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Racemic β-hydroxycyclohexanones with up to three chiral centres have been 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 stereoselectivity for an axial hydroxy group in the product β-hydroxycyclohexanones. AM1 calculations show that there is a stabilising electrostatic attraction between the oxygen atom of the axial C-3 hydroxy group and the electron-poor carbon at C-1 in the intermediate oxonium ions. ≥87% of AOC rearrangement occurs via a chair-like transition state giving rise to the 5,6-anti stereochemistry of the β-hydroxycyclohexanones. Trapping the enolate product of AOC rearrangement with oxygen gives fragmentation via a 1,2-dioxetane.

[(6-Methyl-1-oxa-4-thiaspiro[4.5]dec-6-en-7-yl)(allyl)methanols were subjected to anion-accelerated oxy-Cope rearrangement in solvents such as THF, benzene and DME to assess the π-facial selectivity caused by the acetal function. The diastereomeric pairs 17a and 17b (R = Ph) furnished the same two diastereomeric products 18a and 18b, differing only in the relative preponderance. The reaction of 17a turned from mostly syn to oxygen (18a∶18b = 1∶4) in THF to moderately syn to sulfur (18a∶18b = 2.2∶1) in DME. The reaction was completely nonselective in benzene. The effect of solvent on the reaction of 17b was even more interesting. The reaction turned from completely nonselective (18a∶18b = 1∶1) in THF to highly syn to sulfur (18a∶18b = 5.4∶1) in DME. The selectivity in benzene was somewhere in between (18a∶18b = 2.7∶1). Likewise, the reaction of 17b (R = H) turned from moderately syn to oxygen in THF (18a∶18b = 1∶2) to nearly nonselective in DME (18a∶18b = 1∶1.1). The rotation around the bond between the methanol carbon and the adjacent ring-carbon is restricted to allow rearrangement only syn to sulfur in 17a and syn to oxygen in 17b. The considerable erosion in the observed diastereoselectivity is due to a radical and/or ionic retroaldol–recombination process. The radical pathway, however, is more prevalent than the ionic alternative. The recombination favors somewhat the addition of the allyl radical to the cogenerated 7-benzoyl-6-methyl-1-oxa-4-thiaspiro[4.5]dec-6-ene on the face syn to the sulfur. As a result of such dissociation and recombination, the oxy-Cope rearrangement does not appear suitable as a probe for the study of diastereofacial selectivity.

Metallated haloalkenes were used to open epoxides in moderate to good yield. The homoallylic alcohols obtained underwent Swern oxidation to afford three gamma,gamma-difluorinated beta,gamma-enones, which reacted with either vinyllithium,2-lithio-2H-dihydropyran or another metallated haloalkene to afford substituted trans-1,2-divinylcyclohexanols of different degrees of stability. These intermediates underwent neutral thermal oxy-Cope rearrangements when heated in xylene in Ace tubes. The first-formed enols ketonised without loss of HF to afford a range of cyclodecenones in moderate to good yield; X-ray crystallography was used extensively for product characterisation. All substrates rearranged more rapidly than a cis/trans mixture of 1,2-divinylcyclohexanols.

The unsaturated alcohols derived from a ‘one-pot’ tandem [2,3]-Wittig-anionic oxy-Cope (AOC) rearrangement undergo a halocyclisation reaction with iodine in acetonitrile to give substituted tetrahydropyrans with a high degree of stereocontrol.

Thermal oxy-Cope rearrangement of 1,2-divinylcycloalkanols led to ring expansion–cyclopentane annulation; the effect of ring size on the reaction has been studied.

The oxy-Cope rearrangement is utilized for ring expansion of furanosides to chiral hexahydrooxoninones.

The addition of N-methyl-2-pyrrolidone as solvent in the oxy–Cope rearrangement of (3) and (4) increases the yield, and affects the stereoselectivity of the products.

Acetylenic oxy-Cope rearrangement of cyclohex-2-enylprop-2-ynols, a new type of synthetic equivalent of ionone and its analogues, has been investigated in neat and solvent-assisted systems.

Efficient syntheses of the cis-hydrindanones (10) and (14), which are useful as iridoid precursors, are described.