Pd-catalysed regioselective C-H functionalisation of 2-pyrones

Functionalised 2-pyrones (2H-pyran-2-ones) have attracted considerable interest as medicinal agents, natural products, fluorescent derivatives, and synthetic intermediates.(1) Classical cross-coupling reactions (e. g. Negishi,(2) Stille(3) and Suzuki-Miyaura(4) and others(5)) provide convenient access to these targets. However, there is strict requirement for the 2-pyrone to be appropriately prefunctionalised, either as the organometallic 'nucleophilic' component or the halide/pseudohalide 'electrophilic' component. It has been argued(6) that a more efficient process would involve the union of two reaction components possessing C H and C X bonds, respectively. For several heteroaromatic compounds, this has been possible, and indeed some very efficient methods have been developed.(7) However, surprisingly there are no reported catalytic methods involving the C-H functionalisation of 2-pyrones.(8) We are engaged in the development of innovative synthetic methods geared towards 2-pyrones and their metal complexes.(9) We report herein the intramolecular Pd-catalysed C-H functionalisation of 2-pyrones, which is regioselective.