Tetrasubstituted alkenes are found in a variety of biologically active natural compounds, drugs and functional materials, but methods for their synthesis are limited. Steric congestion around the double bond is problematic for the classic Wittig-type reactions in terms of both substrate scope and stereoselectivity. There has been much recent interest in the use of metal catalysts to activate alkynes towards reaction with nucleophiles, however, a polarity-reversed process — activating a carbon electrophile towards reaction with an alkyne — which looks reasonable on paper, has not received the same attention. Now, Matthew Gaunt and co-workers from the University of Cambridge have reported a copper(i) catalysed addition of diaryl- or vinyl(aryl)iodonium triflates to alkynes.
Gaunt and co-workers have previously shown copper catalysts could activate diaryliodonium salts towards reaction with π-electron-rich nucleophiles such as indoles or anilines and wondered if this could be extended to reaction with alkynes. It is believed that the hypervalent iodine reagent reacts with the copper catalyst to give a Cu(iii) complex, which then reacts with the alkyne to give a vinyl copper triflate intermediate. Reductive elimination would then return the copper(i) catalyst and produce the vinyl triflate product. In general, disubstituted alkynes react to produce Z-alkenes. And addition to unsymmetrical alkynes proceeds with useful regioselectivity when the substituents are sterically or electronically differentiated. Despite some potential pitfalls, terminal alkynes and even acetylene itself were also shown to be suitable substrates for the reaction. As yet, only a few examples are described involving transfer of an aryl group (rather than vinyl) from the iodonium reagent — which may be due to the need to synthesize the iodine reagents, or perhaps to a problem in controlling which of two groups is transferred to the copper catalyst.
The synthetic utility of the vinyl triflate products is unquestionable as they were then shown to undergo a wide variety of palladium-catalysed cross-coupling reactions. Suzuki and Sonagashira couplings gave alkenes with four carbon substituents, and Buchwald–Hartwig type amination and Miyaura borylation gave amido alkenes and alkenyl boronic esters, respectively, and all without loss of isomeric purity of the alkene.
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Davey, S. Activating iodoniums. Nature Chem 5, 443 (2013). https://doi.org/10.1038/nchem.1674