Conformation and Reactivity of Anomeric Radicals

Article abstract of DOI:10.1021/ja00048a005

Reductive decyanations of 2-cyanotetrahydropyran derivatives with sodium in ammonia show a strong preference for axial protonation.For the 2-cyanotetrahydropyran 6, the selectivity is 119:1, and for the cyanooxadecalin 13, which is sterically biased against axial hydrogen introduction, the ratio is 1.78:1.These stereochemical outcomes and ab initio calculations of the intermediate radical conformations are consistent with the following mechanistic model: reductive decyanation proceeds through the pyramidal, axial radical to give the configurationally stable, contrathermodynamic axial anion which is protonated with retention of configuration.Anomeric carbohydrate radicals have been described as nearly planar on the basis of electron spin resonance (ESR) spectroscopic studies, and that observation appears to be inconsistent with this model.Ab initio calculations show that though the pyramidalization at the radical center is small, the potential surface for pyramidalization is very asymmetric.Examination of the energy surface for the 2-tetrahydropyranyl radical 17 shows a 3.46 kcal/mol energy difference at UMP2/6-31G^*//6-31G^* on going from the axial ( Θ = -139.5 deg) to the equatorial ( Θ =149.5 deg) conformer.The UMP2/6-31G^*//6-31G^* calculated energy differences between axial and equatorial conformers for tetrahydropyranyl radical 18 and oxadecalinyl radical 22 are qualitatively consistent with the experimentally observed reductive decyanation product ratios.The semiempirical methods AM1 and PM3 poorly model anomeric stabilization in radicals and are not useful for predicting radical conformations.Calculations show that introduction of an electron-withdrawing substituent, fluorine, in the equatorial 3-position of the tetrahydropyran radical 21c flattens the radical center and makes the boat conformation 21b more accessible, in good agreement with the substituent effects found in ESR studies of carbohydrate radicals.