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

gem-Difluorocyclohexanols 7 and 16 bearing, respectively, the arylsulfinyl and the arylthio substituent are obtained by radical-promoted cyclization from the corresponding o-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 hydridereleasing agents. Elimination of the chiral auxiliary sulfinyl group and appropriate elaborations afford enantiomerically pure a-hydroxy-, a-hydroxy-A3,4-, a,&y-trihydroxy-, and a-hydroxy-(?,yepoxy- 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.