Synthesis of Enantiomerically Pure gem-Difluorocyclohexane Derivatives by Intramolecular Trapping of α,α-Difluoroalkyl Radicals

Article abstract of DOI:10.1021/jo00091a041

gem-Difluorocyclohexanols 7 and 16 bearing, respectively, the arylsulfinyl and the arylthio substituent are obtained by radical-promoted cyclization from the corresponding ω-chlorodifluoroheptenols 6 and 9 in good yields.Intermediates 6 are made available by condensing the lithium derivative of chiral arylsulfinyl pentene 4 on ethyl chlorodifluoroacetate and by reducing the carbonyl with hydride-releasing agents.Elimination of the chiral auxiliary sulfinyl group and appropriate elaborations afforded enantiomerically pure α-hydroxy-, α-hydroxy-Δ3,4-, α,β,γ-trihydroxy-, and α-hydroxy-β,γ-epoxy-gem-difluorocyclohexane derivatives 19, 21, 22, and 23.Absolute and relative configurations as well as preferred conformations in solution are given.The degree of asymmetric induction during the radical-promoted cyclization is correlated with the relative configuration of substituted carbons in open-chain compounds.