Palladium(II)-catalysed cycloalkenylation (Saegusa-Ito cyclisation) has been used for the first time to transform difluorinated silylenol ethers to difluorinated cycloalkenones under mild conditions. The silylenol ether precursors were prepared in two high-yielding steps from trifluoroethanol, and cyclised in moderate to good yields. A combination of air and copper(I) chloride in acetonitrile achieved the turnover of the initial palladium(II) salt, while the provision of an oxygen atmosphere ensured more rapid reaction. Annulations required a minimum level of substitution on the chain, but failed when the alkene was substituted. Annelations allowed a range of n,6-bicyclic systems to be prepared and afforded three products in which heterocycles were fused to the new cyclohexenone. The least substituted system explored underwent cyclisation followed by terminal oxidation to a cyclic enal, which corresponded to a Wacker product of unusual regiochemistry.
- homogeneous catalysis
Percy, J. M., McCarter, A. W., Sewell, A. L., Sloan, N., Kennedy, A. R., & Hirst, D. J. (2015). Developing the Saegusa-Ito cyclisation for the synthesis of difluorinated cyclohexenones. Chemistry - A European Journal, 21(52), 19119–19127. https://doi.org/10.1002/chem.201503653