Asymmetric Synthesis of <i>gem</i>-Difluoromethylenated Dihydroxypyrrolizidines and Indolizidines

An asymmetric synthesis of <i>gem</i>-difluoromethylenated dihydroxypyrrolizidines and indolizidines is described. The fluoride-catalyzed nucleophilic addition of PhSCF₂SiMe₃ (<b>1</b>) to chiral imides was achieved in satisfactory yields to provide mixtures of <i>syn</i>- and <i>anti</i>-isomers <b>6</b>–<b>9</b> with moderate to good diastereoselectivities. Reductive cleavage of the phenylsulfanyl group followed by intramolecular radical cyclization of the <i>syn</i>-isomers <b>6</b>–<b>9</b> occurred under refluxing conditions to afford the corresponding <i>gem</i>-difluoromethylenated 1-azabicyclic compounds <b>10</b>–<b>13</b> in moderate yields as a separable mixture of <i>cis</i>- and <i>trans</i>-isomers. The <i>cis</i>-isomers of compounds <b>10</b> and <b>12</b> and <i>trans</i>-<b>13</b> were readily transformed to <i>gem</i>-difluoromethylenated dihydroxypyrrolizidines <b>20</b> and <b>27</b> and indolizidine <b>28</b>, respectively, by reductive cleavage of the hydroxyl group and organometallic addition followed by hydrogenolysis.