Total Synthesis of 2-Isocyanoallopupukeanane: Construction of Caged Skeleton by Intramolecular Alkylation of Bromonitriles

A new method for constructing the bicyclo[3.2.1]octane skeleton was developed by the intramolecular alkylation of a nitrile-side-chain-containing cyclohexanone derivative. The cyclization precursors were prepared via the stereoselective bromination of the triisopropylsilyl enol ethers of 4-substituted cyclohexanones. Upon treatment with LiNEt2, the bromonitriles underwent a stereoselective intramolecular S(N)2 reaction to afford bicyclo[3.2.1]octane derivatives with a cyano group on the convex face. The total synthesis of 2-isocyanoallopupukeanane (6.5% yield) from methyl vinyl ketone was accomplished via a 17-step transformation.

Automated summary

A new method for constructing the bicyclo[3.2.1]octane skeleton was developed using intramolecular alkylation. The total synthesis of 2-isocyanoallopupukeanane was achieved via a 17-step transformation, showcasing the significance of this synthetic method in constructing complex organic molecules.