Pd/pivalic acid mediated direct arylation of 2-pyrones and related heterocycles

Abstract Direct arylation represents a favourable alternative to traditional cross-coupling reactions and has found widespread use with simple aryls and robust heterocycles. Herein a direct arylation protocol has been optimised and applied to more delicate, privileged biological motifs. The intramolecular direct arylation of 2-pyrones, 2-coumarins, 2-pyridones and 2-quinolones occurs in very good to excellent yields using a Pd⁰ source and pivalic acid as a crucial additive. Preliminary mechanistic investigations were also carried out. Direct Arylation represents a favourable alternative to traditional cross-coupling reactions. However there are limited reports on application to more delicate, privileged biological motifs. Herein the intramolecular Pd/PivOH promoted direct arylation of 2-pyrones, 2-coumarins, 2-pyridones and 2-quinolones is reported. One intermolecular example is included along with preliminary mechanistic investigations.