling of Azoles

摘要

The use of carboxylic acids as functional handles for transition metal catalyzed cross-coupling reactions is a fast growing area of research. Pioneering work has established that metal-mediated decarboxylation affords organometallic intermediates that can participate in palladium-catalyzed C-C bond-forming processes such as the Heck reaction and cross-coupling reactions with aryl halides (Steglich, Miura, Goossen, and Forgione). The concept has recently been extended to the C-H activation field. Glorius and coworkers have demonstrated the intramolecular decarboxylative C-H activation of ortho-phenoxy benzoic acids for the synthesis of dibenzofurans, whereas Crabtree and co-workers and Larrosa and co-workers have described the intermo-lecular cross-coupling of ortho-substituted benzoic acids with anisole and indoles, respectively. The union of two emerging areas of catalytic C-C bond-forming chemistry, both of which eschew preformed organometallic substrates, holds great potential for new bond-forming strategies in synthesis. The reaction would be particularly powerful for the synthesis of polyheteroaromatic compounds. The regiocon-trolled union of heteroaromatics, requiring no significant prefunctionalization and proceeding under catalytic condi-tions, could lead to dramatically streamlined syntheses of this fundamental compound class. To investigate this possibility, we have developed an intermolecular decarboxylative C-H cross-coupling between oxazoles and thiazoles with the rapid synthesis of functionalized polyazoles.