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

Racemic beta -hydroxycyclohexanones with up to three chiral centres have be en synthesized in a stereocontrolled way using the novel anionic oxy-Cope ( AOC) rearrangement of acyclic enol ethers. The first examples of compounds containing an aldehyde and an enol ether in a 1,5 relationship are reported . Stereocontrol in the cyclisation of these compounds by a 6-(enolendo)-exo -trig intramolecular aldol reaction has been studied: there is high stereos electivity for an axial hydroxy group in the product beta -hydroxycyclohexa nones. AM1 calculations show that there is a stabilising electrostatic attr action between the oxygen atom of the axial C-3 hydroxy group and the elect ron-poor carbon at C-1 in the intermediate oxonium ions. greater than or eq ual to 87% of AOC rearrangement occurs via a chair-like transition state gi ving rise to the 5,6-anti stereochemistry of the beta -hydroxycyclohexanone s. Trapping the enolate product of AOC rearrangement with oxygen gives frag mentation via a 1,2-dioxetane.