Gold-Catalyzed Annulations of 2-Alkynyl Benzaldehydes with Vinyl Ethers: Synthesis of Dihydronaphthalene, Isochromene, and Bicyclo[2.2.2]octane Derivatives

With the suitable selection of a gold catalyst as well as the appropriate control of the reaction conditions, various new gold‐catalyzed cyclizations of 2‐alkynyl benzaldehyde with acyclic or cyclic vinyl ethers have been developed. Acetal‐tethered dihydronaphthalene and isochromenes were obtained from the reactions of 2‐alkynyl benzaldehydes with acyclic vinyl ethers under mild conditions. And, more interestingly, the gold‐catalyzed reactions of 2‐alkynyl benzaldehyde with a cyclic vinyl ether afforded the bicyclo[2.2.2]octane derivative involving two molecules of cyclic vinyl ethers. These products contain interesting substructures that have been found in many biologically active molecules and natural products. In addition, a gold‐catalyzed homo‐dimerization of 2‐phenylethynyl benzaldehyde 1 a was observed when the reaction was carried out in the absence of vinyl ether, affording a set of separable diastereomeric products. Plausible mechanisms for these transformations are discussed; a gold‐containing benzopyrylium was regarded as the crucial intermediate by which a number of these new transformations took place. The (mild) Midas touch: The gold‐catalyzed reactions of 2‐alkynyl benzaldehydes with acyclic or cyclic vinyl ethers afforded acetal‐tethered dihydronaphthalene 1, isochromene 2, and bicyclo[2.2.2]octane 3 under mild reaction conditions (see scheme). Plausible mechanisms for the formations of these interesting compounds are discussed.