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

Abstract

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 LiNEt 2 , 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.

An Enantiospecific Synthesis of Isoneoamphilectane Confirms Its Strained Tricyclic Structure

“…This transformation has been utilized by Wood in the synthesis of kalihinol C as well as by Miyaoka in the synthesis of (±)-7-isocyanoamphilecta-11(20),15-diene . An alternative approach we envisionedwhich had not at the time been applied to the synthesis of ICTsis a hydrogen-atom-transfer-(HAT)-mediated hydroazidation of an alkene. Simple functional group interconversions would transform the tertiary azide to the desired isonitrile.…”

“…This transformation has been utilized by Wood in the synthesis of kalihinol C 40 as well as by Miyaoka in the synthesis of (±)-7-isocyanoamphilecta-11(20),15-diene. 41 An alternative approach we envisioned�which had not at the time been applied to the synthesis of ICTs 42 tertiary azide to the desired isonitrile. We were encouraged by precedence from the groups of Carreira 43 and Boger, 44 each of whom reported conditions for alkene hydroazidation, using cobalt and iron catalysts, respectively.…”

Biomimetic total syntheses of renifolin F and antiarone K

“…Subsequently, our attention is directed towards forming the five-membered core ring via intramolecular ene-type cyclization. Based on literature precedents of closely related systems, 19,20 we initially subjected 14 to thermal conditions at high temperature (toluene, 180 °C) in a sealed tube. The reaction was non-selective and furnished an inseparable 3 : 1 trans/ cis mixture ( 1 H and 13 C NMR, see ESI †) along with a further cyclized product 16, originating from cis-15.…”