Atom Economy. Palladium-Catalyzed Formation of Coumarins by Addition of Phenols and Alkynoates via a Net C—H Insertion.

A strategy to achieve ortho substitution of phenols initiated by an ortho-palladation to create\ncoumarins was examined. Indeed, treatment of alkynoates with electron-rich phenols in the presence of a\npalladium catalyst and an acid does generate coumarins. The scope of the reaction with respect to the\nphenol and the alkynoates is defined. With unsymmetrical aromatic substrates, generally good regioselectivity\nthat reflects the HOMO coefficients can be observed. In the course of these studies, numerous important\nnaturally occurring coumarins have been synthesized, including fraxinol methyl ether, ayapin, herniarin,\nxanthoxyletin, and alloxanthoxyletin. The fact that a Pd(0) is the precatalyst rather than a Pd(+2) species\nand that an acid that reduces Pd(+2) salts, formic acid, functions better than other carboxylic acids raises\ndoubts about the initial working hypothesis. A novel mechanism involving a palladium phenoxide formed\nfrom a hydridopalladium carboxylate and phenol is invoked to rationalize the results.