Nickel-Catalyzed Domino Cross-Electrophile Coupling Dicarbofunctionalization Reaction To Afford Vinylcyclopropanes

We have established a nickel-catalyzed domino reaction that harnesses sulfonamide, alkyl chloride, and alkyne fuuctionalities in a multistep sequence to afford vinylcyclopropanes bearing tetrasubstituted olefins. The starting materials are prepared by iron-promoted aza-Prins reactions of ynals. This method provides rapid synthetic access to valuable building blocks with applications in medicinal chemistry. Experimental and computational results support the initiation of the catalytic cycle by oxidative addition of the propargylic sulfonamide, and a key ambiphilic allenylnickel intermediate leads to a bifurcated reaction pathway that generates olefin isomers.

Automated summary

A nickel-catalyzed domino reaction has been developed that utilizes sulfonamide, alkyl chloride, and alkyne functional groups to synthesize novel compounds with valuable applications in medicinal chemistry. The method involves a multistep sequence starting from ynals through iron-promoted aza-Prins reactions, leading to the formation of vinylcyclopropanes bearing tetrasubstituted olefins. Experimental and computational results support the proposed mechanism of the catalytic cycle, with a key ambiphilic allenylnickel intermediate leading to a bifurcated reaction pathway that generates olefin isomers.