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

Abstract

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.

Silver‐Catalysed Domino Approach to 1,3‐Dicarbo‐Substituted Isochromenes

“…As previously observed,, the formation of dimers 3 can been ascribed to the silver‐catalysed addition of water to the triple bond of the 2‐alkynyl(hetero)arylaldehyde 1 , or to the respective organosilver isochromenylium intermediate, to generate a ketone, which, in the enol form, attacks, as a nucleophile, a second electrophilic isochromenylium intermediate. Nevertheless, when we tried to perform the reaction in strongly anhydrous conditions (under nitrogen and in the presence of 4 Å molecular sieves), we observed that the reaction was totally hampered and the starting material was almost quantitatively recovered.…”

“…A fast protodemetallation, may be assisted by the acidic proton of the nucleophile, leads to the 1‐acyl‐substituted isochromene 2 and regenerates the catalyst. Alternatively, following path B, the isochromenylium ( I ) can be hydrated to give the keto aldehyde ( IV ),, which then attacks as a nucleophile a second isochromenylium intermediate ( I ) to yield the dimeric compound 3 . Thus, in this cascade process the silver catalyst plays a dual role: 1) as a π‐philic activator of the triple bond able to promote the formation of the isochromenylium intermediate ( I ) and 2) as a σ‐philic activator of the carbonyl oxygen able to promote a fast keto–enolic equilibria in the ketone.…”

Six-Membered Ring Systems

“…The high enantioselectivity results from the combination of axially chiral diphosphine(AuCl) 2 precatalysts and silver salt cocatalysts (Scheme 38) (13JOC10986). A gold(III) catalyst promotes the annulation of 2-alkynyl benzaldehydes with ethyl vinyl ether in the presence of an alcohol to afford a range of 1H-isochromenes (13CEJ4043). High yields of 1H-isochromenes result from the intramolecular oxycupration of allenes and subsequent asymmetric addition of the in situ-generated allylcopper species to carbonyl compounds, with excellent enantioselectivity (Scheme 39) (13AGE7177).…”

Isoquinolone Synthesis via Zn(OTf)2-Catalyzed Aerobic Cyclocondensation of 2-(1-Alkynyl)-benzaldehydes with Arylamines

“…Among the different protocols for achieving this goal, the synthetic strategies starting from 2-(1-alkynyl)benzaldehydes are the most interesting due to their high atom utilization [15,21] (Scheme 1). Although the readily available 2-(1-alkynyl)benzaldehydes have been well-applied in the synthesis of benzo-fused six-membered heterocycles [27][28][29][30][31][32][33] and carbocycles [34][35][36][37][38][39], their applications for isoquinolone synthesis are very rare. As shown in Scheme 1, only two procedures have been reported to approach isoquinolones from the direct intermolecular cyclocondensation of 2-(1-alkynyl)-benzaldehydes with primary amines.…”