Gold- or Silver-Catalyzed Syntheses of Pyrones and Pyridine Derivatives: Mechanistic and Synthetic Aspects

3‐Oxo‐5‐alkynoic acid esters, on treatment with a carbophilic catalyst, undergo 6‐endo‐dig cyclization reactions to furnish either 2‐pyrones or 4‐pyrones in high yields. The regiochemical course can be dialed in by the proper choice of the alcohol part of the ester and the π‐acid. This transformation is compatible with a variety of acid‐sensitive groups as witnessed by a number of exigent applications to the total synthesis of natural products, including pseudopyronine A, hispidine, phellinin A, the radininol family, neurymenolide, violapyrone, wailupemycin and an unnamed brominated 4‐pyrone of marine origin. Although the reaction proceeds well in neutral medium, the rate is largely increased when HOAc is used as solvent or co‐solvent, which is thought to favor the protodeauration of the reactive alkenyl‐gold intermediates as the likely rate‐determining step of the catalytic cycle. Such intermediates are prone to undergo diauration as an off‐cycle event that sequesters the catalyst; this notion is consistent with literature data and supported by the isolation of the gem‐diaurated complexes 12 and 15. Furthermore, silver catalysis allowed access to be gained to 2‐alkoxypyridine and 2‐alkoxyisoquinoline derivatives starting from readily available imidate precursors. Dial‐in: Upon proper choice of the ester terminus and the carbophilic catalyst, readily accessible 3‐oxo‐5‐ynoate derivatives are converted either into 4‐hydroxy‐2‐pyrones or 2‐alkoxy‐4‐pyrones, as one desires. The conditions are unusually mild, as witnessed by a number of applications to delicate natural products. The underlying concept has also been extended to the preparation of N‐heterocycles such as 2‐alkoxypyridines or ‐isoquinolines.