Stereocontrol in a one-pot procedure for anionic oxy-Cope rearrangement followed by intramolecular aldol reaction

摘要

Racemic β-hydroxycyclohexanones with up to three chiral centres have been synthesized in a stereocontrolled waynusing the novel anionic oxy-Cope (AOC) rearrangement of acyclic enol ethers. The first examples of compoundsncontaining an aldehyde and an enol ether in a 1,5 relationship are reported. Stereocontrol in the cyclisation of thesencompounds by a 6-(enolendo)-exo-trig intramolecular aldol reaction has been studied: there is high stereoselectivitynfor an axial hydroxy group in the product β-hydroxycyclohexanones. AM1 calculations show that there is a stabilisingnelectrostatic attraction between the oxygen atom of the axial C-3 hydroxy group and the electron-poor carbon at C-1nin the intermediate oxonium ions. ≥87% of AOC rearrangement occurs via a chair-like transition state giving rise tonthe 5,6-anti stereochemistry of the β-hydroxycyclohexanones. Trapping the enolate product of AOC rearrangementnwith oxygen gives fragmentation via a 1,2-dioxetane.