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 omega-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 afford enantiomerically pure alpha-hydroxy-, alpha-hydroxy-Delta 3,4-, alpha,beta,gamma-trihydroxy-, and alpha-hydroxy-beta,gamma-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.