Stereoelectronic Effects in the 6-Exo Free Radical Cyclization of Acyclic Sugar Derivatives: Synthesis of Branched Chain Cyclitols

Article abstract of DOI:10.1021/jo00068a025

The synthesis and free radical carbocyclization (Bu3SnH + AIBN) of acyclic sugar derivatives 1 - 12 is reported.The yields of these 6-exo cyclization processes are good and the diastereomeric excesses are from moderate to excellent.The resulting cyclohexanes are polyoxygenated, enantiomerically pure building blocks for the synthesis of complex branched chain cyclitols.The results obtained in the cyclization of radical precursors 1, 4, 6, and 8 are in sharp contrast with the results observed in the ring closure of compounds 2, 3, 5, and 7.An electron-attracting group (acetate or mesylate), located in a vicinal position to the carbon-centered radical, modifies the conformation of the reacting species in the transition state and thus changes the stereochemical outcome of the cyclization.This allowed us to select the nature of the absolute configuration at the newly formed stereocenter by simply changing the type of the substituents at the vicinal carbon where the radical is generated.